期刊
BIOMACROMOLECULES
卷 18, 期 8, 页码 2571-2582出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.7b00693
关键词
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资金
- National Natural Science Foundation of China (NNSFC) [51690150, 51690154, 21674103, 51673179]
- International S&T Cooperation Program of China (ISTCP) of MOST [2016YFE0129700]
- Fundamental Research Funds for the Central Universities [WK2060200023]
The use of intracellular reductive microenvironment to control the release of therapeutic payloads has emerged as a popular approach to design and fabricate intelligent nanocarriers. However, these reduction-responsive nanocarriers are generally trapped within endolysosomes after internalization and are subjected to unwanted disintegration, remarkably compromising the therapeutic performance. Herein, amphiphilic polyprodrugs of poly(N,N-dimethylacrylamide-co-EoS)-b-PCPTM were synthesized via sequential reversible addition fragmentation chain transfer (RAFT) polymerization, where EoS and CPTM are Eosin Y- and camptothecin (CPT)-based monomers, respectively. An oil-in-water (O/W) emulsion method was applied to self-assemble the amphiphilic polyprodrugs into hybrid vesicles in the presence of hydrophobic oleic acid (OA)-stabilized upconversion nanoparticles (UCNPs, NaYF4:Yb/Er), rendering it possible to activate the EoS photosensitizer under a near infrared (NIR) laser irradiation with the generation of singlet oxygen (O-1(2)) through the energy transfer between UCNPs and EoS moieties. Notably, the in situ generated singlet oxygen (O-1(2)) can not only exert its photodynamic therapy (PDT) effect but also disrupt the membranes of endolysosomes and thus facilitate the endosomal escape of internalized nanocarriers (i.e., photochemical internalization (PCI)). Cell experiments revealed that the hybrid vesicles could be facilely taken up by endocytosis. Although the internalized hybrid vesicles, were initially trapped within endolysosomes, a remarkable endosomal escape into the cytoplasm was observed under 980 nm laser irradiation as a result of the PCI effect of O-1(2). The escaped hybrid vesicles subsequently underwent GSH-triggered CPT release in the cytosol, thereby activating the chemotherapy process. The integration of PDT module into the design of reduction-responsive nanocarriers provides a feasible approach to enhance the therapeutic performance.
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