期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 13, 期 5, 页码 1797-1808出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2017.02.010
关键词
Poly (propargyl L-glutamate); Drug delivery; Nanocarriers; Block copolymers
资金
- NIH
- Center for Cancer Nanotechnology Excellence (CCNE) [P30 CA14051, 5 U54 CA151884-02]
- Novartis Institutes for Biomedical Research, Inc.
- Misrock Foundation
- Koch Institute for Integrative Cancer Research at MIT
- Misrock Foundation Fellowship
- NSF
- NSERC
A ligand decorated, synthetic polypeptide block copolymer platform with environment-responsive capabilities was designed. We evaluated the potential of this system to function as a polymersome for targeted-delivery of a systemic chemotherapy to tumors. Our system employed click chemistry to provide a pH-responsive polypeptide block that drives nanoparticle assembly, and a ligand (folic acid) conjugated PEG block that targets folate-receptor over-expressing cancer cells. These nanocarriers were found to encapsulate a high loading of conventional chemotherapeutics (e.g. doxorubicin at physiological pH) and release the active therapeutic at lysosomal pH upon cellular uptake. The presence of folic acid on the nanoparticle surface facilitated their active accumulation in folate-receptor-overexpressing cancer cells (KB), compared to untargeted carriers. Folate-targeted nanoparticles loaded with doxorubicin also showed enhanced tumor accumulation in folate-receptor positive KB xenografts, resulting in the suppression of tumor growth in an in vivo hind flank xenograft mouse model. (C) 2017 Published by Elsevier Inc.
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