Platinum-based polypyrrole is used in oxygen-enhanced photodynamic therapy
10.16438/j.0513-4870.2024-0245
- VernacularTitle:键合光敏剂的铂基聚吡咯用于氧气增强的光动力治疗
- Author:
Yue ZHANG
1
;
Han-yue LI
2
;
Wei-jian ZENG
3
;
Lin MEI
2
;
Da-quan CHEN
1
Author Information
1. Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China
2. State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
3. College of Science and Technology, Ningbo University, Ningbo 315212, China
- Publication Type:Research Article
- Keywords:
polypyrrole;
nano-drug;
photodynamic therapy;
tumor hypoxia;
oxidative damage
- From:
Acta Pharmaceutica Sinica
2024;59(7):2153-2160
- CountryChina
- Language:Chinese
-
Abstract:
Photodynamic therapy is an emerging cancer therapy with clinical prospects, which plays a specific role in the tumor site and causes less harm to the human body. However, the toxicity of small molecules of hydrophobic photosensitizer, the tumor hypoxia microenvironment, and the biodegradability of nano-carrier systems affect its antitumor efficacy and metabolic clearance in vivo. In this paper, hexachloroplatinic acid was used as a novel oxidizing agent to initiate oxidative polymerization of pyrrole/amino pyrrole to achieve the amino functionalization; further reduced platinum acid anion in the nanostructures into platinum nanoclusters by sodium borohydride as a reducing agent to fabricate platinum nanocluster-doped polypyrrole nanoparticles (PtPPy); and finally, this functional nanoparticles delivering meso-tetra (4-carboxyphenyl) porphine (TCPP) were obtained by amide-bonded coupling of photosensitizers TCPP drug (PtPPy@T). The nanomedicine had a spherical structure, uniform morphology, a particle size of 91.93 ± 13.45 nm, and a zeta potential of -18.39 ± 1.4 mV. Experiments demonstrated that PtPPy@T could react with hydrogen peroxide overexpressed in the tumor to generate a large amount of oxygen, which could relieve the tumor hypoxia microenvironment, and at the same time, provided a sufficient substrate for the subsequent PDT; using 658 nm laser irradiation, the photodynamic effect of PtPPy@T was activated, which catalyzed the conversion of oxygen to singlet oxygen, thus triggering oxidative damage and inducing apoptosis in tumor cells; experimental studies showed that the PtPPy@T nanomedicine had a better tumor inhibitory effect in vivo and in vitro. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Radiological Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College (IRM/2-IACUC-2312-006).
