Reduction-responsive worm-like nanoparticles for synergistic cancer chemo-photodynamic therapy

Hang Hu; Defeng Xu; Qingbo Xu; Yuxiang Tang; Jun Hong; Yu Hu; Jianhao Wang; Xinye Ni

doi:10.1016/j.mtbio.2023.100542

Reduction-responsive worm-like nanoparticles for synergistic cancer chemo-photodynamic therapy

Mater Today Bio. 2023 Jan 4:18:100542. doi: 10.1016/j.mtbio.2023.100542. eCollection 2023 Feb.

Authors

Hang Hu¹, Defeng Xu², Qingbo Xu³, Yuxiang Tang^{4

5}, Jun Hong², Yu Hu^{4

5}, Jianhao Wang², Xinye Ni¹

Affiliations

¹ Second People's Hospital of Changzhou, Nanjing Medical University, Changzhou, Jiangsu, China.
² School of Pharmacy, Changzhou University, Changzhou, Jiangsu, China.
³ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Interventional Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, China.
⁴ Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, China.

Abstract

Chemo-photodynamic therapy shows great potential for cancer treatment. However, the rational integration of chemotherapeutic agents and photosensitizers to construct an intelligent nanoplatform with synergistic therapeutic effect is still a great challenge. In this work, curcumin-loaded reduction-responsive prodrug nanoparticles of new indocyanine green (Cur@IR820-ss-PEG) were developed for synergistic cancer chemo-photodynamic therapy. Cur@IR820-ss-PEG exhibit high drug loading content and special worm-like morphology, contributing to their efficient cellular uptake. Due to the presence of the disulfide bond between IR820 and PEG, Cur@IR820-ss-PEG display reduction responsive drug release behaviors. The efficient cellular uptake and reduction triggered drug release of Cur@IR820-ss-PEG lead to their enhanced in vitro cytotoxicity against 4T1cells as compared to the mixture of IR820 and curcumin (IR820/Cur) under laser irradiation. Besides, Cur@IR820-ss-PEG exhibit prolonged blood half-life time, better tumor accumulation and retention, enhanced tumor hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) suppression effect as compared to IR820/Cur. In vivo antitumor activity study, Cur@IR820-ss-PEG effectively inhibit the tumor angiogenesis, which potentiates the PDT efficacy and leads to the best in vivo antitumor effect of Cur@IR820-ss-PEG. This work provides a novel and relatively simple strategy for synergistic cancer chemo-photodynamic therapy.

Keywords: Angiogenesis; Curcumin; New indocyanine green; Photodynamic therapy; Prodrug nanoparticles.