Combinatory antitumor therapy by cascade targeting of a single drug
Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment. However, the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great challenge. In this work, a single model drug, paclitaxel (PTX), is used to realiz...
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doaj-0767f0fbc5524609b5c5b51e1a158f832020-11-25T02:19:14ZengElsevierActa Pharmaceutica Sinica B2211-38352020-04-01104667679Combinatory antitumor therapy by cascade targeting of a single drugAiyun Liu0Huaisong Wang1Xiaoshuang Hou2Yu Ma3Gongjun Yang4Yanglong Hou5Ya Ding6Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, ChinaBeijing Key Laboratory for Magnetoeletric Materials and Devices, Beijing Innovation Center for Engineering Science and Advanced Technology, Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China; Corresponding authors. Tel./fax: +86 25 83271326.Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China; Corresponding authors. Tel./fax: +86 25 83271326.Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment. However, the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great challenge. In this work, a single model drug, paclitaxel (PTX), is used to realize combination therapy and solve the problems mentioned above. Either PTX or its triphenylphosphine derivative (TPTX) is encapsulated in galactose-modified liposomes (GLips) to obtain GLips-P or GLips-TP, which are simply mixed in different ratios to finely control the proportion of PTX and TPTX. These mixed liposomes, GLips-P/TP, feature a cascade target delivery of PTX, from tissue to cell, and then to organelle. PTX plays a primary role to cause the cytotoxicity by microtubule bindings in cytoplasm, while TPTX is proved to increase the intracellular levels of caspase-3 and caspase-9 that cause apoptosis via a mitochondria-mediated pathway. Notably, GLips-P/TP 3:1 exhibited the significant drug synergy in both cytotoxicity assay of HepG2 cells and the treatment efficacy in Heps xenograft ICR mouse models. This work not only demonstrates the great promise of a cascade targeting delivery for precise tumor treatment, but also offers a novel platform to design combinatory therapy systems using a single drug. KEY WORDS: Combin chemotherapy, Single drug, Paclitaxel, Microtubules, Mitochondria, Cytotoxicityhttp://www.sciencedirect.com/science/article/pii/S2211383519307853 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aiyun Liu Huaisong Wang Xiaoshuang Hou Yu Ma Gongjun Yang Yanglong Hou Ya Ding |
spellingShingle |
Aiyun Liu Huaisong Wang Xiaoshuang Hou Yu Ma Gongjun Yang Yanglong Hou Ya Ding Combinatory antitumor therapy by cascade targeting of a single drug Acta Pharmaceutica Sinica B |
author_facet |
Aiyun Liu Huaisong Wang Xiaoshuang Hou Yu Ma Gongjun Yang Yanglong Hou Ya Ding |
author_sort |
Aiyun Liu |
title |
Combinatory antitumor therapy by cascade targeting of a single drug |
title_short |
Combinatory antitumor therapy by cascade targeting of a single drug |
title_full |
Combinatory antitumor therapy by cascade targeting of a single drug |
title_fullStr |
Combinatory antitumor therapy by cascade targeting of a single drug |
title_full_unstemmed |
Combinatory antitumor therapy by cascade targeting of a single drug |
title_sort |
combinatory antitumor therapy by cascade targeting of a single drug |
publisher |
Elsevier |
series |
Acta Pharmaceutica Sinica B |
issn |
2211-3835 |
publishDate |
2020-04-01 |
description |
Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment. However, the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great challenge. In this work, a single model drug, paclitaxel (PTX), is used to realize combination therapy and solve the problems mentioned above. Either PTX or its triphenylphosphine derivative (TPTX) is encapsulated in galactose-modified liposomes (GLips) to obtain GLips-P or GLips-TP, which are simply mixed in different ratios to finely control the proportion of PTX and TPTX. These mixed liposomes, GLips-P/TP, feature a cascade target delivery of PTX, from tissue to cell, and then to organelle. PTX plays a primary role to cause the cytotoxicity by microtubule bindings in cytoplasm, while TPTX is proved to increase the intracellular levels of caspase-3 and caspase-9 that cause apoptosis via a mitochondria-mediated pathway. Notably, GLips-P/TP 3:1 exhibited the significant drug synergy in both cytotoxicity assay of HepG2 cells and the treatment efficacy in Heps xenograft ICR mouse models. This work not only demonstrates the great promise of a cascade targeting delivery for precise tumor treatment, but also offers a novel platform to design combinatory therapy systems using a single drug. KEY WORDS: Combin chemotherapy, Single drug, Paclitaxel, Microtubules, Mitochondria, Cytotoxicity |
url |
http://www.sciencedirect.com/science/article/pii/S2211383519307853 |
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