A self-activating nanovesicle with oxygen-depleting capability for efficient hypoxia-responsive chemo-thermo cancer therapy

Shi-Xiong Chen; Fengfeng Xue; Yichen Kuang; Siyu Chen; Danli Sheng; Hangrong Chen

doi:10.1016/j.biomaterials.2020.120533

A self-activating nanovesicle with oxygen-depleting capability for efficient hypoxia-responsive chemo-thermo cancer therapy

Biomaterials. 2021 Feb:269:120533. doi: 10.1016/j.biomaterials.2020.120533. Epub 2020 Nov 18.

Authors

Shi-Xiong Chen¹, Fengfeng Xue², Yichen Kuang¹, Siyu Chen³, Danli Sheng⁴, Hangrong Chen⁵

Affiliations

¹ State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, PR China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
² State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, PR China. Electronic address: xuefengfeng@mail.sic.ac.cn.
³ Department of Medical Imaging, The Third Affiliated Hospital, Orthopedic Hospital of Guangdong Province, Southern Medical University, Guangdong, 510000, PR China.
⁴ Department of Ultrasound, Fudan University, Shanghai Cancer Center, Shanghai, 200032, PR China.
⁵ State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, PR China; School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, PR China. Electronic address: hrchen@mail.sic.ac.cn.

PMID: 33228991
DOI: 10.1016/j.biomaterials.2020.120533

Abstract

Hypoxia-activated prodrugs (HAPs) promise to mitigate side effects of conventional chemotherapy and to enable precise medication treatment. One challenge facing HAPs-based chemotherapy is prodrug failure in normoxic tumor region. However, current strategies to enhance tumor hypoxia rely on delivery of oxygen-consuming agents and external stimulation, which can impede the optimal application of HAPs. Herein, a novel self-activating nanovesicle, TH-302@BR-Chitosan NPs, is constructed by assembling bilirubin-chitosan conjugate (named as BR-Chitosan) with a HAP, TH-302. It is interesting to find that the BR-Chitosan shows the inherent oxygen-depleting performance, especially in the presence of over expressed H₂O₂ in tumor area, during which the BR-Chitosan can facily transform into biliverdin-chitosan (BV-Chitosan) and subsequently result in the disassembly of nanovesicles to release and activate the prodrug. Thus, this in situ strengthening hypoxia level of tumor can greatly promote the chemotherapy efficacy of HAPs. Moreover, as the oxidation derivatives of BR-Chitosan, BV-Chitosan exhibits intense absorbance at the range from long wavelength of visible region to near-infrared region, which can be acted as an effective photothermal agent for photothermal therapy (PTT). This biodegradable and self-activating nanovesicle with concise formulation demonstrates greatly enhanced synergistic therapeutic outcome in the activatable chemo-thermo combined therapy, showing much promising in future clinical transformation.

Keywords: Activatable thermotherapy; Endogenous compound; Hypoxia-based chemotherapy; Oxygen-depleting capability; Self-activating nanovesicle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Humans
Hydrogen Peroxide
Hypoxia
Nanoparticles*
Neoplasms* / drug therapy
Oxygen
Prodrugs*

Substances

Prodrugs
Hydrogen Peroxide
Oxygen