Title

Bubble-Generating Polymersomes Loaded with Both Indocyanine Green and Doxorubicin for Effective Chemotherapy Combined with Photothermal Therapy

Abstract

The combination of chemotherapy and photothermal therapy (PTT) via stimuli-responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo-photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000-PEG8000-PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure. Under acidic condition or laser irradiation, the ammonium bicarbonate (NH4HCO3) encapsulated in the bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would decompose to produce CO2 bubbles, resulting in destruction of vesicle structure and rapid drug release. In vitro drug release study confirmed that acidic environment and NIR laser irradiation could accelerate DOX release from the BG-DIPS. Cellular uptake study indicated that laser-induced hyperthermia highly enhanced endocytosis of BG-DIPS into 4T1-Luc cancer cells. In vitro cytotoxicity study demonstrated that BG-DIPS exhibited much higher cytotoxicity than free drugs under laser irradiation. In vivo biodistribution study indicated that BG-DIPS could accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. Furthermore, in vivo antitumor study showed that BG-DIPS with laser irradiation efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy.

Statement of Significance: The combination of chemotherapy and photothermal therapy via stimuli-responsive nanovesicles has great potential in tumor treatment. Herein, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug (DOX) and photosensitizing agent (ICG) for the synergistic chemo-photothermal tumor therapy. The results in vitro and in vivo demonstrated that bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would accelerate DOX release from the BG-DIPS and accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. BG-DIPS with laser irradiation could efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy.

Department(s)

Chemical and Biochemical Engineering

Comments

The authors are grateful for the financial support by National Natural Science Foundation of China (Nos. 81571793, 81671806, 81671694 and 31670948), CAMS Innovation Fund for Medical Sciences (Nos. 2017-I2M-3-020 and 2017-I2M-4-001), Tianjin Municipal Natural Science Foundation (Nos. 15JCZDJC38300 and 15JCQNJC46200) and Science and Technology Support Program of Tianjin (No. 14RCGFSY00146), Beijing Municipal Natural Science Foundation (No. 7172072), Program for Innovative Research Team in Peking Union Medical College, PUMC Youth Fund (No. 2017310031), Science Foundation for The Youth Teachers of Peking Union Medical College (grant number 2014zlgc0754), Scientific Research Foundation of the State Human Resource Ministry and the Education Ministry for Returned Chinese Scholars.

Keywords and Phrases

Bubble-generating; Chemo-photothermal therapy; Doxorubicin; Indocyanine green; Polymersomes

International Standard Serial Number (ISSN)

1742-7061; 1878-7568

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2018 Acta Materialia Inc, All rights reserved.

Publication Date

15 Jul 2018

PubMed ID

29793073

Share

 
COinS