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...

Full description

Bibliographic Details
Main Authors: Aiyun Liu, Huaisong Wang, Xiaoshuang Hou, Yu Ma, Gongjun Yang, Yanglong Hou, Ya Ding
Format: Article
Language:English
Published: Elsevier 2020-04-01
Series:Acta Pharmaceutica Sinica B
Online Access:http://www.sciencedirect.com/science/article/pii/S2211383519307853
id doaj-0767f0fbc5524609b5c5b51e1a158f83
record_format Article
spelling 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
work_keys_str_mv AT aiyunliu combinatoryantitumortherapybycascadetargetingofasingledrug
AT huaisongwang combinatoryantitumortherapybycascadetargetingofasingledrug
AT xiaoshuanghou combinatoryantitumortherapybycascadetargetingofasingledrug
AT yuma combinatoryantitumortherapybycascadetargetingofasingledrug
AT gongjunyang combinatoryantitumortherapybycascadetargetingofasingledrug
AT yanglonghou combinatoryantitumortherapybycascadetargetingofasingledrug
AT yading combinatoryantitumortherapybycascadetargetingofasingledrug
_version_ 1724877416163180544