pH-sensitive charge-conversional and NIR responsive bubble-generating liposomal system for synergetic thermo-chemotherapy

Ming-Mao Chen; Fei-Fei Song; Mei Feng; Yan Liu; Yuan-Yuan Liu; Jia Tian; Feng Lv; Qi-Qing Zhang

doi:10.1016/j.colsurfb.2018.04.001

pH-sensitive charge-conversional and NIR responsive bubble-generating liposomal system for synergetic thermo-chemotherapy

Colloids Surf B Biointerfaces. 2018 Jul 1:167:104-114. doi: 10.1016/j.colsurfb.2018.04.001. Epub 2018 Apr 3.

Authors

Ming-Mao Chen¹, Fei-Fei Song¹, Mei Feng², Yan Liu³, Yuan-Yuan Liu¹, Jia Tian¹, Feng Lv⁴, Qi-Qing Zhang⁵

Affiliations

¹ Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou, 350002, China.
² Department of Gynecology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China. Electronic address: conan12221@sina.com.
³ State Key Lab of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China.
⁴ Key Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. Electronic address: lvfeng2002@163.com.
⁵ Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou, 350002, China; Key Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. Electronic address: zhangqiq@126.com.

PMID: 29631221
DOI: 10.1016/j.colsurfb.2018.04.001

Abstract

A charge-conversional and NIR responsive rapid release liposomal system (PSD/DOX/Cypate-BTSL) was developed to enhance therapeutic efficacy of cancer therapy. The cationic liposomes containing Cypate, doxorubicin (DOX) and NH₄HCO₃ were shielded by pH-sensitive poly(methacryloyl sulfadimethoxine) (PSD) through electrostatic interaction at pH 7.4. At the tumor site (pH 6.5), PSD was deshielded and the liposomes displayed pH-sensitive charge reversal capability. The DOX released from PSD/DOX/Cypate-BTSL with irradiation was markedly higher than the other groups, indicating NIR irradiation and NH₄HCO₃ had a significant effect on the drug release. After irradiation, the hyperthermia induced by Cypate could produce CO₂ bubbles quickly on account of the decomposition of NH₄HCO₃, achieving the rapid drug release. In 4T1 cells, PSD/DOX/Cypate-BTSL improved cellular uptake and cytotoxicity with irradiation at pH 6.5. In vivo results implied that the liposomes with irradiation could efficiently enhance the tumor accumulation and antitumor efficacy, and reduce systemic side effects of DOX. In conclusion, PSD/DOX/Cypate-BTSL is a promising candidate as a carrier for synergistic effects of PTT and chemotherapy.

Keywords: Bubble-generating; Charge-conversion; NIR responsive; Thermo-chemotherapy; Thermosensive liposomes; pH-sensitive.

MeSH terms

Animals
Antibiotics, Antineoplastic / administration & dosage
Antibiotics, Antineoplastic / chemistry
Antibiotics, Antineoplastic / pharmacokinetics
Bicarbonates / chemistry
Cell Line, Tumor
Cell Survival / drug effects
Doxorubicin / administration & dosage
Doxorubicin / chemistry
Doxorubicin / pharmacokinetics
Drug Delivery Systems / methods
Drug Liberation
Drug Therapy / methods*
Hydrogen-Ion Concentration
Hyperthermia, Induced
Infrared Rays*
Liposomes / chemistry*
Mice, Nude
Neoplasms, Experimental / metabolism
Neoplasms, Experimental / pathology
Phototherapy / methods*

Substances

Antibiotics, Antineoplastic
Bicarbonates
Liposomes
ammonium bicarbonate
Doxorubicin