Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 29, Issue 19, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201900004
Keywords
activated targeting; combinatorial therapy; controlled release; hybrid nanoparticles; supramolecular assembling
Categories
Funding
- National Natural Science Fund for Distinguished Young Scholar [NSFC31525009]
- National Natural Science Funds [NSFC31771096, NSFC31871008, NSFC31500809]
- Sichuan Innovative Research Team Program for Young Scientists [2016TD0004]
- 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University
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Nanomedicine constructed by therapeutics has unique and irreplaceable advantages in biomedical applications, especially in drug delivery for cancer therapy. The strategy, however, used to construct the therapeutics-based nanomedicines with tumor microenvironmental factor responsiveness is still sophisticated. In this study, an easy-operating procedure is used to construct a therapeutics-based nanosystem with active tumor-targeting, enhanced penetration, and stimuli-responsive drug release behavior as well as programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) blockading mediated immunomodulation to enhance tumor immunotherapy. The matrix metalloproteinase-2 responsive peptide with the existence of Lyp-1 sequence contributes to the success of active tumor-targeting and the enhancement of the penetration of the nanoparticles in tumor tissue. The obtained nanosystem strikingly inhibits the primary tumor growth in the first 24 h (more than 97.5% of tumor cells are inhibited), and total inhibition can be achieved with the combination of photothermal therapy. IR820, which is served as the carrier for the therapeutics, is used as a photosensitizer for photothermal therapy. The progress and aggression of distal tumor has further been alleviated by a d-peptide which is an antagonist for PD-1/PD-L1 blockage. Therefore, a therapeutics-constructed multifunctional nanosystem is provided to realize a combinational therapeutic strategy to enhance the therapeutic outcome.
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