Cholesterol-Modified Dendrimers for Constructing a Tumor Microenvironment-Responsive Drug Delivery System

被引:25
|
作者
Xu, Ke-Fei [1 ]
Jia, Hao-Ran [1 ]
Zhu, Ya-Xuan [1 ]
Liu, Xiaoyang [1 ]
Gao, Ge [1 ]
Li, Yan-Hong [1 ]
Wu, Fu-Gen [1 ]
机构
[1] Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, 2 Sipailou Rd, Nanjing 210096, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
dendrimer; cholesterol-dependent endocytosis; pH/H2O2-responsive; nanozyme; enhanced PDT; ENCAPSULATED METAL NANOPARTICLES; PHOTODYNAMIC THERAPY; MNO2; NANOPARTICLES; ORGANIC FRAMEWORKS; HYPOXIA; EFFICIENT; CANCER; PH; CHEMOTHERAPY; GLUTATHIONE;
D O I
10.1021/acsbiomaterials.9b01386
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
Poly(amidoamine) (PAMAM) dendrimers are widely used as templates for synthesizing small nanoparticles. Herein, the surfaces of amine-terminated generation 4 (G4-NH2) poly(amidoamine) (PAMAM) dendrimers are modified with poly(ethylene glycol)-cholesterol to form self-assembled nanoparticles (termed DPC NPs). It is found that the cellular uptake of DPC NPs increases in a cholesterol-content-dependent manner. Benefiting from the hydrophobic cores of dendrimers, the DPC NPs are developed as drug carriers to encapsulate the photosensitizer chlorin e6 (Ce6) to obtain DPCC NPs for photodynamic therapy (PDT). To improve the PDT efficacy of the DPCC NPs in hypoxic tumor tissues, MnO2 was synthesized in DPCC NPs in situ to obtain Ce6/MnO2@DPC NPs (termed DPCCM NPs) based on the strong coordination between dendrimer and Mn2+. The as-designed DPCCM NPs behave like nanozymes, which can catalyze H2O2 to produce O-2 and achieve enhanced PDT effect upon 670 nm laser irradiation. The in vivo imaging experiments for cyanine7 (a near-infrared fluorescent dye)-conjugated DPCCM NPs reveal the excellent tumor accumulation performance of the nanozyme in tumor-bearing mice after intravenous administration. Finally, we have demonstrated the satisfactory in vivo antitumor therapeutic outcome and the good biosafety of the nanozyme. This work provides a new strategy for increasing the cellular uptake of drugs and proposes a method of synthesizing smart nanozymes based on dendrimers.
引用
收藏
页码:6072 / 6081
页数:19
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