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  3. PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion

PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion

  • Int J Biol Macromol. 2024 May;266(Pt 2):131359. doi: 10.1016/j.ijbiomac.2024.131359.
Yu-Hsin Chen 1,  I-Ju Liu 1,  Tzu-Chen Lin 1,  Min-Chen Tsai 1,  Shang-Hsiu Hu 2,  Tsai-Ching Hsu 3,  Yi-Ting Wu 4,  Bor-Show Tzang 5,  Wen-Hsuan Chiang 6
Affiliations

Affiliations

  • 1 Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan.
  • 2 Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
  • 3 Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
  • 4 Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
  • 5 Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan; Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan. Electronic address: bstzang@csmu.edu.tw.
  • 6 Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: whchiang@dragon.nchu.edu.tw.
PMID: 38580018 DOI: 10.1016/j.ijbiomac.2024.131359
Abstract

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a promising strategy for Cancer treatment. However, the poor photostability and photothermal conversion efficiency (PCE) of organic small-molecule photosensitizers, and the intracellular glutathione (GSH)-mediated singlet oxygen scavenging largely decline the antitumor efficacy of PTT and PDT. Herein, a versatile nanophotosensitizer (NPS) system is developed by ingenious incorporation of indocyanine green (ICG) into the PEGylated chitosan (PEG-CS)-coated polydopamine (PDA) nanoparticles via multiple π-π stacking, hydrophobic and electrostatic interactions. The PEG-CS-covered NPS showed prominent colloidal and photothermal stability as well as high PCE (CA 62.8 %). Meanwhile, the Michael addition between NPS and GSH can consume GSH, thus reducing the GSH-induced singlet oxygen scavenging. After being internalized by CT26 cells, the NPS under near-infrared laser irradiation produced massive singlet oxygen with the aid of thermo-enhanced intracellular GSH depletion to elicit mitochondrial damage and lipid peroxide formation, thus leading to Ferroptosis and Apoptosis. Importantly, the combined PTT and PDT delivered by NPS effectively inhibited CT26 tumor growth in vivo by light-activated intense hyperthermia and redox homeostasis disturbance. Overall, this work presents a new tactic of boosting antitumor potency of ICG-mediated phototherapy by PEG-CS-covered NPS.

Keywords

Nanophotosensitizer; PEGylated chitosan; Photothermal-photodynamic therapy.

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