Pub Date : 2023-11-23DOI: 10.1186/s12645-023-00236-0
Rezvan Yazdian-Robati, Ehsan Amiri, Hossein Kamali, Aysun Khosravi, Seyed Mohammad Taghdisi, Mahmoud Reza Jaafari, Mohammad Mashreghi, Seyedeh Alia Moosavian
Although liposomes have improved patient safety and the pharmacokinetic profile of free drugs, their therapeutic efficacy has only shown marginal improvement. The incorporation of active-targeted ligands to enhance cellular uptake has shown promise in preclinical studies. However, no active-targeted liposomes have successfully translated into clinical use thus far. This study aimed to evaluate the targeting ability and antitumor efficiency of A6, a specific short peptide (KPSSPPEE) when incorporated into PEGylated liposomal doxorubicin (PLD). The results revealed significantly enhanced cellular uptake. The cytotoxicity of the formulations was determined by 3 h and 6 h incubation of formulations with cells, followed by 48 h incubation to evaluate the targeted ability of the formulations and the results indicated the higher cytotoxicity of A6-PLD (IC50 of 7.52 µg/mL after 6 h incubation) in the CD44 overexpressing C26 cell line compared to non-targeted PLD (IC50 of 15.02 µg/mL after 6 h incubation). However, CD44-negative NIH-3T3 cells exhibited similar uptake and in vitro cytotoxicity for both A6-PLD (IC50 of 38.05 µg/mL) and PLD (IC50 of 34.87 µg/mL). In animal studies, A6-PLD demonstrated significantly higher tumor localization of doxorubicin (Dox) (~ 8 and 15 µg Dox/g tumor for 24 and 48 after injection) compared to PLD (~ 6 and 8 µg Dox/g tumor for 24 and 48 after injection), resulting in effective inhibition of tumor growth. The median survival time (MST) for Dextrose 5% was 10, PLD was 14 and A6-PLD was 22 days. In conclusion, A6-PLD, a simple and effective targeted liposome formulation, exhibits high potential for clinical translation. Its improved targetability and antitumor efficacy make it a promising candidate for future clinical applications.
{"title":"CD44-specific short peptide A6 boosts cellular uptake and anticancer efficacy of PEGylated liposomal doxorubicin in vitro and in vivo","authors":"Rezvan Yazdian-Robati, Ehsan Amiri, Hossein Kamali, Aysun Khosravi, Seyed Mohammad Taghdisi, Mahmoud Reza Jaafari, Mohammad Mashreghi, Seyedeh Alia Moosavian","doi":"10.1186/s12645-023-00236-0","DOIUrl":"https://doi.org/10.1186/s12645-023-00236-0","url":null,"abstract":"Although liposomes have improved patient safety and the pharmacokinetic profile of free drugs, their therapeutic efficacy has only shown marginal improvement. The incorporation of active-targeted ligands to enhance cellular uptake has shown promise in preclinical studies. However, no active-targeted liposomes have successfully translated into clinical use thus far. This study aimed to evaluate the targeting ability and antitumor efficiency of A6, a specific short peptide (KPSSPPEE) when incorporated into PEGylated liposomal doxorubicin (PLD). The results revealed significantly enhanced cellular uptake. The cytotoxicity of the formulations was determined by 3 h and 6 h incubation of formulations with cells, followed by 48 h incubation to evaluate the targeted ability of the formulations and the results indicated the higher cytotoxicity of A6-PLD (IC50 of 7.52 µg/mL after 6 h incubation) in the CD44 overexpressing C26 cell line compared to non-targeted PLD (IC50 of 15.02 µg/mL after 6 h incubation). However, CD44-negative NIH-3T3 cells exhibited similar uptake and in vitro cytotoxicity for both A6-PLD (IC50 of 38.05 µg/mL) and PLD (IC50 of 34.87 µg/mL). In animal studies, A6-PLD demonstrated significantly higher tumor localization of doxorubicin (Dox) (~ 8 and 15 µg Dox/g tumor for 24 and 48 after injection) compared to PLD (~ 6 and 8 µg Dox/g tumor for 24 and 48 after injection), resulting in effective inhibition of tumor growth. The median survival time (MST) for Dextrose 5% was 10, PLD was 14 and A6-PLD was 22 days. In conclusion, A6-PLD, a simple and effective targeted liposome formulation, exhibits high potential for clinical translation. Its improved targetability and antitumor efficacy make it a promising candidate for future clinical applications.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"40 3","pages":""},"PeriodicalIF":5.7,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138503622","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}
Abstract Background Immune checkpoint blockade (ICB) has achieved unprecedented success in inhibiting the progression and metastasis of many cancers. However, ICB regents as a single treatment have a relatively low overall response rate due to the tumor’s low immunogenicity and immunosuppressive microenvironment. Herein, we report a PD-1 cellular membrane-coated ferroptosis nanoinducer to potentiate cancer immunotherapy toward triple-negative breast cancer. Results This study demonstrates that PD-1 membrane-coated RSL3 nanoparticles (PD-1@RSL3 NPs) have the ability to disrupt the PD-1/PD-L1 axis, leading to the activation of antitumor immunity in breast cancer. In addition, the nanoparticles promote the induction of tumor cell ferroptosis through GPX4 inhibition, enhanced infiltration of CD8 + T cells, and maturation of dendritic cells. The potentiated antitumor immune response induced by PD-1@RSL3 NPs significantly delayed tumor progression and extended the survival rate of mice with breast cancer xenografts. Conclusions Our study suggest the potential of PD-1@RSL3 NPs as an effective therapeutic approach for breast cancer by promoting tumor cell ferroptosis and inducing antitumor immunity.
{"title":"Enhanced cancer immunotherapy through synergistic ferroptosis and immune checkpoint blockade using cell membrane-coated nanoparticles","authors":"Yeteng Mu, Yuxin Fan, Lianping He, Nannan Hu, Han Xue, Xingang Guan, Zhijian Zheng","doi":"10.1186/s12645-023-00234-2","DOIUrl":"https://doi.org/10.1186/s12645-023-00234-2","url":null,"abstract":"Abstract Background Immune checkpoint blockade (ICB) has achieved unprecedented success in inhibiting the progression and metastasis of many cancers. However, ICB regents as a single treatment have a relatively low overall response rate due to the tumor’s low immunogenicity and immunosuppressive microenvironment. Herein, we report a PD-1 cellular membrane-coated ferroptosis nanoinducer to potentiate cancer immunotherapy toward triple-negative breast cancer. Results This study demonstrates that PD-1 membrane-coated RSL3 nanoparticles (PD-1@RSL3 NPs) have the ability to disrupt the PD-1/PD-L1 axis, leading to the activation of antitumor immunity in breast cancer. In addition, the nanoparticles promote the induction of tumor cell ferroptosis through GPX4 inhibition, enhanced infiltration of CD8 + T cells, and maturation of dendritic cells. The potentiated antitumor immune response induced by PD-1@RSL3 NPs significantly delayed tumor progression and extended the survival rate of mice with breast cancer xenografts. Conclusions Our study suggest the potential of PD-1@RSL3 NPs as an effective therapeutic approach for breast cancer by promoting tumor cell ferroptosis and inducing antitumor immunity.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"41 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136347564","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 : 2023-11-01DOI: 10.1186/s12645-023-00233-3
Weiwei Sun, Pingwei Xu, Pengtao Pan, Sheng Guo, Rui Liu, Guojie Ji, Huanhuan Hu, Weidong Li, Lili Dai
Abstract Tumor microparticles (T-MPs) are vesicles released from tumor cells when they receive apoptotic or stimuli signals. T-MPs, which contain some proteins, lipids and nucleic acids from tumor cells, contribute to the exchange of material, energy and information between cells. T-MPs contain both tumor antigens and innate immunostimulatory signals, making T-MPs as a new form of tumor vaccine. Meanwhile, T-MPs can be used as natural carriers to transport ‘‘cargoes’’, such as chemotherapy drugs, oncolytic viruses, nucleic acids, and metal nanoparticles to treat tumors. In addition, T-MPs enhance the effect of chemotherapy. This review introduces the application of T-MPs as vaccines, delivery systems and chemosensitizers in tumor prevention and treatment, with a focus on the mechanisms, clinical applications, and influencing factors of drug-loaded T-MPs in tumor treatment.
{"title":"Application of tumor microparticles in tumor prevention and treatment","authors":"Weiwei Sun, Pingwei Xu, Pengtao Pan, Sheng Guo, Rui Liu, Guojie Ji, Huanhuan Hu, Weidong Li, Lili Dai","doi":"10.1186/s12645-023-00233-3","DOIUrl":"https://doi.org/10.1186/s12645-023-00233-3","url":null,"abstract":"Abstract Tumor microparticles (T-MPs) are vesicles released from tumor cells when they receive apoptotic or stimuli signals. T-MPs, which contain some proteins, lipids and nucleic acids from tumor cells, contribute to the exchange of material, energy and information between cells. T-MPs contain both tumor antigens and innate immunostimulatory signals, making T-MPs as a new form of tumor vaccine. Meanwhile, T-MPs can be used as natural carriers to transport ‘‘cargoes’’, such as chemotherapy drugs, oncolytic viruses, nucleic acids, and metal nanoparticles to treat tumors. In addition, T-MPs enhance the effect of chemotherapy. This review introduces the application of T-MPs as vaccines, delivery systems and chemosensitizers in tumor prevention and treatment, with a focus on the mechanisms, clinical applications, and influencing factors of drug-loaded T-MPs in tumor treatment.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"66 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135321455","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 : 2023-10-21DOI: 10.1186/s12645-023-00232-4
Dengyun Nie, Ting Guo, Xinyu Zong, Wenya Li, Yinxing Zhu, Miao Yue, Min Sha, Mei Lin
Abstract Artesunate (ART) has great value in the field of tumor therapy. Interestingly, in this study, we found that ART could obviously induce ferroptosis in hepatocellular carcinoma (HCC) cells, but its low water solubility and bioavailability limited its application potential. Hence, we synthesized ART-loaded mesoporous silica nanoparticles (MSNs) conjugated with folic acid (FA) (MSN-ART-FA) with tumor-targeting performance and assessed their characteristics. We evaluated the ability of MSN-ART and MSN-ART-FA to induce ferroptosis of hepatoma cells via testing levels of reactive oxygen species (ROS), Fe 2+ , malondialdehyde (MDA) and glutathione (GSH), observation of mitochondrial morphology, as well as the expression of key proteins in ferroptosis. The results showed that prepared MSN-ART and MSN-ART-FA could remarkedly improve the bioavailability of ART to enhance ferroptosis, thereby inhibiting cell proliferation, migration and invasion in vitro. Besides, MSN-ART-FA group displayed slower tumor growth and smaller tumor volumes than MSN-ART group in HepG2 xenograft mouse model. It provided a potential therapeutic option for HCC and expanded the horizon for the clinical treatment of other cancers. Graphical Abstract
青蒿琥酯(ART)在肿瘤治疗领域具有重要的应用价值。有趣的是，在本研究中，我们发现ART能明显诱导肝癌细胞铁下垂，但其低水溶性和生物利用度限制了其应用潜力。因此，我们合成了具有肿瘤靶向性能的载art偶联叶酸(FA)的介孔二氧化硅纳米颗粒(MSNs - art -FA)，并评估了它们的特性。我们通过检测活性氧(ROS)、Fe 2+、丙二醛(MDA)和谷胱甘肽(GSH)水平、观察线粒体形态以及铁下垂关键蛋白的表达来评估MSN-ART和MSN-ART- fa诱导肝癌细胞铁下垂的能力。结果表明，制备的MSN-ART和MSN-ART- fa可显著提高ART的生物利用度，增强铁下垂，从而抑制细胞的体外增殖、迁移和侵袭。此外，在HepG2异种移植小鼠模型中，MSN-ART- fa组肿瘤生长速度较MSN-ART组慢，肿瘤体积较小。它为肝癌提供了一种潜在的治疗选择，并扩大了其他癌症的临床治疗范围。图形抽象
{"title":"Induction of ferroptosis by artesunate nanoparticles is an effective therapeutic strategy for hepatocellular carcinoma","authors":"Dengyun Nie, Ting Guo, Xinyu Zong, Wenya Li, Yinxing Zhu, Miao Yue, Min Sha, Mei Lin","doi":"10.1186/s12645-023-00232-4","DOIUrl":"https://doi.org/10.1186/s12645-023-00232-4","url":null,"abstract":"Abstract Artesunate (ART) has great value in the field of tumor therapy. Interestingly, in this study, we found that ART could obviously induce ferroptosis in hepatocellular carcinoma (HCC) cells, but its low water solubility and bioavailability limited its application potential. Hence, we synthesized ART-loaded mesoporous silica nanoparticles (MSNs) conjugated with folic acid (FA) (MSN-ART-FA) with tumor-targeting performance and assessed their characteristics. We evaluated the ability of MSN-ART and MSN-ART-FA to induce ferroptosis of hepatoma cells via testing levels of reactive oxygen species (ROS), Fe 2+ , malondialdehyde (MDA) and glutathione (GSH), observation of mitochondrial morphology, as well as the expression of key proteins in ferroptosis. The results showed that prepared MSN-ART and MSN-ART-FA could remarkedly improve the bioavailability of ART to enhance ferroptosis, thereby inhibiting cell proliferation, migration and invasion in vitro. Besides, MSN-ART-FA group displayed slower tumor growth and smaller tumor volumes than MSN-ART group in HepG2 xenograft mouse model. It provided a potential therapeutic option for HCC and expanded the horizon for the clinical treatment of other cancers. Graphical Abstract","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135512321","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 : 2023-10-16DOI: 10.1186/s12645-023-00226-2
Pramod C. Mane, Deepali D. Kadam, Ashok N. Khadse, Aditya R. Chaudhari, Supriya P. Ughade, Sachin B. Agawane, Ravindra D. Chaudhari
Abstract Background In the present era, we are facing different health problems mainly concerning with drug resistance in microorganisms as well as in cancer cells. In addition, we are also facing the problems of controlling oxidative stress and insect originated diseases like dengue, malaria, chikungunya, etc. originated from mosquitoes. In this investigation, we unfurled the potential of Achatina fulica mucus in green synthesis of mucus mediated copper oxide bio-nanocomposites (SM-CuONC) and cobalt oxide bio-nanocomposites (SM-Co 3 O 4 NC). Herein we carried out the physico-chemical characterization like UV–Vis spectra, X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Transmission electron microscopy (TEM), Energy Dispersive X-ray Analysis (EDAX) and X-ray photoelectron spectroscopy ( XPS) of as synthesized bio-nanocomposites. Both the bio-nanocomposites were tested for their potential as antimicrobial activity using well diffusion assay, anticancer activity by MTT assay, antioxidant activity by phosphomolybdenum assay and mosquito larvicidal activity. Results The results of this study revealed that, SM-CuONC and SM-Co 3 O 4 NC were synthesized successfully using A. fulica mucus. The FESEM and TEM data reveal the formation of nanoparticles with quasi-spherical morphology and average particle size of ~ 18 nm for both nanocomposites. The EDAX peak confirms the presence of elemental copper and cobalt in the analyzed samples. The X-ray diffraction analysis confirmed the crystalline nature of the CuO and Co 3 O 4 . The result of anti microbial study exhibited that, SM-CuONC showed maximum antimicrobial activity against Escherichia coli NCIM 2065 and Aspergillus fumigatus NCIM 902 which were noted as 2.36 ± 0.31 and 2.36 ± 0.59 cm resp. at 60 µg/well concentration. The result of anticancer activity for SM-CuONC was exhibited as, 68.66 ± 3.72, 62.66 ± 3.61 and 71.00 ± 2.36 percent kill, while SM-Co 3 O 4 NC exhibited 61.00 ± 3.57, 72.66 ± 4.50 and 71.66 ± 4.22 percent kill against Human colon cancer (HCT-15), Cervical cancer (HeLa), and Breast cancer (MDA-MB-231) cell lines, respectively, at 20 µg/well concentration. Both the nanocomposites also exhibited better antioxidant activity. Total antioxidant activity for SM-CuONC at 50 µg/ml concentration was found to be highest as 55.33 ± 3.72 while that of SM-Co 3 O 4 Ns was 52.00 ± 3.22 mM of ascorbic acid/µg respectively. Both bio-nanocomposites also exhibited 100% mosquito larvicidal activity at concentration ranging from 40 to 50 mg/l. During cytotoxicity study it is noted that at 5 µg/well concentration, SM-CuO and SM-Co 3 O 4 NCs suspension showed more than 97% viability of normal (L929) cell lines. We also studied phytotoxicity of both bio-nanocomposites on Triticum aestivum . In this study, 100% seed germination was observed when seeds are treated with SM-CuONC and SM-Co 3 O 4 NC at 500 mg/l and 250 mg/l concentration respectively. Conclusions This study concludes that
摘要背景在当今时代，我们面临着不同的健康问题，主要涉及微生物的耐药性以及癌细胞的耐药性。此外，我们还面临着控制氧化应激和蚊源性登革热、疟疾、基孔肯雅热等虫源性疾病的问题。在这项研究中，我们揭示了黄斑黄芪粘液在绿色合成粘液介导的氧化铜生物纳米复合材料(SM-CuONC)和氧化钴生物纳米复合材料(sm - co3o4nc)中的潜力。本文对合成的生物纳米复合材料进行了紫外可见光谱、x射线衍射(XRD)、场发射扫描电镜(FESEM)、透射电镜(TEM)、能量色散x射线分析(EDAX)和x射线光电子能谱(XPS)等理化表征。采用孔扩散法、MTT法、钼磷法和杀蚊法测定了两种生物纳米复合材料的抗菌活性、抗癌活性和抗氧化活性。结果利用黄颡鱼黏液成功合成了SM-CuONC和sm - co3o4nc。FESEM和TEM数据表明，两种纳米复合材料均形成了准球形的纳米颗粒，平均粒径约为18 nm。EDAX峰证实了分析样品中铜和钴元素的存在。x射线衍射分析证实了CuO和co3o4的结晶性质。抑菌实验结果表明，SM-CuONC对大肠杆菌NCIM 2065和烟曲霉NCIM 902的抑菌活性最高，分别为2.36±0.31和2.36±0.59 cm。浓度为60µg/孔。在20µg/孔浓度下，SM-CuONC对人结肠癌(HCT-15)、宫颈癌(HeLa)和乳腺癌(MDA-MB-231)细胞株的杀伤率分别为68.66±3.72、62.66±3.61和71.00±2.36%，sm - co3o4nc对人结肠癌(HCT-15)、宫颈癌(HeLa)和乳腺癌(MDA-MB-231)的杀伤率分别为61.00±3.57、72.66±4.50和71.66±4.22%。两种纳米复合材料均表现出较好的抗氧化活性。在50µg/ml浓度下，SM-CuONC的总抗氧化活性最高，分别为55.33±3.72 mM /µg, sm - co3o4ns的总抗氧化活性最高，分别为52.00±3.22 mM /µg。在40 ~ 50 mg/l的浓度范围内，两种生物纳米复合材料均表现出100%的灭蚊活性。在细胞毒性研究中，我们注意到在5µg/孔浓度下，SM-CuO和sm - co3o4ncs悬浮液对正常(L929)细胞株的存活率超过97%。我们还研究了两种生物纳米复合材料对小麦的植物毒性。在本研究中，SM-CuONC和sm - co3o4nc分别以500 mg/l和250 mg/l的浓度处理种子时，种子萌发率达到100%。结论合成的SM-CuONC和sm - co3o4nc均具有较好的抗菌、抗癌、抗氧化和杀蚊潜能，可用于制药、卫生保健等领域，提高人类生活质量。
{"title":"Green adeptness in synthesis of non-toxic copper and cobalt oxide nanocomposites with multifaceted bioactivities","authors":"Pramod C. Mane, Deepali D. Kadam, Ashok N. Khadse, Aditya R. Chaudhari, Supriya P. Ughade, Sachin B. Agawane, Ravindra D. Chaudhari","doi":"10.1186/s12645-023-00226-2","DOIUrl":"https://doi.org/10.1186/s12645-023-00226-2","url":null,"abstract":"Abstract Background In the present era, we are facing different health problems mainly concerning with drug resistance in microorganisms as well as in cancer cells. In addition, we are also facing the problems of controlling oxidative stress and insect originated diseases like dengue, malaria, chikungunya, etc. originated from mosquitoes. In this investigation, we unfurled the potential of Achatina fulica mucus in green synthesis of mucus mediated copper oxide bio-nanocomposites (SM-CuONC) and cobalt oxide bio-nanocomposites (SM-Co 3 O 4 NC). Herein we carried out the physico-chemical characterization like UV–Vis spectra, X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Transmission electron microscopy (TEM), Energy Dispersive X-ray Analysis (EDAX) and X-ray photoelectron spectroscopy ( XPS) of as synthesized bio-nanocomposites. Both the bio-nanocomposites were tested for their potential as antimicrobial activity using well diffusion assay, anticancer activity by MTT assay, antioxidant activity by phosphomolybdenum assay and mosquito larvicidal activity. Results The results of this study revealed that, SM-CuONC and SM-Co 3 O 4 NC were synthesized successfully using A. fulica mucus. The FESEM and TEM data reveal the formation of nanoparticles with quasi-spherical morphology and average particle size of ~ 18 nm for both nanocomposites. The EDAX peak confirms the presence of elemental copper and cobalt in the analyzed samples. The X-ray diffraction analysis confirmed the crystalline nature of the CuO and Co 3 O 4 . The result of anti microbial study exhibited that, SM-CuONC showed maximum antimicrobial activity against Escherichia coli NCIM 2065 and Aspergillus fumigatus NCIM 902 which were noted as 2.36 ± 0.31 and 2.36 ± 0.59 cm resp. at 60 µg/well concentration. The result of anticancer activity for SM-CuONC was exhibited as, 68.66 ± 3.72, 62.66 ± 3.61 and 71.00 ± 2.36 percent kill, while SM-Co 3 O 4 NC exhibited 61.00 ± 3.57, 72.66 ± 4.50 and 71.66 ± 4.22 percent kill against Human colon cancer (HCT-15), Cervical cancer (HeLa), and Breast cancer (MDA-MB-231) cell lines, respectively, at 20 µg/well concentration. Both the nanocomposites also exhibited better antioxidant activity. Total antioxidant activity for SM-CuONC at 50 µg/ml concentration was found to be highest as 55.33 ± 3.72 while that of SM-Co 3 O 4 Ns was 52.00 ± 3.22 mM of ascorbic acid/µg respectively. Both bio-nanocomposites also exhibited 100% mosquito larvicidal activity at concentration ranging from 40 to 50 mg/l. During cytotoxicity study it is noted that at 5 µg/well concentration, SM-CuO and SM-Co 3 O 4 NCs suspension showed more than 97% viability of normal (L929) cell lines. We also studied phytotoxicity of both bio-nanocomposites on Triticum aestivum . In this study, 100% seed germination was observed when seeds are treated with SM-CuONC and SM-Co 3 O 4 NC at 500 mg/l and 250 mg/l concentration respectively. Conclusions This study concludes that ","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136114278","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 : 2023-10-06DOI: 10.1186/s12645-023-00229-z
Elsayed I. Salim, Magdy E. Mahfouz, Eman A. Eltonouby, Nemany A. N. Hanafy, Ezar H. Hafez
Abstract Bee pollen extract (BPE)-based polymer nanoparticles (BPENP) were fabricated using bovine serum albumin (BSA) and targeted with folic acid and were further characterized. Mice groups are: Group 1 received saline, whereas Groups 2, 3, 4, 5, and 6 received a single dose of urethane, followed by weekly injections of butylated hydroxy-toluene (BHT). After the BHT injection, the mice in Groups 3, 4, 5, and 6 received BPE, Avastin, BPENP, and BPENP + Avastin, respectively. The number and size of tumors were decreased in Group 6 compared to those in the other groups. The ratios of early and late apoptotic cells in Groups 3, 4, 5, and 6 (42.8%, 41.4%, 26.2%, and 45.4%, respectively) were higher than that in the untreated group. The PCNA-labeling indexes (LI)% in tissues and lesions from Group 6 were lower than those in the other groups; on the other hand, the Caspase-3 LI (%) was higher than those in the other groups. No significant differences in HRAS and MAPK levels were observed between Group 6 and the other groups. However, the level of Bax was significantly increased, whereas those of Bcl2 and P21 were decreased in Group 6 compared to those in Groups 4 and 5. According to the results of the current study's in vivo lung cancer mouse model, adjuvant chemotherapy given in conjunction with a polyphenolic substance derived from bee pollen significantly activates the apoptotic pathways as measured by flow cytometry, immunohistochemistry, and apoptotic genes. It also significantly reduces tumor volume and growth as measured by histopathology. Graphical Abstract
{"title":"Based polymer nanoparticles from bee pollen attenuate non-small lung cancer through enhancement of apoptosis and cell cycle arrest in vivo","authors":"Elsayed I. Salim, Magdy E. Mahfouz, Eman A. Eltonouby, Nemany A. N. Hanafy, Ezar H. Hafez","doi":"10.1186/s12645-023-00229-z","DOIUrl":"https://doi.org/10.1186/s12645-023-00229-z","url":null,"abstract":"Abstract Bee pollen extract (BPE)-based polymer nanoparticles (BPENP) were fabricated using bovine serum albumin (BSA) and targeted with folic acid and were further characterized. Mice groups are: Group 1 received saline, whereas Groups 2, 3, 4, 5, and 6 received a single dose of urethane, followed by weekly injections of butylated hydroxy-toluene (BHT). After the BHT injection, the mice in Groups 3, 4, 5, and 6 received BPE, Avastin, BPENP, and BPENP + Avastin, respectively. The number and size of tumors were decreased in Group 6 compared to those in the other groups. The ratios of early and late apoptotic cells in Groups 3, 4, 5, and 6 (42.8%, 41.4%, 26.2%, and 45.4%, respectively) were higher than that in the untreated group. The PCNA-labeling indexes (LI)% in tissues and lesions from Group 6 were lower than those in the other groups; on the other hand, the Caspase-3 LI (%) was higher than those in the other groups. No significant differences in HRAS and MAPK levels were observed between Group 6 and the other groups. However, the level of Bax was significantly increased, whereas those of Bcl2 and P21 were decreased in Group 6 compared to those in Groups 4 and 5. According to the results of the current study's in vivo lung cancer mouse model, adjuvant chemotherapy given in conjunction with a polyphenolic substance derived from bee pollen significantly activates the apoptotic pathways as measured by flow cytometry, immunohistochemistry, and apoptotic genes. It also significantly reduces tumor volume and growth as measured by histopathology. Graphical Abstract","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135350773","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}
Abstract Background PEGylated nanoparticles (PEG-NPs) are not effective for hematologic malignancies as they lack the enhanced permeability and retention effect (EPR effect). Tumor-targeted PEG-NPs can systemically track lymphoma and actively internalize into cancer cells to enhance therapeutic efficacy. We generated an anti-PEG bispecific antibody (BsAb; mPEG × CD20) which was able to simultaneously bind to methoxy PEG on liposomes and CD20 to form multivalent αCD20-armed liposomes. This αCD20-armed liposome was able to crosslink CD20 on lymphoma cells to enhance cellular internalization and the anti-cancer efficacy of the liposomes to lymphoma. We generated mPEG × CD20 and used this bispecific antibody to modify PEGylated liposomal doxorubicin (PLD) through a one-step formulation. Results αCD20-armed PLD (αCD20/PLD) specifically targeted CD20 + Raji cells and enhanced PLD internalization 56-fold after 24 h. αCD20/PLD also increased cytotoxicity to Raji cells by 15.2-fold in comparison with PLD and control mPEG × DNS-modified PLD (αDNS/PLD). mPEG × CD20 significantly enhanced the tumor accumulation 2.8-fold in comparison with mPEG × DNS-conjugated PEGylated liposomal DiD in Raji tumors. Moreover, αCD20/PLD had significantly greater therapeutic efficacy as compared to αDNS/PLD ( P < 0.0001) and PLD( P < 0.0001), and αCD20/PLD-treated mice had a 90% survival rate at 100-day post-treatment. Conclusions Modification of mPEG × CD20 can confer PLD with CD20 specificity to enhance the internalization and the anti-cancer efficacy of PEG-NPs. This therapeutic strategy can conveniently be used to modify various PEG-NPs with anti-PEG BsAb to overcome the lack of EPR effect of hematologic malignancies and improve therapeutic efficacy.
{"title":"Targeting and internalizing PEGylated nanodrugs to enhance the therapeutic efficacy of hematologic malignancies by anti-PEG bispecific antibody (mPEG × CD20)","authors":"Huei-Jen Chen, Yi-An Cheng, Yu-Tung Chen, Chia-Ching Li, Bo-Cheng Huang, Shih-Ting Hong, I.-Ju Chen, Kai-Wen Ho, Chiao-Yun Chen, Fang-Ming Chen, Jaw-Yuan Wang, Steve R. Roffler, Tian-Lu Cheng, Dung-Ho Wu","doi":"10.1186/s12645-023-00230-6","DOIUrl":"https://doi.org/10.1186/s12645-023-00230-6","url":null,"abstract":"Abstract Background PEGylated nanoparticles (PEG-NPs) are not effective for hematologic malignancies as they lack the enhanced permeability and retention effect (EPR effect). Tumor-targeted PEG-NPs can systemically track lymphoma and actively internalize into cancer cells to enhance therapeutic efficacy. We generated an anti-PEG bispecific antibody (BsAb; mPEG × CD20) which was able to simultaneously bind to methoxy PEG on liposomes and CD20 to form multivalent αCD20-armed liposomes. This αCD20-armed liposome was able to crosslink CD20 on lymphoma cells to enhance cellular internalization and the anti-cancer efficacy of the liposomes to lymphoma. We generated mPEG × CD20 and used this bispecific antibody to modify PEGylated liposomal doxorubicin (PLD) through a one-step formulation. Results αCD20-armed PLD (αCD20/PLD) specifically targeted CD20 + Raji cells and enhanced PLD internalization 56-fold after 24 h. αCD20/PLD also increased cytotoxicity to Raji cells by 15.2-fold in comparison with PLD and control mPEG × DNS-modified PLD (αDNS/PLD). mPEG × CD20 significantly enhanced the tumor accumulation 2.8-fold in comparison with mPEG × DNS-conjugated PEGylated liposomal DiD in Raji tumors. Moreover, αCD20/PLD had significantly greater therapeutic efficacy as compared to αDNS/PLD ( P < 0.0001) and PLD( P < 0.0001), and αCD20/PLD-treated mice had a 90% survival rate at 100-day post-treatment. Conclusions Modification of mPEG × CD20 can confer PLD with CD20 specificity to enhance the internalization and the anti-cancer efficacy of PEG-NPs. This therapeutic strategy can conveniently be used to modify various PEG-NPs with anti-PEG BsAb to overcome the lack of EPR effect of hematologic malignancies and improve therapeutic efficacy.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135350774","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}
Abstract Background Engineering nanotherapeutics have been extensively studied for cancer therapy. However, the therapeutic efficacy is still severely restricted by biophysiological barriers and intracellular accumulation. Although the biomimetic nanoparticles have improved the former issue, there is almost no breakthrough in researches of intracellular transport. Herein, we proposed a NIR-responsive nuclear-targeted hybrid membrane biomimetic Prussian blue drug-loading nanotherapeutics (PB@DN@M). Results The hybrid membrane coating bestows nanotherapeutics tumor targeting and immune escape ability, thus promoting the tumor enrichment of PB nanotherapeutics. The nuclear targeting function triggered by NIR enhances the cellular internalization and nuclear entry efficiency, resulting in a superadditive effect for boosting photothermal-chemotherapy efficacy. Moreover, taking advantage of non-interference Raman properties of PB, we can track the location and distribution of nanotherapeutics, which is beneficial for guiding precise synchronization of photothermal-chemotherapy. The results revealed that this PB@DN@M presented a remarkable therapeutic efficacy and significantly inhibited the tumor growth up to 87.17%. Conclusions Therefore, this spatiotemporal controllable biomimetic nanotherapeutics will provide a new insight and strategy for specific targeted therapy of tumors.
{"title":"Boosting nuclear-targeted photothermal-chemotherapy by NIR-responsive hybrid membrane camouflaged nanotherapeutics","authors":"Xinyue Xing, Yuying Zeng, Wanqing Zhong, Wendai Cheng, Chengxin Zhou, Xiaoxu Lu, Liyun Zhong","doi":"10.1186/s12645-023-00224-4","DOIUrl":"https://doi.org/10.1186/s12645-023-00224-4","url":null,"abstract":"Abstract Background Engineering nanotherapeutics have been extensively studied for cancer therapy. However, the therapeutic efficacy is still severely restricted by biophysiological barriers and intracellular accumulation. Although the biomimetic nanoparticles have improved the former issue, there is almost no breakthrough in researches of intracellular transport. Herein, we proposed a NIR-responsive nuclear-targeted hybrid membrane biomimetic Prussian blue drug-loading nanotherapeutics (PB@DN@M). Results The hybrid membrane coating bestows nanotherapeutics tumor targeting and immune escape ability, thus promoting the tumor enrichment of PB nanotherapeutics. The nuclear targeting function triggered by NIR enhances the cellular internalization and nuclear entry efficiency, resulting in a superadditive effect for boosting photothermal-chemotherapy efficacy. Moreover, taking advantage of non-interference Raman properties of PB, we can track the location and distribution of nanotherapeutics, which is beneficial for guiding precise synchronization of photothermal-chemotherapy. The results revealed that this PB@DN@M presented a remarkable therapeutic efficacy and significantly inhibited the tumor growth up to 87.17%. Conclusions Therefore, this spatiotemporal controllable biomimetic nanotherapeutics will provide a new insight and strategy for specific targeted therapy of tumors.","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135739013","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 : 2023-09-07DOI: 10.1186/s12645-023-00225-3
C. Nascimento, Naiara Clemente Tavares, Izabella C. A. Batista, Mônica Maria Magalhães Caetano, E. D. de Oliveira, Stella Garcia Colombarolli, Anna Carolina Pinheiro Lage, Rodrigo Corrêa-Oliveira, Érica Alessandra Rocha Alves, Celso Pinto de Melo, C. E. Calzavara-Silva
{"title":"Iron oxide polyaniline-coated nanoparticles modulate tumor microenvironment in breast cancer: an in vitro study on the reprogramming of tumor-associated macrophages","authors":"C. Nascimento, Naiara Clemente Tavares, Izabella C. A. Batista, Mônica Maria Magalhães Caetano, E. D. de Oliveira, Stella Garcia Colombarolli, Anna Carolina Pinheiro Lage, Rodrigo Corrêa-Oliveira, Érica Alessandra Rocha Alves, Celso Pinto de Melo, C. E. Calzavara-Silva","doi":"10.1186/s12645-023-00225-3","DOIUrl":"https://doi.org/10.1186/s12645-023-00225-3","url":null,"abstract":"","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49631497","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 : 2023-09-04DOI: 10.1186/s12645-023-00223-5
Ashique Al Hoque, Debasmita Dutta, B. Paul, Leena Kumari, Iman Ehsan, Moumita Dhara, Biswajit Mukherjee, Mohiuddin Quadir, Benny A. Kaipparettu, Soumik Laha, Shantanu Ganguly
{"title":"ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation","authors":"Ashique Al Hoque, Debasmita Dutta, B. Paul, Leena Kumari, Iman Ehsan, Moumita Dhara, Biswajit Mukherjee, Mohiuddin Quadir, Benny A. Kaipparettu, Soumik Laha, Shantanu Ganguly","doi":"10.1186/s12645-023-00223-5","DOIUrl":"https://doi.org/10.1186/s12645-023-00223-5","url":null,"abstract":"","PeriodicalId":9408,"journal":{"name":"Cancer Nanotechnology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49394529","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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