Designing and preparing a co-delivery system based on polymeric micelles have attracted in recent years. Co-delivery of anti-cancer agents within pH-sensitive polymeric micelles could provide superior advantages over the co-administration of free drugs, since it enables simultaneous delivery of drugs to reach an optimum synergistic dose right to the tumor. DOX was conjugated to the polymer through a hydrazine linker by Schiff’s base reaction. Then, DTX was encapsulated into the core of the polymer to the resulting DOX-Hyd-PM/DTX micelle with optimum molar ratios of 1:1 and 1:5 (DOX/DTX). The final formulations showed the desired particle size and increased release of DOX and DTX in acidic media (pH 5.5). The cytotoxicity assay of DOX-Hyd-PM/DTX indicated the highest synergistic effect on both 4T1 and TUBO cell lines over other formulations. Interestingly, in accordance with in vitro results, DOX-Hyd-PM/DTX revealed a promising anti-tumor activity in mice-bearing 4T1 breast cancer tumor with higher tumor accumulation of DOX and DTX after 24 h compared to free drugs combination. These findings point to the potential use of such smart nanodrug delivery systems in cancer treatment, where the synergistic effect of both drugs may be used to enhance therapeutic response.
{"title":"pH-sensitive polymeric micelles enhance the co-delivery of doxorubicin and docetaxel: an emerging modality for treating breast cancer","authors":"Leila Farhoudi, Seyedeh Maryam Hosseinikhah, Amin Kazemi-Beydokhti, Leila Arabi, Seyedeh Hoda Alavizadeh, Seyedeh Alia Moosavian, Mahmoud Reza Jaafari","doi":"10.1186/s12645-024-00275-1","DOIUrl":"https://doi.org/10.1186/s12645-024-00275-1","url":null,"abstract":"Designing and preparing a co-delivery system based on polymeric micelles have attracted in recent years. Co-delivery of anti-cancer agents within pH-sensitive polymeric micelles could provide superior advantages over the co-administration of free drugs, since it enables simultaneous delivery of drugs to reach an optimum synergistic dose right to the tumor. DOX was conjugated to the polymer through a hydrazine linker by Schiff’s base reaction. Then, DTX was encapsulated into the core of the polymer to the resulting DOX-Hyd-PM/DTX micelle with optimum molar ratios of 1:1 and 1:5 (DOX/DTX). The final formulations showed the desired particle size and increased release of DOX and DTX in acidic media (pH 5.5). The cytotoxicity assay of DOX-Hyd-PM/DTX indicated the highest synergistic effect on both 4T1 and TUBO cell lines over other formulations. Interestingly, in accordance with in vitro results, DOX-Hyd-PM/DTX revealed a promising anti-tumor activity in mice-bearing 4T1 breast cancer tumor with higher tumor accumulation of DOX and DTX after 24 h compared to free drugs combination. These findings point to the potential use of such smart nanodrug delivery systems in cancer treatment, where the synergistic effect of both drugs may be used to enhance therapeutic response. ","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"12 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742304","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}
Anlotinib is a targeted therapy indicated for some malignancies, including advanced non-small cell lung cancer (NSCLC). However, noninvasive biomarkers for identifying patients who will benefit from this disease remain lacking. Here, we investigated the potential of small extracellular vesicle (sEV) microRNAs (miRNAs) as predictive biomarkers for anlotinib efficacy. A total of 20 advanced NSCLC patients were enrolled. Patients were classified as having stable disease (SD) or progressive disease (PD) after the initial efficacy assessment. Seven differentially expressed miRNAs (DEMs) were identified. Among them, miR-941 was significantly upregulated in the PD group, while the others were downregulated. Furthermore, these six downregulated miRNAs (miR-30a-3p, miR-150-5p, miR-122-5p, miR-10b-5p, miR-92a-3p, and miR-150-3p) were more pronounced in nonsmoking patients. It was found that sEV miRNAs have the potential to predict the benefit of anlotinib.
{"title":"Extracellular vesicle miRNAs for predicting the efficacy of late-line treatment with anlotinib in patients with lung adenocarcinoma","authors":"Aimi Huang, Fuchuang Zhang, Jiyang Zhang, Xiaoya Xu, Zhikuan Li, Sheng Chen, Baoning Nian, Dadong Zhang, Baohui Han, Aiqin Gu, Weimin Wang","doi":"10.1186/s12645-024-00273-3","DOIUrl":"https://doi.org/10.1186/s12645-024-00273-3","url":null,"abstract":"Anlotinib is a targeted therapy indicated for some malignancies, including advanced non-small cell lung cancer (NSCLC). However, noninvasive biomarkers for identifying patients who will benefit from this disease remain lacking. Here, we investigated the potential of small extracellular vesicle (sEV) microRNAs (miRNAs) as predictive biomarkers for anlotinib efficacy. A total of 20 advanced NSCLC patients were enrolled. Patients were classified as having stable disease (SD) or progressive disease (PD) after the initial efficacy assessment. Seven differentially expressed miRNAs (DEMs) were identified. Among them, miR-941 was significantly upregulated in the PD group, while the others were downregulated. Furthermore, these six downregulated miRNAs (miR-30a-3p, miR-150-5p, miR-122-5p, miR-10b-5p, miR-92a-3p, and miR-150-3p) were more pronounced in nonsmoking patients. It was found that sEV miRNAs have the potential to predict the benefit of anlotinib.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"49 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510326","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}
Lung cancer has been mentioned as the first and second most prevalent cancer among males and females worldwide, respectively since conventional approaches do not have enough efficiency in its suppression. Therefore, a biocompatible and efficient polylactic-co-glycolic acid (PLGA: P)- poly-ε-caprolactone (PCL: P) copolymer was fabricated for delivery of relatively insoluble curcumin (Cur) to A549 lung cancer cells. Next, the physicochemical aspects of the synthesized nanobeads were characterized by applying analytical sets, including FT-IR, DLS, TEM, and TGA as nano-metric size (20–45 nm) and 1.29% of Cur entrapment efficiency were determined for P-P-Cur nano-beads. Thereafter, a controlled (5% within 2 h at pH 7.4) and pH-sensitive (nearly 50% within 4 h at pH 5.0) drug release manner was observed for P-P-Cur nanobeads. Thereafter, biomedical assays were conducted for the cancer suppression ability of nanobeads. 41% cell viability after 24 h of treatment with 200 nM concentration and 7.55% cell cycle arrest at 5 h of post-treatment with 100 nM (IC50) concentration were attained for P-P-Cur. Also, 7-fold increase and 2-fold decrease in the expressions of Caspase-9 (apoptotic gene) and Bcl2 (anti-apoptotic gene) were observed which have further approved the cancer inhibition potency of the P-P-Cur sample. The cellular uptake results indicated 91% internalization in A549 cells while it was less than 1% for the pure Cur. These data have demonstrated that P-P-Cur can use as a biocompatible drug delivery system for Cur and treatment of lung cancer.
{"title":"Biocompatible PLGA-PCL nanobeads for efficient delivery of curcumin to lung cancer","authors":"Sheida Sadeghi, Javad Mohammadnejad, Akram Eidi, Hanieh Jafary","doi":"10.1186/s12645-024-00272-4","DOIUrl":"https://doi.org/10.1186/s12645-024-00272-4","url":null,"abstract":"Lung cancer has been mentioned as the first and second most prevalent cancer among males and females worldwide, respectively since conventional approaches do not have enough efficiency in its suppression. Therefore, a biocompatible and efficient polylactic-co-glycolic acid (PLGA: P)- poly-ε-caprolactone (PCL: P) copolymer was fabricated for delivery of relatively insoluble curcumin (Cur) to A549 lung cancer cells. Next, the physicochemical aspects of the synthesized nanobeads were characterized by applying analytical sets, including FT-IR, DLS, TEM, and TGA as nano-metric size (20–45 nm) and 1.29% of Cur entrapment efficiency were determined for P-P-Cur nano-beads. Thereafter, a controlled (5% within 2 h at pH 7.4) and pH-sensitive (nearly 50% within 4 h at pH 5.0) drug release manner was observed for P-P-Cur nanobeads. Thereafter, biomedical assays were conducted for the cancer suppression ability of nanobeads. 41% cell viability after 24 h of treatment with 200 nM concentration and 7.55% cell cycle arrest at 5 h of post-treatment with 100 nM (IC50) concentration were attained for P-P-Cur. Also, 7-fold increase and 2-fold decrease in the expressions of Caspase-9 (apoptotic gene) and Bcl2 (anti-apoptotic gene) were observed which have further approved the cancer inhibition potency of the P-P-Cur sample. The cellular uptake results indicated 91% internalization in A549 cells while it was less than 1% for the pure Cur. These data have demonstrated that P-P-Cur can use as a biocompatible drug delivery system for Cur and treatment of lung cancer.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"35 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141530125","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 : 2024-06-04DOI: 10.1186/s12645-024-00266-2
Liu Xu, Ruoyu Wu, Jiajing Ni, Lufei Jin, Kaiwei Xu, Yuchao Zhu, Lu Hong, Chunqu Chen, Linwei Wang, Lubin Zhu, Weijian Zhou, Wenqi Shen, Jianhua Wang
The tumor-specific immune responses, essential for removing residual lesions and preventing tumor metastases, can be stimulated by tumor-associated antigens (TAAs) released following photothermal therapy (PTT). However, due to the immunosuppressed microenvironment of pancreatic ductal adenocarcinoma (PDAC), the TAAs released by PTT are difficult to induce an effective immune response. In this work, we prepared the mesoporous silica (mSiO2) coated black titanium dioxide (bTiO2) photothermal nanoparticles (NPs) for enhanced photothermal-immunotherapy toward PDAC, in which resiquimod (R848) was loaded and DOTA-Gd was conjugated. The NPs are specified as bTiO2@mSiO2@Gd/R848 and abbreviated to NPs/R848. R848 as a kind of Toll-like receptor 7/8 agonist can remodel the tumor microenvironment (TME) in PDAC and induce a strong immune response. Furthermore, DOTA-Gd serves as a magnetic resonance imaging (MRI) contrast agent to improve the T1-weighted MRI performance of the NPs. In vitro results of this study show that NPs/R848 could thermally ablate tumor cells and efficiently trigger dendritic cell (DC) maturation. The results of in vivo investigations demonstrate that the combined use of photothermal-immunotherapy exhibits a significant inhibitory effect on tumor growth. Besides, it promoted maturation of DCs and enhanced infiltration of CD8 + , CD4 + T cells to improve the TME in PDAC. Our study anticipates that by encouraging the maturation of DCs, this strategy will improve the TME and enable the successful photothermal-immunotherapy of PDAC.
光热疗法（PTT）释放的肿瘤相关抗原（TAAs）可刺激肿瘤特异性免疫反应，这对清除残余病灶和防止肿瘤转移至关重要。然而，由于胰腺导管腺癌（PDAC）的免疫抑制微环境，PTT释放的TAA很难诱导有效的免疫反应。在这项研究中，我们制备了介孔二氧化硅（mSiO2）包覆黑色二氧化钛（bTiO2）的光热纳米颗粒（NPs），用于增强对PDAC的光热免疫疗法。NPs的名称为bTiO2@mSiO2@Gd/R848，缩写为NPs/R848。R848是一种Toll样受体7/8激动剂，能重塑PDAC的肿瘤微环境（TME）并诱导强烈的免疫反应。此外，DOTA-Gd 可作为磁共振成像（MRI）造影剂，改善 NPs 的 T1 加权 MRI 性能。本研究的体外研究结果表明，NPs/R848可以热消融肿瘤细胞，并有效地触发树突状细胞（DC）成熟。体内研究结果表明，联合使用光热免疫疗法对肿瘤生长有显著的抑制作用。此外，它还促进了 DC 的成熟，并增强了 CD8 +、CD4 + T 细胞的浸润，从而改善了 PDAC 的 TME。我们的研究预计，通过促进DCs的成熟，这一策略将改善TME，使PDAC的光热免疫疗法获得成功。
{"title":"Black TiO2-based nanoparticles as Toll-like receptor stimulator delivery system for enhanced photothermal-immunotherapy of pancreatic cancer","authors":"Liu Xu, Ruoyu Wu, Jiajing Ni, Lufei Jin, Kaiwei Xu, Yuchao Zhu, Lu Hong, Chunqu Chen, Linwei Wang, Lubin Zhu, Weijian Zhou, Wenqi Shen, Jianhua Wang","doi":"10.1186/s12645-024-00266-2","DOIUrl":"https://doi.org/10.1186/s12645-024-00266-2","url":null,"abstract":"The tumor-specific immune responses, essential for removing residual lesions and preventing tumor metastases, can be stimulated by tumor-associated antigens (TAAs) released following photothermal therapy (PTT). However, due to the immunosuppressed microenvironment of pancreatic ductal adenocarcinoma (PDAC), the TAAs released by PTT are difficult to induce an effective immune response. In this work, we prepared the mesoporous silica (mSiO2) coated black titanium dioxide (bTiO2) photothermal nanoparticles (NPs) for enhanced photothermal-immunotherapy toward PDAC, in which resiquimod (R848) was loaded and DOTA-Gd was conjugated. The NPs are specified as bTiO2@mSiO2@Gd/R848 and abbreviated to NPs/R848. R848 as a kind of Toll-like receptor 7/8 agonist can remodel the tumor microenvironment (TME) in PDAC and induce a strong immune response. Furthermore, DOTA-Gd serves as a magnetic resonance imaging (MRI) contrast agent to improve the T1-weighted MRI performance of the NPs. In vitro results of this study show that NPs/R848 could thermally ablate tumor cells and efficiently trigger dendritic cell (DC) maturation. The results of in vivo investigations demonstrate that the combined use of photothermal-immunotherapy exhibits a significant inhibitory effect on tumor growth. Besides, it promoted maturation of DCs and enhanced infiltration of CD8 + , CD4 + T cells to improve the TME in PDAC. Our study anticipates that by encouraging the maturation of DCs, this strategy will improve the TME and enable the successful photothermal-immunotherapy of PDAC.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"43 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254113","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 objective of this study was to synthesize a novel antibacterial and anticancer nanoformulation using aloe vera-derived carbon quantum dots (Cdot) and chromium-doped alumina nanoparticles (Al2O3:Cr/Cdot NPs) via a sol–gel method. X-ray diffraction (XRD) analysis confirmed crystalline NPs with a size range of 10–12 nm, while energy-dispersive X-ray spectroscopy (EDS) revealed their elemental composition without impurities. Fourier-transform infrared spectroscopy (FT-IR) indicated strong interactions between Cdot and Al2O3:Cr NPs, forming a robust heterostructure. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images provided visual confirmation of monodisperse, spherical NPs, ensuring uniformity for further applications. Evaluation of reactive oxygen species (ROS) demonstrated superior generation of singlet oxygen and hydroxyl radicals by Al2O3:Cr/Cdot NPs, essential for photodynamic therapy. Minimum inhibitory concentration (MIC) tests revealed potent antibacterial activity against drug-resistant bacteria, inhibiting biofilm formation by 89% and 95% for MRSA and P. aeruginosa PAO1, respectively. Furthermore, the anticancer activity of Al2O3:Cr/Cdot NPs was assessed using C26 cells, demonstrating enhanced cytotoxicity upon UVA exposure. The NPs exhibited an inhibitory concentration (IC50) of 20 μg/mL without UVA exposure, decreasing to 10 μg/mL with UVA exposure, highlighting the synergistic effect of UVA light in enhancing cytotoxicity. Overall, these findings underscore the significant potential of Al2O3:Cr/Cdot NPs as multifunctional agents for addressing drug-resistant bacteria and advancing cancer therapy, offering promising avenues for nanomedicine research and development.
{"title":"Development of a novel nanoformulation based on aloe vera-derived carbon quantum dot and chromium-doped alumina nanoparticle (Al2O3:Cr@Cdot NPs): evaluating the anticancer and antimicrobial activities of nanoparticles in photodynamic therapy","authors":"Merat Karimi, Mina Homayoonfal, Mostafa Zahedifar, Amirreza Ostadian, Reyhaneh Adibi, Bahareh Mohammadzadeh, Arash Raisi, Fatemeh Ravaei, Somaye Rashki, Mahsa Khakbraghi, Michael Hamblin, Zahra Kheirkhah, Ehsan Sadeghi, Majid Nejati, Hamed Mirzaei","doi":"10.1186/s12645-024-00260-8","DOIUrl":"https://doi.org/10.1186/s12645-024-00260-8","url":null,"abstract":"The objective of this study was to synthesize a novel antibacterial and anticancer nanoformulation using aloe vera-derived carbon quantum dots (Cdot) and chromium-doped alumina nanoparticles (Al2O3:Cr/Cdot NPs) via a sol–gel method. X-ray diffraction (XRD) analysis confirmed crystalline NPs with a size range of 10–12 nm, while energy-dispersive X-ray spectroscopy (EDS) revealed their elemental composition without impurities. Fourier-transform infrared spectroscopy (FT-IR) indicated strong interactions between Cdot and Al2O3:Cr NPs, forming a robust heterostructure. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images provided visual confirmation of monodisperse, spherical NPs, ensuring uniformity for further applications. Evaluation of reactive oxygen species (ROS) demonstrated superior generation of singlet oxygen and hydroxyl radicals by Al2O3:Cr/Cdot NPs, essential for photodynamic therapy. Minimum inhibitory concentration (MIC) tests revealed potent antibacterial activity against drug-resistant bacteria, inhibiting biofilm formation by 89% and 95% for MRSA and P. aeruginosa PAO1, respectively. Furthermore, the anticancer activity of Al2O3:Cr/Cdot NPs was assessed using C26 cells, demonstrating enhanced cytotoxicity upon UVA exposure. The NPs exhibited an inhibitory concentration (IC50) of 20 μg/mL without UVA exposure, decreasing to 10 μg/mL with UVA exposure, highlighting the synergistic effect of UVA light in enhancing cytotoxicity. Overall, these findings underscore the significant potential of Al2O3:Cr/Cdot NPs as multifunctional agents for addressing drug-resistant bacteria and advancing cancer therapy, offering promising avenues for nanomedicine research and development.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141253673","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 : 2024-05-14DOI: 10.1186/s12645-024-00262-6
Danhuan Zhang, Lingyun Chen, Yang Zhao, Hao Ni, Qiuying Quan, Jun Ma, Lingchuan Guo
The utilization of liposomes in drug delivery has garnered significant attention due to their efficient drug loading capacity and excellent biocompatibility, rendering them a promising platform for tumor therapy. However, the average size of liposomes ~ 100 nm leads to liposomes being susceptible to hepatic and renal metabolism to excretion outside the body leading to poor drug delivery efficiency with a total utilization rate of less than 0.7%, resulting in unfavorable treatment outcomes. We have developed a novel liposome platform equipped with tumor surface nucleolin-targeting capacity to enhance drug accumulation at the tumor in vivo. The encapsulation of doxorubicin through thin film hydration has resulted in the formation of D@L-AS1411. Through in vivo experiments, we have demonstrated the effective accumulation of D@L-AS1411 at the tumor site and its ability to improve doxorubicin utilization rates by 40%. Additionally, D@L-AS1411 induces immunogenic death of tumor cells, release of tumor-associated antigens, upregulation of calreticulin expression, and recruitment of active T cell infiltration, and ultimately improves the therapeutic efficacy against tumors (70%). Based on the nucleic acid aptamer AS1411, D@L-1411 is developed to specifically enhance the accumulation of Dox at tumor sites, thereby inhibiting and enhancing the anti-tumor effect. In summary, this study not only provides an efficient tumor-targeting delivery platform but also contributes to the improvement of chemotherapy–immunotherapy combination for tumor treatment strategy in the clinic.
{"title":"As1411-modified liposomes to enhance drug utilization and augment the anti-tumor efficacy","authors":"Danhuan Zhang, Lingyun Chen, Yang Zhao, Hao Ni, Qiuying Quan, Jun Ma, Lingchuan Guo","doi":"10.1186/s12645-024-00262-6","DOIUrl":"https://doi.org/10.1186/s12645-024-00262-6","url":null,"abstract":"The utilization of liposomes in drug delivery has garnered significant attention due to their efficient drug loading capacity and excellent biocompatibility, rendering them a promising platform for tumor therapy. However, the average size of liposomes ~ 100 nm leads to liposomes being susceptible to hepatic and renal metabolism to excretion outside the body leading to poor drug delivery efficiency with a total utilization rate of less than 0.7%, resulting in unfavorable treatment outcomes. We have developed a novel liposome platform equipped with tumor surface nucleolin-targeting capacity to enhance drug accumulation at the tumor in vivo. The encapsulation of doxorubicin through thin film hydration has resulted in the formation of D@L-AS1411. Through in vivo experiments, we have demonstrated the effective accumulation of D@L-AS1411 at the tumor site and its ability to improve doxorubicin utilization rates by 40%. Additionally, D@L-AS1411 induces immunogenic death of tumor cells, release of tumor-associated antigens, upregulation of calreticulin expression, and recruitment of active T cell infiltration, and ultimately improves the therapeutic efficacy against tumors (70%). Based on the nucleic acid aptamer AS1411, D@L-1411 is developed to specifically enhance the accumulation of Dox at tumor sites, thereby inhibiting and enhancing the anti-tumor effect. In summary, this study not only provides an efficient tumor-targeting delivery platform but also contributes to the improvement of chemotherapy–immunotherapy combination for tumor treatment strategy in the clinic.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"2016 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140940172","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 : 2024-04-12DOI: 10.1186/s12645-024-00259-1
Dan-dan Li, Jia-cheng Jin, Xuan-wen Liu, Shu-yang Liu, Fu-jian Ji, Tong Liu
Nanocarrier delivery of small interfering RNAs (siRNAs) to silence cancer-associated genes is a promising method for cancer treatment. Here, we explored the role and mechanisms of PLAG NPs-delivered si-Notch1 in colorectal cancer (CRC). High Notch1 expression was observed in both sensitive and resistant CRC tissues and cells. Notch1 silencing repressed proliferation and facilitates apoptosis of resistant CRC cells, and suppressed glycolysis and promoted pyroptosis in resistant CRC cells. Notch1 directly interacts with PCAF. Notch1 knockdown’s suppressive effect on glycolysis was reversed by overexpression of PCAF. Moreover, a nanocarrier called PLAG NPs was built with a higher delivery efficiency compared with lipo2000. Si-Notch1 delivered by PLAG NPs efficiently overcame the CRC cells’ 5-FU resistance and facilitated pyroptosis in a CRC mouse model. PLAG NPs carrying si-Notch1 had a great advantage in the extension of half-life circulation and targeting ability, providing a theoretical foundation for precise clinical treatment of CRC.
{"title":"Nanoparticle delivery of si-Notch1 modulates metabolic reprogramming to affect 5-FU resistance and cell pyroptosis in colorectal cancer","authors":"Dan-dan Li, Jia-cheng Jin, Xuan-wen Liu, Shu-yang Liu, Fu-jian Ji, Tong Liu","doi":"10.1186/s12645-024-00259-1","DOIUrl":"https://doi.org/10.1186/s12645-024-00259-1","url":null,"abstract":"Nanocarrier delivery of small interfering RNAs (siRNAs) to silence cancer-associated genes is a promising method for cancer treatment. Here, we explored the role and mechanisms of PLAG NPs-delivered si-Notch1 in colorectal cancer (CRC). High Notch1 expression was observed in both sensitive and resistant CRC tissues and cells. Notch1 silencing repressed proliferation and facilitates apoptosis of resistant CRC cells, and suppressed glycolysis and promoted pyroptosis in resistant CRC cells. Notch1 directly interacts with PCAF. Notch1 knockdown’s suppressive effect on glycolysis was reversed by overexpression of PCAF. Moreover, a nanocarrier called PLAG NPs was built with a higher delivery efficiency compared with lipo2000. Si-Notch1 delivered by PLAG NPs efficiently overcame the CRC cells’ 5-FU resistance and facilitated pyroptosis in a CRC mouse model. PLAG NPs carrying si-Notch1 had a great advantage in the extension of half-life circulation and targeting ability, providing a theoretical foundation for precise clinical treatment of CRC.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"121 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586129","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 : 2024-04-05DOI: 10.1186/s12645-024-00258-2
Fateme Momen Eslamiehei, Mansour Mashreghi, Maryam M. Matin
Colorectal cancer (CRC) ranks as the third most common cancer globally and the second leading cause of cancer-related mortality. Traditional chemotherapy, while effective, often results in significant side effects, highlighting the need for more efficient cancer therapies. Recent advancements in nanotechnology have led to the development of strategies that aim to minimize toxicity to normal cells by more precise targeting of cancer cells. In this context, cobalt oxide nanoparticles (Co3O4 NPs) have shown promising anticancer potential. Our study focuses on evaluating the antioxidant, antibacterial, and anticancer properties of Co3O4 NPs synthesized using Vibrio sp. VLC, a bioluminescent bacterium. XRD and FTIR analyses confirmed the successful synthesis of Co3O4 NPs, which displayed spherical morphology with an average diameter of 60 nm. The nanoparticles demonstrated significant antioxidant and antibacterial activities. The MTT assay indicated that the NPs caused dose- and time-dependent toxicity against CT26 cells, while exhibiting relatively lower toxicity towards normal cells. In vivo experiments further confirmed the significant tumor suppressive effects in BALB/c mice, with minimal side effects on the liver, spleen, and kidney tissues compared to the widespread toxicity of cisplatin. This study verifies the successful synthesis of Co3O4 NPs and their potent antioxidant, antibacterial, and anticancer activities. The biosynthesized Co3O4 NPs represent a promising targeted method for CRC therapy. However, further research is needed to elucidate their mechanism of action and also their application in the clinical phase.
{"title":"Advancing colorectal cancer therapy with biosynthesized cobalt oxide nanoparticles: a study on their antioxidant, antibacterial, and anticancer efficacy","authors":"Fateme Momen Eslamiehei, Mansour Mashreghi, Maryam M. Matin","doi":"10.1186/s12645-024-00258-2","DOIUrl":"https://doi.org/10.1186/s12645-024-00258-2","url":null,"abstract":"Colorectal cancer (CRC) ranks as the third most common cancer globally and the second leading cause of cancer-related mortality. Traditional chemotherapy, while effective, often results in significant side effects, highlighting the need for more efficient cancer therapies. Recent advancements in nanotechnology have led to the development of strategies that aim to minimize toxicity to normal cells by more precise targeting of cancer cells. In this context, cobalt oxide nanoparticles (Co3O4 NPs) have shown promising anticancer potential. Our study focuses on evaluating the antioxidant, antibacterial, and anticancer properties of Co3O4 NPs synthesized using Vibrio sp. VLC, a bioluminescent bacterium. XRD and FTIR analyses confirmed the successful synthesis of Co3O4 NPs, which displayed spherical morphology with an average diameter of 60 nm. The nanoparticles demonstrated significant antioxidant and antibacterial activities. The MTT assay indicated that the NPs caused dose- and time-dependent toxicity against CT26 cells, while exhibiting relatively lower toxicity towards normal cells. In vivo experiments further confirmed the significant tumor suppressive effects in BALB/c mice, with minimal side effects on the liver, spleen, and kidney tissues compared to the widespread toxicity of cisplatin. This study verifies the successful synthesis of Co3O4 NPs and their potent antioxidant, antibacterial, and anticancer activities. The biosynthesized Co3O4 NPs represent a promising targeted method for CRC therapy. However, further research is needed to elucidate their mechanism of action and also their application in the clinical phase. ","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"117 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586209","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 : 2024-04-02DOI: 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}
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