Doxorubicin-Loaded Photosensitizer-Core pH-Responsive Copolymer Nanocarriers for Combining Photodynamic Therapy and Chemotherapy

被引:25
作者
Zhang, Xiaohan [1 ,2 ]
Li, Qiu [1 ,3 ]
Sun, Xiaodong [1 ,2 ]
Zhang, Baolei [1 ,2 ]
Kang, Hongxiang [1 ]
Zhang, Fuli [2 ]
Jin, Yiguang [1 ,2 ]
机构
[1] Beijing Inst Radiat Med, Dept Pharmaceut Sci, 27 Taiping Rd, Beijing 100850, Peoples R China
[2] Henan Univ, Pharmaceut Coll, Inst Pharm, Kaifeng 475004, Peoples R China
[3] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Ave Padre Tomas Pereira, Taipa, Macao, Peoples R China
基金
中国国家自然科学基金;
关键词
doxorubicin; pH-responsive; photodynamic therapy; phthalocyanine; photosensitizer; tumor targeting; CANCER-THERAPY; CHITOSAN NANOPARTICLES; DELIVERY; PHTHALOCYANINE; PSORIASIS; NANOMATERIALS; CONJUGATE; EFFICACY;
D O I
10.1021/acsbiomaterials.6b00762
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Photodynamic therapy (PDT) is an emerging method for the treatment of cancer. Combination of PDT and chemotherapy is a hot topic though the two therapies could not simultaneously exert their perfect effect in vivo. Here we report a doxorubicin-loaded photosensitizer-core pH-responsive copolymer nanocarrier with high tumor targeting and anticancer effects due to integration of PDT with chemotherapy. The pH-responsive photosensitizer-core four-armed star-shaped copolymer, [methoxy-poly(ethylene glycol)-poly(2-(N,N-diethylamino)ethyl methacrylate)-poly(epsilon-caprolactone)](4)-zinc beta-tetra-(4-carboxyl benzyloxyl)phthalocyanine (PDCZP), was prepared, which was a molecular spherical nanocarrier in aqueous media. The carriers changed from small at high pH to large at low pH (51, 105, and 342 nm at pH 7.4, 6.5, and 5.0, respectively) and the zeta potential gradually increased (7.15, 16.2, and 26.1 mV at the above pH, respectively). PDCZP had a longer emission wavelength (max. 677 nm) than the parent photosensitizer, favoring light penetration through biological tissues. The singlet oxygen (O-1(2)) quantum yield of PDCZP was 0.41. Doxorubicin (DOX) showed rapid release from PDCZP in the acidic media. More importantly, the drug-loaded nanocarriers showed the better in vitro and in vivo anticancer effects under lighting on MCF-7, SW480 cells and HepG2 cells and the murine hepatocellular carcinoma H-22 models than the other groups. PDCZP showed a high tumor targeting effect based on the enhanced permeation and retention effect and its small size. The photosensitizer-core nanocarrier is a promising photodynamic nanocarrier for integrating other therapies.
引用
收藏
页码:1008 / 1016
页数:9
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