Pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy
Muhammad Kashif Riaz,1 Xue Zhang,1 Ka Hong Wong,1 Huoji Chen,2 Qiang Liu,2 Xiaoyu Chen,1 Ge Zhang,1 Aiping Lu,1,3 Zhijun Yang1,31School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical Univer...
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Dove Medical Press
2019
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oai:doaj.org-article:e864699d64274dc7b29d062d30a59a642021-12-02T09:49:00ZPulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy1178-2013https://doaj.org/article/e864699d64274dc7b29d062d30a59a642019-04-01T00:00:00Zhttps://www.dovepress.com/pulmonary-delivery-of-transferrin-receptors-targeting-peptide-surface--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Muhammad Kashif Riaz,1 Xue Zhang,1 Ka Hong Wong,1 Huoji Chen,2 Qiang Liu,2 Xiaoyu Chen,1 Ge Zhang,1 Aiping Lu,1,3 Zhijun Yang1,31School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Changshu Research Institute, Hong Kong Baptist University, Changshu Economic and Technological Development (CETD) Zone, Changshu, Jiangsu Province, People’s Republic of ChinaPurpose: Lung cancer has a high incidence rate worldwide with a 5-year survival rate of 18%, and is the leading cause of cancer-related deaths. The aim of this study is to augment therapeutic efficacy of quercetin (QR) for lung cancer therapy by targeting transferrin receptors, which are overexpressed and confined to tumor cells.Methods: In this study, T7 surface-functionalized liposomes loaded with QR (T7-QR-lip) having different T7 peptide densities (0.5%, 1% and 2%) were prepared by the film hydration method. T7 surface-functionalized liposomes were characterized and evaluated in terms of in vitro cytotoxicity and cellular uptake, 3D tumor spheroid penetration and inhibition capabilities, in vivo biodistribution and therapeutic efficacy in mice with orthotopic lung-tumor implantation by fluorescent and bioluminescent imaging via pulmonary administration.Results: In vitro, 2% T7-QR-lip exhibited significantly augmented cytotoxicity (∼3-fold), higher apoptosis induction and S-phase cell-cycle arrest. A prominent peak right-shift and enhanced mean fluorescence intensity was observed in A549 cells treated with T7 Coumarin-6 liposomes (T7-Cou6-lip), confirming the target specificity of T7 targeted liposomes; while, after treatment with T7-QR-lip and non-targeted QR-lip, no significant difference was observed in cellular uptake and in vitro cytotoxicity studies in MRC-5 (normal lung fibroblast) cells. T7-Cou6-lip showed higher fluorescence intensity in A549 cells and a significantly deeper penetration depth of 120 μm in the core of the tumor spheroids and T7-QR-lip produced significantly higher tumor-spheroid growth inhibition. The in vivo biodistribution study via pulmonary delivery of T7 1,1’-dioctadecyltetramethyl-indotricarbocyanine iodide liposomes demonstrated liposome accumulation in the lungs and sustained-release behavior up to 96 h. Further, T7-QR-lip significantly enhanced the anticancer activity of QR and lifespan of mice (p<0.01, compared with saline) in orthotopic lung tumor-bearing mice via pulmonary administration.Conclusion: T7 surface-functionalized liposomes provide a potential drug delivery system for a range of anticancer drugs to enhance their therapeutic efficacy by localized (pulmonary) administration and targeted delivery.Keywords: Quercetin, lung cancer, surface-functionalized liposomes, T7 peptide, orthotopic lung cancer model, pulmonary deliveryRiaz MKZhang XWong KHChen HLiu QChen XZhang GLu AYang ZDove Medical PressarticleQuercetinlung cancersurface-functionalized liposomesT7 peptideorthotopic lung cancer modelpulmonary deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 2879-2902 (2019) |
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Quercetin lung cancer surface-functionalized liposomes T7 peptide orthotopic lung cancer model pulmonary delivery Medicine (General) R5-920 |
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Quercetin lung cancer surface-functionalized liposomes T7 peptide orthotopic lung cancer model pulmonary delivery Medicine (General) R5-920 Riaz MK Zhang X Wong KH Chen H Liu Q Chen X Zhang G Lu A Yang Z Pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy |
| description |
Muhammad Kashif Riaz,1 Xue Zhang,1 Ka Hong Wong,1 Huoji Chen,2 Qiang Liu,2 Xiaoyu Chen,1 Ge Zhang,1 Aiping Lu,1,3 Zhijun Yang1,31School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Changshu Research Institute, Hong Kong Baptist University, Changshu Economic and Technological Development (CETD) Zone, Changshu, Jiangsu Province, People’s Republic of ChinaPurpose: Lung cancer has a high incidence rate worldwide with a 5-year survival rate of 18%, and is the leading cause of cancer-related deaths. The aim of this study is to augment therapeutic efficacy of quercetin (QR) for lung cancer therapy by targeting transferrin receptors, which are overexpressed and confined to tumor cells.Methods: In this study, T7 surface-functionalized liposomes loaded with QR (T7-QR-lip) having different T7 peptide densities (0.5%, 1% and 2%) were prepared by the film hydration method. T7 surface-functionalized liposomes were characterized and evaluated in terms of in vitro cytotoxicity and cellular uptake, 3D tumor spheroid penetration and inhibition capabilities, in vivo biodistribution and therapeutic efficacy in mice with orthotopic lung-tumor implantation by fluorescent and bioluminescent imaging via pulmonary administration.Results: In vitro, 2% T7-QR-lip exhibited significantly augmented cytotoxicity (∼3-fold), higher apoptosis induction and S-phase cell-cycle arrest. A prominent peak right-shift and enhanced mean fluorescence intensity was observed in A549 cells treated with T7 Coumarin-6 liposomes (T7-Cou6-lip), confirming the target specificity of T7 targeted liposomes; while, after treatment with T7-QR-lip and non-targeted QR-lip, no significant difference was observed in cellular uptake and in vitro cytotoxicity studies in MRC-5 (normal lung fibroblast) cells. T7-Cou6-lip showed higher fluorescence intensity in A549 cells and a significantly deeper penetration depth of 120 μm in the core of the tumor spheroids and T7-QR-lip produced significantly higher tumor-spheroid growth inhibition. The in vivo biodistribution study via pulmonary delivery of T7 1,1’-dioctadecyltetramethyl-indotricarbocyanine iodide liposomes demonstrated liposome accumulation in the lungs and sustained-release behavior up to 96 h. Further, T7-QR-lip significantly enhanced the anticancer activity of QR and lifespan of mice (p<0.01, compared with saline) in orthotopic lung tumor-bearing mice via pulmonary administration.Conclusion: T7 surface-functionalized liposomes provide a potential drug delivery system for a range of anticancer drugs to enhance their therapeutic efficacy by localized (pulmonary) administration and targeted delivery.Keywords: Quercetin, lung cancer, surface-functionalized liposomes, T7 peptide, orthotopic lung cancer model, pulmonary delivery |
| format |
article |
| author |
Riaz MK Zhang X Wong KH Chen H Liu Q Chen X Zhang G Lu A Yang Z |
| author_facet |
Riaz MK Zhang X Wong KH Chen H Liu Q Chen X Zhang G Lu A Yang Z |
| author_sort |
Riaz MK |
| title |
Pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy |
| title_short |
Pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy |
| title_full |
Pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy |
| title_fullStr |
Pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy |
| title_full_unstemmed |
Pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy |
| title_sort |
pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/e864699d64274dc7b29d062d30a59a64 |
| work_keys_str_mv |
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