Mitochondria and Nucleus Dual Delivery System To Overcome DOX Resistance.
Doxorubicin (DOX) is a broad-spectrum chemotherapy drug to treat tumors. However, severe side effects and development of DOX resistance hinder its clinical application. In order to overcome DOX resistance, DOX/TPP-DOX@Pasp-hyd-PEG-FA micelles were prepared by using newly synthesized comb-like amphiphilic material Pasp-hyd-PEG-FA. Drug released in vitro from micelles showed a pH-dependent manner. DOX/TPP-DOX@Pasp-hyd-PEG-FA induced more apoptosis in KB cell and MCF-7/ADR cell than DOX@Pasp-hyd-PEG-FA. Confocal laser scanning microscopy experiment indicated that DOX/TPP-DOX@Pasp-hyd-PEG-FA delivered TPP-DOX and DOX to the nucleus and mitochondria of the tumor cell simultaneously. Thus, DOX/TPP-DOX@Pasp-hyd-PEG-FA could significantly damage the mitochondrial membrane potential. DOX/TPP-DOX@Pasp-hyd-PEG-FA markedly shrinked the tumor volume in tumor-bearing nude mice grafted with MCF-7/ADR cell as compared with the same dose of free DOX. DOX was mainly accumulated in tumor tissue after DOX/TPP-DOX@Pasp-hyd-PEG-FA was injected to tumor-bearing nude mice by tail vein. After free DOX was injected to tumor-bearing nude mice by tail vein, DOX widely distributed through the whole body. Therefore, mitochondria and nucleus dual delivery system has potential in overcoming DOX resistance.
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
Han
H
Cui
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
Meng-Lei
ML
Huan
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
Wei-Liang
WL
Ye
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
Dao-Zhou
DZ
Liu
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
Zeng-Hui
ZH
Teng
Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University , Xi'an, 710032, China.
Qi-Bing
QB
Mei
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.|Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University , Xi'an, 710032, China.
Si-Yuan
0000-0001-6092-4406
SY
Zhou
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007624:KB Cells; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry
D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005492:Folic Acid
(3-carboxypropyl)triphenylphosphonium; doxorubicin; mitochondria; pH-sensitive micelle