pH-Sensitive and Charge-Reversal Polymeric Nanoplatform Enhanced Photothermal/Photodynamic Synergistic Therapy for Breast Cancer

Wenyan Wang; Zimu Li; Xiaozhong Nie; Wenfeng Zeng; Yi Zhang; Yimin Deng; Hongzhong Chen; Xiaowei Zeng; Hualin Ma; Yi Zheng; Nansha Gao

doi:10.3389/fbioe.2022.836468

pH-Sensitive and Charge-Reversal Polymeric Nanoplatform Enhanced Photothermal/Photodynamic Synergistic Therapy for Breast Cancer

Front Bioeng Biotechnol. 2022 Feb 18:10:836468. doi: 10.3389/fbioe.2022.836468. eCollection 2022.

Authors

Wenyan Wang¹, Zimu Li¹, Xiaozhong Nie², Wenfeng Zeng¹, Yi Zhang¹, Yimin Deng¹, Hongzhong Chen¹, Xiaowei Zeng¹, Hualin Ma³, Yi Zheng⁴, Nansha Gao¹

Affiliations

¹ Institute of Pharmaceutics, School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.
² School of Food and Drug, Shenzhen Polytechnic, Shenzhen, China.
³ Shenzhen Key Laboratory of Kindey Diseases, Department of Nephrology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
⁴ Central Laboratory, University of Chinese Academy of Sciences-Shenzhen Hospital, Shenzhen, China.

Abstract

As reported, breast cancer is one of the most common malignancies in women and has overtaken lung cancer as the most commonly diagnosed cancer worldwide by 2020. Currently, phototherapy is a promising anti-tumor therapy due to its fewer side effects, less invasiveness, and lower cost. However, its application in cancer therapeutics is limited by the incomplete therapeutic effect caused by low drug penetration and monotherapy. Herein, we built a charge-reversal nanoplatform (Ce6-PLGA@PDA-PAH-DMMA NPs), including polydopamine (PDA) and chlorin e6 (Ce6) for enhancing photothermal/photodynamic synergistic therapy. The PAH-DMMA charge-reversal layer enabled Ce6-PLGA@PDA-PAH-DMMA NPs to have long blood circulation at the normal physiological environment and to successfully realize charge reversal under the weakly acidic tumor microenvironment, improving cellular uptake. Besides, in vitro tests demonstrated that Ce6-PLGA@PDA-PAH-DMMA NPs had high photothermal conversion and greater anti-tumor activity than no charge-reversal nanoparticles, which overcame the limited tumor therapeutic efficacy of PTT or photodynamic therapy alone. Overall, the design of pH-responsive and charge-reversal nanoparticles (Ce6-PLGA@PDA-PAH-DMMA NPs) provided a promising approach for synergistic PTT/PDT therapy against breast cancer.

Keywords: cancer nanotechnology; charge-reversal; pH-sensitive; photodynamic therapy; photothermal therapy.