Pub Date : 2024-04-02DOI: 10.1186/s12645-024-00257-3
Ye Tao, Zhongping Chen
Effective drug delivery of nanomedicines to targeted sites remains challenging. Given that hypobaric hypoxia and hyperbaric oxygen exposure can significantly change pharmacokinetics of drugs, it is interesting to determine whether they can regulate tissue distribution of nanomedicine, especially in tumor, for enhanced cancer therapy. Hypobaric hypoxia exposure improved the pharmacokinetics of paclitaxel-loaded liposomes and facilitated their distribution in the heart and liver, whereas hyperbaric oxygen exposure did not benefit and even impaired the pharmacokinetics and distribution. Particularly, both hypobaric hypoxia and hyperbaric oxygen exposure could not improve the distribution in subcutaneous tumor. Thus, we constructed orthotopic liver tumor model and discussed whether high distribution of the liposomal nanomedicine in the liver, facilitated by hypobaric hypoxia exposure, could ensure their effective accumulation in liver tumor for enhanced cancer therapy. The liposomal nanomedicine with adjuvant hypobaric hypoxia exposure significantly inhibited the growth of orthotopic liver tumor for prolonged survival time, achieved by hypobaric hypoxia-promoted accumulation at tumor sites of the liver. It might be the first example of the application of adjuvant intermittent hypobaric hypoxia exposure in treating liver cancer.
{"title":"Hypobaric hypoxia exposure regulates tissue distribution of nanomedicine for enhanced cancer therapy","authors":"Ye Tao, Zhongping Chen","doi":"10.1186/s12645-024-00257-3","DOIUrl":"https://doi.org/10.1186/s12645-024-00257-3","url":null,"abstract":"Effective drug delivery of nanomedicines to targeted sites remains challenging. Given that hypobaric hypoxia and hyperbaric oxygen exposure can significantly change pharmacokinetics of drugs, it is interesting to determine whether they can regulate tissue distribution of nanomedicine, especially in tumor, for enhanced cancer therapy. Hypobaric hypoxia exposure improved the pharmacokinetics of paclitaxel-loaded liposomes and facilitated their distribution in the heart and liver, whereas hyperbaric oxygen exposure did not benefit and even impaired the pharmacokinetics and distribution. Particularly, both hypobaric hypoxia and hyperbaric oxygen exposure could not improve the distribution in subcutaneous tumor. Thus, we constructed orthotopic liver tumor model and discussed whether high distribution of the liposomal nanomedicine in the liver, facilitated by hypobaric hypoxia exposure, could ensure their effective accumulation in liver tumor for enhanced cancer therapy. The liposomal nanomedicine with adjuvant hypobaric hypoxia exposure significantly inhibited the growth of orthotopic liver tumor for prolonged survival time, achieved by hypobaric hypoxia-promoted accumulation at tumor sites of the liver. It might be the first example of the application of adjuvant intermittent hypobaric hypoxia exposure in treating liver cancer.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"17 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The addition of the cyclin dependent kinase inhibitor (CDKi) dinaciclib to Poly-(ADP-ribose) polymerase inhibitor (PARPi) therapy is a strategy to overcome resistance to PARPi in tumors that exhibit homologous recombination (HR) deficiencies as well as to expand PARPi therapy to tumors that do not exhibit HR deficiencies. However, combination therapy using pathway inhibitors has been plagued by an inability to administer doses sufficient to achieve clinical benefit due to synergistic toxicities. Here we sought to combine nanoformulations of the PARPi talazoparib, nTLZ, and the CDKi dinaciclib, nDCB, in a nano-cocktail to enhance therapeutic efficacy while maintaining lower doses. Pharmacokinetics of nDCB were assessed to ensure it is compatible with nTLZ. nDCB was combined with nTLZ to generate a nano-cocktail nDCB:nTLZ, which elicits greater cell death in vitro compared to the combination of the free drugs. MDA-MB-231-LUC-D3H2LN xenografts were utilized to assess therapeutic efficacy of the nano-cocktail in terms of tumor progression. Administration of the nano-cocktail significantly slowed tumor progression in the HR proficient animal model compared to administration of free talazoparib and free dinaciclib at the same doses. Histology of the liver, spleen, and kidneys revealed long-term treatment did not induce nanoparticle associated morphological changes. Complete blood count did not reveal any significant hematologic changes after treatment with either the free combination or nano-cocktail. The efficacy and toxicity data suggest that further dose escalation can be pursued in order to achieve a stronger response. These data suggest the administration of combination therapy through the nano-cocktail leads to a better response than the use of free compounds and is a promising strategy for implementing combination therapy in the clinic.
{"title":"A nano-cocktail of the PARP inhibitor talazoparib and CDK inhibitor dinaciclib for the treatment of triple negative breast cancer","authors":"Paige Baldwin, Shicheng Yang, Adrienne Orriols, Sherrie Wang, Needa Brown, Srinivas Sridhar","doi":"10.1186/s12645-023-00240-4","DOIUrl":"https://doi.org/10.1186/s12645-023-00240-4","url":null,"abstract":"The addition of the cyclin dependent kinase inhibitor (CDKi) dinaciclib to Poly-(ADP-ribose) polymerase inhibitor (PARPi) therapy is a strategy to overcome resistance to PARPi in tumors that exhibit homologous recombination (HR) deficiencies as well as to expand PARPi therapy to tumors that do not exhibit HR deficiencies. However, combination therapy using pathway inhibitors has been plagued by an inability to administer doses sufficient to achieve clinical benefit due to synergistic toxicities. Here we sought to combine nanoformulations of the PARPi talazoparib, nTLZ, and the CDKi dinaciclib, nDCB, in a nano-cocktail to enhance therapeutic efficacy while maintaining lower doses. Pharmacokinetics of nDCB were assessed to ensure it is compatible with nTLZ. nDCB was combined with nTLZ to generate a nano-cocktail nDCB:nTLZ, which elicits greater cell death in vitro compared to the combination of the free drugs. MDA-MB-231-LUC-D3H2LN xenografts were utilized to assess therapeutic efficacy of the nano-cocktail in terms of tumor progression. Administration of the nano-cocktail significantly slowed tumor progression in the HR proficient animal model compared to administration of free talazoparib and free dinaciclib at the same doses. Histology of the liver, spleen, and kidneys revealed long-term treatment did not induce nanoparticle associated morphological changes. Complete blood count did not reveal any significant hematologic changes after treatment with either the free combination or nano-cocktail. The efficacy and toxicity data suggest that further dose escalation can be pursued in order to achieve a stronger response. These data suggest the administration of combination therapy through the nano-cocktail leads to a better response than the use of free compounds and is a promising strategy for implementing combination therapy in the clinic.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"102 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140199659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-22DOI: 10.1186/s12645-024-00256-4
Daniela Ferreira, Alexandra R. Fernandes, Pedro V. Baptista
The delivery of therapeutic nucleic acids, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASO) into cells, is widely used in gene therapy. Gold nanoparticles (AuNPs) have proved to be effective in delivering silencing moieties with high efficacy. Moreover, AuNPs offer the possibility of spatial–temporal triggering of cell uptake through light irradiation due to their unique optical properties. Our study focuses on the use of AuNPs as improved vectorisation agents through mild photothermy triggered by visible light irradiation. This method promotes the transfection of oligonucleotides for gene silencing in 2D cells and more complex 3D spheroids. Improving gene silencing strategies in 3D cell cultures is crucial since it provides more effective in vitro models to study cellular responses that closely resemble the in vivo tumour microenvironment. We demonstrate the potential of mild photothermy by effectively silencing the GFP gene in 2D cell cultures: HCT116 and MCF-7. Then we showed that mild photothermy could be effectively used for silencing the c-MYC oncogene transcript, which is greatly overexpressed in cancer cells. A decrease of 25% and 30% in c-MYC expression was observed in HCT116 2D cells and 7-day 3D spheroids, respectively. In summary, our findings offer a novel transfection approach for gene therapy applications in 2D and 3D tumour models. This approach is based on the use of mild photothermy mediated by AuNPs combined with visible laser irradiation that might pave the way for the spatial–temporal control of gene modulation.
{"title":"Mild hyperthermia via gold nanoparticles and visible light irradiation for enhanced siRNA and ASO delivery in 2D and 3D tumour spheroids","authors":"Daniela Ferreira, Alexandra R. Fernandes, Pedro V. Baptista","doi":"10.1186/s12645-024-00256-4","DOIUrl":"https://doi.org/10.1186/s12645-024-00256-4","url":null,"abstract":"The delivery of therapeutic nucleic acids, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASO) into cells, is widely used in gene therapy. Gold nanoparticles (AuNPs) have proved to be effective in delivering silencing moieties with high efficacy. Moreover, AuNPs offer the possibility of spatial–temporal triggering of cell uptake through light irradiation due to their unique optical properties. Our study focuses on the use of AuNPs as improved vectorisation agents through mild photothermy triggered by visible light irradiation. This method promotes the transfection of oligonucleotides for gene silencing in 2D cells and more complex 3D spheroids. Improving gene silencing strategies in 3D cell cultures is crucial since it provides more effective in vitro models to study cellular responses that closely resemble the in vivo tumour microenvironment. We demonstrate the potential of mild photothermy by effectively silencing the GFP gene in 2D cell cultures: HCT116 and MCF-7. Then we showed that mild photothermy could be effectively used for silencing the c-MYC oncogene transcript, which is greatly overexpressed in cancer cells. A decrease of 25% and 30% in c-MYC expression was observed in HCT116 2D cells and 7-day 3D spheroids, respectively. In summary, our findings offer a novel transfection approach for gene therapy applications in 2D and 3D tumour models. This approach is based on the use of mild photothermy mediated by AuNPs combined with visible laser irradiation that might pave the way for the spatial–temporal control of gene modulation.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"1 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140199337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-16DOI: 10.1186/s12645-024-00254-6
Anand Kumar Veeramachineni, Thenapakiam Sathasivam, Ragul Paramasivam, Saravanan Muniyandy, Shafii Bin Khamis, Yau Yan Lim, Janarthanan Pushpamalar
There is a continuous growth of interest in the development of nano-drug delivery systems that could combine therapy and diagnosis of cancer. Novel multifunctional superparamagnetic iron oxide nanoparticles (SPIONs, chemically Fe3O4) conjugated with carboxymethyl sagocellulose (CMSC), and 5-fluorouracil (Fe3O4-CMSC-5FU) were synthesized. The conjugated nanoparticles have the magnetic properties of the SPIONs, which allows the nanoparticles to be localized at the target area by applying an external magnetic field. SPIONs generate heat upon exposure to laser lights, resulting in a photothermic effect. The drug-loading efficiency of 5-FU into the SPIONs-CMSC conjugated nanoparticles was 70 to 84% w/w which could release the drug at intracellular pH (5.4) of cancer cells and resist drug release at pH 7.2. In vivo studies using mice models confirmed the nanoparticles could efficiently deliver 5-FU only to the cancer cells and the anticancer effect was enhanced by laser-induced hyperthermia. The combination of targeted delivery of 5-FU with photothermal therapy (PTT) looks promising for selective killing of cancer cells. Furthermore, SPIONs are an excellent contrasting agent for use in computerized tomography (CT) imaging for determining the tumor location and monitoring the progress of the therapy. The focus of this work was the oncological application of multifunctional Fe3O4-CMSC-5FU nanoparticle conjugates, with an emphasis on therapeutic, diagnostic and prognostic purposes.
{"title":"Carboxymethyl-sagocellulose-stabilized Fe3O4 nanoparticles with 5-fluorouracil as photothermal agents for tumor ablation","authors":"Anand Kumar Veeramachineni, Thenapakiam Sathasivam, Ragul Paramasivam, Saravanan Muniyandy, Shafii Bin Khamis, Yau Yan Lim, Janarthanan Pushpamalar","doi":"10.1186/s12645-024-00254-6","DOIUrl":"https://doi.org/10.1186/s12645-024-00254-6","url":null,"abstract":"There is a continuous growth of interest in the development of nano-drug delivery systems that could combine therapy and diagnosis of cancer. Novel multifunctional superparamagnetic iron oxide nanoparticles (SPIONs, chemically Fe3O4) conjugated with carboxymethyl sagocellulose (CMSC), and 5-fluorouracil (Fe3O4-CMSC-5FU) were synthesized. The conjugated nanoparticles have the magnetic properties of the SPIONs, which allows the nanoparticles to be localized at the target area by applying an external magnetic field. SPIONs generate heat upon exposure to laser lights, resulting in a photothermic effect. The drug-loading efficiency of 5-FU into the SPIONs-CMSC conjugated nanoparticles was 70 to 84% w/w which could release the drug at intracellular pH (5.4) of cancer cells and resist drug release at pH 7.2. In vivo studies using mice models confirmed the nanoparticles could efficiently deliver 5-FU only to the cancer cells and the anticancer effect was enhanced by laser-induced hyperthermia. The combination of targeted delivery of 5-FU with photothermal therapy (PTT) looks promising for selective killing of cancer cells. Furthermore, SPIONs are an excellent contrasting agent for use in computerized tomography (CT) imaging for determining the tumor location and monitoring the progress of the therapy. The focus of this work was the oncological application of multifunctional Fe3O4-CMSC-5FU nanoparticle conjugates, with an emphasis on therapeutic, diagnostic and prognostic purposes.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"7 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140151690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-09DOI: 10.1186/s12645-024-00255-5
Amna H. Faid, M. Abdel Rafea, Sara Gad, Marwa Sharaky, Marwa A. Ramadan
It is crucial to enhance new compounds for the treatment of most malignancies, and graphene oxide/silver nanocomposite (GO/Ag NC) has been paying attention to biomedical applications such as malignancies. In this work, green synthesized Ag@Cht NPs were successfully produced using chitosan for reduction and stabilization and added on GO sheet forming novel GO/Ag NC. Then, the produced anticancer nanomaterials GO, Ag@Cht NPs, and GO/Ag NC were assessed for their cytotoxicity against four distinct cancer cell lines: H460, HCT116, MDA-MB-468, and FaDu cells, at varying concentrations, using SRP assay after 48 h. The prepared nanomaterials were characterized by TEM, UV–Vis spectrophotometry, FTIRs, Raman spectroscopy and XRD. TEM images showed a regular spread of Ag@Cht NPs on the GO sheets with an average particle size of 15 nm. UV–Vis spectrophotometry shows two main characteristic peaks for GO/Ag NC, one close to 230 nm corresponds to GO, while the other peak at 425 nm due to Ag@Cht decorating the GO surface was blue shifted by few nanometers from 427 nm for Ag@Cht. Results of the laser irradiation by DPSS (diode-pumped solid state) confirm the photothermal stability of the prepared nanocomposite as there is no change in surface plasmon resonance (SPR) with varying exposure time. FTIRs measurements indicate that Ag ions interact with a hydroxyl group. This interaction shifts the O–H wavenumber and decreases the bond stretching intensity. In addition, Ag@Cht NPs and Ag/GO NC showed enhanced activity against cancerous cells. Results showed that GO, Ag@Cht NPs, and GO/Ag NC at (200, 400, and 600 µg/ml) had an impact on all evaluated cell lines. In MDA-MB-468, HCT116, H460, and FaDu cells, Ag@Cht NPs had the most effect across all employed cell lines, with IC50 values of 5.5, 9, 6, and 7.75 µg/ml, respectively. In conclusion, the produced novel nanocomposite may be an effective way to treat different cell lines, and future work is to use the prepared nanomaterials as anticancer drug delivery in photothermal chemotherapy combination treatment.
{"title":"Antitumor efficiency and photostability of newly green synthesized silver/graphene oxide nanocomposite on different cancer cell lines","authors":"Amna H. Faid, M. Abdel Rafea, Sara Gad, Marwa Sharaky, Marwa A. Ramadan","doi":"10.1186/s12645-024-00255-5","DOIUrl":"https://doi.org/10.1186/s12645-024-00255-5","url":null,"abstract":"It is crucial to enhance new compounds for the treatment of most malignancies, and graphene oxide/silver nanocomposite (GO/Ag NC) has been paying attention to biomedical applications such as malignancies. In this work, green synthesized Ag@Cht NPs were successfully produced using chitosan for reduction and stabilization and added on GO sheet forming novel GO/Ag NC. Then, the produced anticancer nanomaterials GO, Ag@Cht NPs, and GO/Ag NC were assessed for their cytotoxicity against four distinct cancer cell lines: H460, HCT116, MDA-MB-468, and FaDu cells, at varying concentrations, using SRP assay after 48 h. The prepared nanomaterials were characterized by TEM, UV–Vis spectrophotometry, FTIRs, Raman spectroscopy and XRD. TEM images showed a regular spread of Ag@Cht NPs on the GO sheets with an average particle size of 15 nm. UV–Vis spectrophotometry shows two main characteristic peaks for GO/Ag NC, one close to 230 nm corresponds to GO, while the other peak at 425 nm due to Ag@Cht decorating the GO surface was blue shifted by few nanometers from 427 nm for Ag@Cht. Results of the laser irradiation by DPSS (diode-pumped solid state) confirm the photothermal stability of the prepared nanocomposite as there is no change in surface plasmon resonance (SPR) with varying exposure time. FTIRs measurements indicate that Ag ions interact with a hydroxyl group. This interaction shifts the O–H wavenumber and decreases the bond stretching intensity. In addition, Ag@Cht NPs and Ag/GO NC showed enhanced activity against cancerous cells. Results showed that GO, Ag@Cht NPs, and GO/Ag NC at (200, 400, and 600 µg/ml) had an impact on all evaluated cell lines. In MDA-MB-468, HCT116, H460, and FaDu cells, Ag@Cht NPs had the most effect across all employed cell lines, with IC50 values of 5.5, 9, 6, and 7.75 µg/ml, respectively. In conclusion, the produced novel nanocomposite may be an effective way to treat different cell lines, and future work is to use the prepared nanomaterials as anticancer drug delivery in photothermal chemotherapy combination treatment.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"26 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-26DOI: 10.1186/s12645-024-00249-3
Jamal Moideen Muthu Mohamed, Fazil Ahmad, Mohamed El-Sherbiny, Mohammed Ahmad Al Mohaini, Krishnaraju Venkatesan, Yahya Bin Abdullah Alrashdi, Mamdouh Basheir Eldesoqui, Adel Ehab Ibrahim, Amal Fahmy Dawood, Ateya Megahed Ibrahim, Sami El Deeb
Colorectal cancer (CRC) is a type of cancer that affects the colon or rectum and occurs in individuals over the age of 50, although it can affect people of all ages. Quercetin is a flavonoid, which is a type of plant pigment with antioxidant and anti-inflammatory properties. Some studies have explored the potential of quercetin as an adjuvant therapy to enhance the effectiveness of chemotherapy or radiation therapy. In the proposed work, the nano-biomaterials of solid lipids such as stearic acid (SA) and tripalmitin (TpN) as well as the surfactants tween 80 and span 80 were used to prepare novel quercetin (QuR)-loaded-solid lipid nanoparticles (QuR-SLNs) for medical applications in colorectal cancer (CRC). The resulting bio-nano SLNs’ mean entrapment efficiency (EE) and particle size (PS) were optimized by Box–Behnken design (BBD) approach based on the response-like surface methodology (RSM). The variables include lipid ratio (X1), surfactant ratio (X2), QuR-to-lipid ratio (X3), the sonication time (X4), and the homogenization time (X5). Requirements on the maximum EE (%) and minimum PS (nm) were optimized for the preparation of QuR-SLN. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM) were then used to analyze the optimized SLN and to find the crystalline state of QuR with lipid relationship. In addition, on the Caco-2 cells, at IC50 (49 µM/mL), in vitro cytotoxicity was attained. The optimized QuR-SLN had practically spherical shapes, with % EE and a PS of 97.8 ± 1.16% and 132.16 ± 4.1 nm, respectively. In aqueous media, the degree of lipid crystallinity and the lipid modification was investigated, and the QuR incorporation and release patterns showed high correlations with both. The results showed that over 41.12 ± 1.6% of the bio-nano QuR-SLNs was released gradually over the course of 48 h, demonstrating effective QuR delayed release. Results on apoptotic observations indicate that apoptosis accounts for the majority of cell death, while necrosis, a type of cell death, constitutes a very minor portion. In conclusion, the prepared bio-nano QuR-SLNs might improve cytotoxicity and can act as an ideal carrier for the delivery of QuR and this preparation is used in the treatment of CRC.
{"title":"Optimization and characterization of quercetin-loaded solid lipid nanoparticles for biomedical application in colorectal cancer","authors":"Jamal Moideen Muthu Mohamed, Fazil Ahmad, Mohamed El-Sherbiny, Mohammed Ahmad Al Mohaini, Krishnaraju Venkatesan, Yahya Bin Abdullah Alrashdi, Mamdouh Basheir Eldesoqui, Adel Ehab Ibrahim, Amal Fahmy Dawood, Ateya Megahed Ibrahim, Sami El Deeb","doi":"10.1186/s12645-024-00249-3","DOIUrl":"https://doi.org/10.1186/s12645-024-00249-3","url":null,"abstract":"Colorectal cancer (CRC) is a type of cancer that affects the colon or rectum and occurs in individuals over the age of 50, although it can affect people of all ages. Quercetin is a flavonoid, which is a type of plant pigment with antioxidant and anti-inflammatory properties. Some studies have explored the potential of quercetin as an adjuvant therapy to enhance the effectiveness of chemotherapy or radiation therapy. In the proposed work, the nano-biomaterials of solid lipids such as stearic acid (SA) and tripalmitin (TpN) as well as the surfactants tween 80 and span 80 were used to prepare novel quercetin (QuR)-loaded-solid lipid nanoparticles (QuR-SLNs) for medical applications in colorectal cancer (CRC). The resulting bio-nano SLNs’ mean entrapment efficiency (EE) and particle size (PS) were optimized by Box–Behnken design (BBD) approach based on the response-like surface methodology (RSM). The variables include lipid ratio (X1), surfactant ratio (X2), QuR-to-lipid ratio (X3), the sonication time (X4), and the homogenization time (X5). Requirements on the maximum EE (%) and minimum PS (nm) were optimized for the preparation of QuR-SLN. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM) were then used to analyze the optimized SLN and to find the crystalline state of QuR with lipid relationship. In addition, on the Caco-2 cells, at IC50 (49 µM/mL), in vitro cytotoxicity was attained. The optimized QuR-SLN had practically spherical shapes, with % EE and a PS of 97.8 ± 1.16% and 132.16 ± 4.1 nm, respectively. In aqueous media, the degree of lipid crystallinity and the lipid modification was investigated, and the QuR incorporation and release patterns showed high correlations with both. The results showed that over 41.12 ± 1.6% of the bio-nano QuR-SLNs was released gradually over the course of 48 h, demonstrating effective QuR delayed release. Results on apoptotic observations indicate that apoptosis accounts for the majority of cell death, while necrosis, a type of cell death, constitutes a very minor portion. In conclusion, the prepared bio-nano QuR-SLNs might improve cytotoxicity and can act as an ideal carrier for the delivery of QuR and this preparation is used in the treatment of CRC.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"24 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-22DOI: 10.1186/s12645-024-00253-7
Shengjie Ye, Xier Pan, Linghui Zou, Shuting Ni, Lei Zhang, Yanlong Hong, Kaili Hu
Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and recurrence rate. The efficacy of the first-line drug sorafenib is impeded by drug resistance, which is closely related to activated hepatic stellate cells (HSCs). The natural product luteolin is good at alleviating the activation of HSC. However, its clinical application is limited to poor solubility, bioavailability and lacking of HSCs targeting effects. This study aims to construct luteolin-loaded biomimetic nanoparticles based on HepG2 exosomes for targeting HSCs and enhancing the therapeutic effects of sorafenib on HCC. The HepG2 exosomes extracted were identified by size distribution, Zeta potential and characteristic proteins. Luteolin-loaded polylactic acid-glycolic acid (PLGA) nanoparticles (Lut-NPs) were prepared and wrapped by HepG2 exosomes to form biomimetic nanoparticles (Exo-Lut-NPs). A HepG2 cell sorafenib-resistant model induced by LX2 cell conditioned medium (CM) was established to evaluate the effects of Exo-Lut-NPs on reversing sorafenib-resistant in vitro. And the combined therapeutic effects of Exo-Lut-NPs with sorafenib were evaluated on a HepG2/LX2 subcutaneous xenograft tumor model in vivo. The particle size, drug loading capacity and encapsulation efficiency of Exo-Lut-NPs were 165 ± 10 nm, 2.6 ± 0.2% and 56.9 ± 4.3%, respectively. The in vitro HepG2 sorafenib-resistant model was induced by the CM of LX2 cells, and the results showed that Exo-Lut-NPs partially reversed the sorafenib resistance of HepG2 cells by affecting the CM of LX2 cells. The combined therapy of Exo-Lut-NPs with sorafenib markedly suppressed tumor growth in a HepG2/LX2 subcutaneous xenograft tumor model. This study suggests that the Exo-Lut-NP is a novel and promising biomimetic delivery system which can combine with sorafenib for HCC therapy.
{"title":"HepG2 exosomes coated luteolin nanoparticles remodeling hepatic stellate cells and combination with sorafenib for the treatment of hepatocellular carcinoma","authors":"Shengjie Ye, Xier Pan, Linghui Zou, Shuting Ni, Lei Zhang, Yanlong Hong, Kaili Hu","doi":"10.1186/s12645-024-00253-7","DOIUrl":"https://doi.org/10.1186/s12645-024-00253-7","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and recurrence rate. The efficacy of the first-line drug sorafenib is impeded by drug resistance, which is closely related to activated hepatic stellate cells (HSCs). The natural product luteolin is good at alleviating the activation of HSC. However, its clinical application is limited to poor solubility, bioavailability and lacking of HSCs targeting effects. This study aims to construct luteolin-loaded biomimetic nanoparticles based on HepG2 exosomes for targeting HSCs and enhancing the therapeutic effects of sorafenib on HCC. The HepG2 exosomes extracted were identified by size distribution, Zeta potential and characteristic proteins. Luteolin-loaded polylactic acid-glycolic acid (PLGA) nanoparticles (Lut-NPs) were prepared and wrapped by HepG2 exosomes to form biomimetic nanoparticles (Exo-Lut-NPs). A HepG2 cell sorafenib-resistant model induced by LX2 cell conditioned medium (CM) was established to evaluate the effects of Exo-Lut-NPs on reversing sorafenib-resistant in vitro. And the combined therapeutic effects of Exo-Lut-NPs with sorafenib were evaluated on a HepG2/LX2 subcutaneous xenograft tumor model in vivo. The particle size, drug loading capacity and encapsulation efficiency of Exo-Lut-NPs were 165 ± 10 nm, 2.6 ± 0.2% and 56.9 ± 4.3%, respectively. The in vitro HepG2 sorafenib-resistant model was induced by the CM of LX2 cells, and the results showed that Exo-Lut-NPs partially reversed the sorafenib resistance of HepG2 cells by affecting the CM of LX2 cells. The combined therapy of Exo-Lut-NPs with sorafenib markedly suppressed tumor growth in a HepG2/LX2 subcutaneous xenograft tumor model. This study suggests that the Exo-Lut-NP is a novel and promising biomimetic delivery system which can combine with sorafenib for HCC therapy.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"63 2 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139920882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The medical field is faced with the difficult task of developing a new approach to curing cancer, which is prevalent in organs such as the breast and ovaries and has a high mortality rate. Since chemotherapy is the conventional method of treatment, efforts are being made to improve it to help patients function better. Fortunately, with the use of nanocarriers and their remarkable ability to manage and direct drug delivery, progress is being made in cancer treatment. In addition, folic acid-coated nanocarriers offer several advantages in drug delivery, including improved stability, bioavailability, targeted delivery and drug solubility. These properties make them promising tools for improving cancer treatment efficacy. This research focused on investigating the stability of a specific niosomal formulation (consisting of Span 60 and cholesterol) under different temperature conditions (4 and 25 ℃) for 2 months. In addition, the drug release rate of the formulation was evaluated. The results showed that the size and polydispersity index increased significantly in the stability studies, but the entrapment efficiency% decreased dramatically over time. In addition, encapsulation of drugs in niosomal formulations resulted in stable and slow drug release. The cytotoxicity evaluation results of formulations containing doxorubicin and cisplatin show their significant inhibitory effect on both breast and ovarian cancer cell lines (IC50 for DOX–CIS–Nio@PEG–FA formulation was 6.11 and 17.87 µg/mL for A2780 and MCF-7, respectively). Niosomes loaded with a combination of two drugs were found to affect gene expression in the cancer cell lines tested. They decreased the expression of BCl2, VEGF, CCND1, and HER2 genes while increasing the expression of BAX gene. Flow cytometry results indicated that niosomes loaded with doxorubicin and cisplatin increased the rate of apoptosis in both cell lines compared to a drug mixture. ROS and cell cycle arrest, confirm the significant inhibition of cancer cells and their destruction in the presence of the synthesized noisome formulation in comparison to free drugs and the combination of two drugs. The potential of this novel approach for delivering drugs to cancer cells lies in the ability to combine treatments and target multiple cancers simultaneously. Such formulations allow co-delivery of drugs to different cancer cells, thereby improving the efficacy of chemotherapy through synergistic effects between drugs.
{"title":"Folic acid-functionalized PEGylated niosomes co-encapsulated cisplatin and doxoribicin exhibit enhanced anticancer efficacy","authors":"Mona Safari Sharafshadeh, Farzaneh Tafvizi, Parvin Khodarahmi, Somayeh Ehtesham","doi":"10.1186/s12645-024-00252-8","DOIUrl":"https://doi.org/10.1186/s12645-024-00252-8","url":null,"abstract":"The medical field is faced with the difficult task of developing a new approach to curing cancer, which is prevalent in organs such as the breast and ovaries and has a high mortality rate. Since chemotherapy is the conventional method of treatment, efforts are being made to improve it to help patients function better. Fortunately, with the use of nanocarriers and their remarkable ability to manage and direct drug delivery, progress is being made in cancer treatment. In addition, folic acid-coated nanocarriers offer several advantages in drug delivery, including improved stability, bioavailability, targeted delivery and drug solubility. These properties make them promising tools for improving cancer treatment efficacy. This research focused on investigating the stability of a specific niosomal formulation (consisting of Span 60 and cholesterol) under different temperature conditions (4 and 25 ℃) for 2 months. In addition, the drug release rate of the formulation was evaluated. The results showed that the size and polydispersity index increased significantly in the stability studies, but the entrapment efficiency% decreased dramatically over time. In addition, encapsulation of drugs in niosomal formulations resulted in stable and slow drug release. The cytotoxicity evaluation results of formulations containing doxorubicin and cisplatin show their significant inhibitory effect on both breast and ovarian cancer cell lines (IC50 for DOX–CIS–Nio@PEG–FA formulation was 6.11 and 17.87 µg/mL for A2780 and MCF-7, respectively). Niosomes loaded with a combination of two drugs were found to affect gene expression in the cancer cell lines tested. They decreased the expression of BCl2, VEGF, CCND1, and HER2 genes while increasing the expression of BAX gene. Flow cytometry results indicated that niosomes loaded with doxorubicin and cisplatin increased the rate of apoptosis in both cell lines compared to a drug mixture. ROS and cell cycle arrest, confirm the significant inhibition of cancer cells and their destruction in the presence of the synthesized noisome formulation in comparison to free drugs and the combination of two drugs. The potential of this novel approach for delivering drugs to cancer cells lies in the ability to combine treatments and target multiple cancers simultaneously. Such formulations allow co-delivery of drugs to different cancer cells, thereby improving the efficacy of chemotherapy through synergistic effects between drugs. ","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"94 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-08DOI: 10.1186/s12645-024-00248-4
Haiwei Xiong, Xiaoyan Nie, Wei Cao, Jia Zhu, Jian Chen, Ruihao Liu, Yingliang Li
Nowadays, silver nanoparticles (AgNPs) have attracted the attention of many researchers due to their special physical, chemical, and biological properties. There is strong evidence that biogenic AgNPs can act as potent anticancer agents through the production of reactive oxygen species (ROS) and initiate the mitochondrial pathway of apoptosis. That is why we decided to use Nepeta bracteata Benth flower extract for the first time to bio-synthesize AgNPs and study their cytotoxic and apoptotic effects on SK-BR-3 cells. AgNPs were biosynthesized at 70 °C after mixing silver nitrate and flower extract with a specific ratio and concentration, then were characterized using various analytical techniques, such as FESEM, FTIR, EDS, and zeta potential. Studies have shown that AgNPs have an irregular and circular shape, with about 99% by weight of silver, carbon, and oxygen. On the other hand, the appropriate size (below 57 nm) and surface charge (− 11.52 mV) make them stable in biological fluids. The better cytotoxic effect of AgNPs compared to flower extract on SK-BR-3 cells was investigated using the MTT method. The positive effect of AgNPs on inhibiting the growth of SK-BR-3 breast cancer cells was again confirmed by the sulforhodamine B staining method, so that AgNPs were able to decrease the density of cancer cells in a concentration-dependent manner. In addition, the flow cytometry test proved that biosynthesized AgNPs using Nepeta bracteata Benth flower extract can induce apoptosis in SK-BR-3 cancer cells. Real-time PCR then proved that the ratio of Bak1/Bclx, as well as caspase-3 expression, was increased due to active ROS-producing biomolecules present in the plant extract, and therefore, AgNPs can activate the mitochondria-dependent apoptosis pathway in breast cancer cells. Finally, their negligible oxidative stress on erythrocytes was confirmed by the lipid peroxidation method and showed that biosynthesized AgNPs can be used for breast cancer treatment without showing adverse effects on erythrocytes.
{"title":"Investigation of mitochondria-dependent apoptosis pathway and lipid peroxidation level induced by biosynthesized silver nanoparticles: caspase-3 activation, BAK1/BCLx regulation and malondialdehyde production","authors":"Haiwei Xiong, Xiaoyan Nie, Wei Cao, Jia Zhu, Jian Chen, Ruihao Liu, Yingliang Li","doi":"10.1186/s12645-024-00248-4","DOIUrl":"https://doi.org/10.1186/s12645-024-00248-4","url":null,"abstract":"Nowadays, silver nanoparticles (AgNPs) have attracted the attention of many researchers due to their special physical, chemical, and biological properties. There is strong evidence that biogenic AgNPs can act as potent anticancer agents through the production of reactive oxygen species (ROS) and initiate the mitochondrial pathway of apoptosis. That is why we decided to use Nepeta bracteata Benth flower extract for the first time to bio-synthesize AgNPs and study their cytotoxic and apoptotic effects on SK-BR-3 cells. AgNPs were biosynthesized at 70 °C after mixing silver nitrate and flower extract with a specific ratio and concentration, then were characterized using various analytical techniques, such as FESEM, FTIR, EDS, and zeta potential. Studies have shown that AgNPs have an irregular and circular shape, with about 99% by weight of silver, carbon, and oxygen. On the other hand, the appropriate size (below 57 nm) and surface charge (− 11.52 mV) make them stable in biological fluids. The better cytotoxic effect of AgNPs compared to flower extract on SK-BR-3 cells was investigated using the MTT method. The positive effect of AgNPs on inhibiting the growth of SK-BR-3 breast cancer cells was again confirmed by the sulforhodamine B staining method, so that AgNPs were able to decrease the density of cancer cells in a concentration-dependent manner. In addition, the flow cytometry test proved that biosynthesized AgNPs using Nepeta bracteata Benth flower extract can induce apoptosis in SK-BR-3 cancer cells. Real-time PCR then proved that the ratio of Bak1/Bclx, as well as caspase-3 expression, was increased due to active ROS-producing biomolecules present in the plant extract, and therefore, AgNPs can activate the mitochondria-dependent apoptosis pathway in breast cancer cells. Finally, their negligible oxidative stress on erythrocytes was confirmed by the lipid peroxidation method and showed that biosynthesized AgNPs can be used for breast cancer treatment without showing adverse effects on erythrocytes.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"18 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-07DOI: 10.1186/s12645-024-00251-9
Liting Sun, Cong Meng, Zhongtao Zhang, Yao Luo, Zhengyang Yang, Hongwei Yao
The morbidity and mortality of gastrointestinal tumours remain high worldwide. Surgical resection is currently the most critical radical therapeutic schedule, while postoperative complications and sentinel lymph node (SLN) identification are closely related to the outcome. Indocyanine green (ICG)-mediated fluorescence imaging is increasingly being used in gastrointestinal surgery. It has been embraced by various surgical disciplines as a potential method to improve lymph node detection and enhance surgical field visualization. ICG can passively concentrate in SLN because of enhanced permeation and retention effects. After excitation by near-infrared light devices, SLN can display higher intensity fluorescence, helping visualization for better lymph node dissection. In addition, visual assessment of intestinal blood flow through ICG may reduce the incidence of anastomotic leakage. Although it has good clinical application, ICG-imaging still faces some problems, such as a higher false-negative rate, poorly targeted biodistribution, and lower fluorescence contrast, due to the lack of active tumour targeting. Thus, different ICG-coupled nanoparticles with inherent characteristics or functional modification-enhanced SLN identification features for gastrointestinal cancers bring benefit through active tumour targeting, superior tumour-background ratio, and high resolution. Nano-ICG combined with potential substances, including enhanced imaging contrast and/or combination therapy (chemotherapy, targeted therapy, immunotherapy, etc.), have been packaged and accumulated in the tumour area through active targeting for multimodal imaging and treatment. In this review, we outline the intraoperative application and possible future nanodirections of ICG in gastrointestinal cancer. The prospects and challenges of nano-ICG diagnostic and therapeutic methods in clinical applications are also discussed.
{"title":"Opportunities and challenges of indocyanine green in gastrointestinal cancers for intraoperative and nano-medicine application","authors":"Liting Sun, Cong Meng, Zhongtao Zhang, Yao Luo, Zhengyang Yang, Hongwei Yao","doi":"10.1186/s12645-024-00251-9","DOIUrl":"https://doi.org/10.1186/s12645-024-00251-9","url":null,"abstract":"The morbidity and mortality of gastrointestinal tumours remain high worldwide. Surgical resection is currently the most critical radical therapeutic schedule, while postoperative complications and sentinel lymph node (SLN) identification are closely related to the outcome. Indocyanine green (ICG)-mediated fluorescence imaging is increasingly being used in gastrointestinal surgery. It has been embraced by various surgical disciplines as a potential method to improve lymph node detection and enhance surgical field visualization. ICG can passively concentrate in SLN because of enhanced permeation and retention effects. After excitation by near-infrared light devices, SLN can display higher intensity fluorescence, helping visualization for better lymph node dissection. In addition, visual assessment of intestinal blood flow through ICG may reduce the incidence of anastomotic leakage. Although it has good clinical application, ICG-imaging still faces some problems, such as a higher false-negative rate, poorly targeted biodistribution, and lower fluorescence contrast, due to the lack of active tumour targeting. Thus, different ICG-coupled nanoparticles with inherent characteristics or functional modification-enhanced SLN identification features for gastrointestinal cancers bring benefit through active tumour targeting, superior tumour-background ratio, and high resolution. Nano-ICG combined with potential substances, including enhanced imaging contrast and/or combination therapy (chemotherapy, targeted therapy, immunotherapy, etc.), have been packaged and accumulated in the tumour area through active targeting for multimodal imaging and treatment. In this review, we outline the intraoperative application and possible future nanodirections of ICG in gastrointestinal cancer. The prospects and challenges of nano-ICG diagnostic and therapeutic methods in clinical applications are also discussed. ","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"49 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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