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Abstract:
Poly gamma-glutamic acid (gamma-PGA) is attractive due to its desirable biological properties such as nontoxicity, excellent biocompatibility, and minimal immunogenicity. Additionally, gamma-PGA could be recognized by gamma-glutamyl transpeptidase, which is regarded as a potential biomarker for many tumors. In this study, we have developed a new biodegradable, reduction sensitive, and tumor-specific gene nano-delivery platform consisting of a cationic carrier (SSBPEI) for siRNA condensation, mPEG shell for nanoparticle stabilization, and gamma-PGA for accelerated cellular uptake. Disulfide bonds (-SS-) could be reduced specifically in the tumor environment, which is full of reductants such as glutathione reductase. Conjugating polyethylene glycol (PEG) to the gamma-PGA led to the formation of mPEG-g-gamma-PGA, with a decreased positive charge on the surface of SSBPEI@siRNA and substantially higher stability in an aqueous medium. As a result, mPEG-g-gamma-PGA/SSBPEI@siRNA nanoparticles could protect siRNAs from RNase A degradation and release siRNAs in a reduction sensitive way. The multifunctional delivery system was shown to silence the Survivin gene and further promote chemotherapeutic drug-induced apoptosis in the A549 NSCLC cell line efficiently, thereby representing a novel promising platform for the delivery of siRNAs.
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COLLOIDS AND SURFACES B-BIOINTERFACES
ISSN: 0927-7765
Year: 2020
Volume: 193
5 . 2 6 8
JCR@2020
5 . 4 0 0
JCR@2023
ESI Discipline: BIOLOGY & BIOCHEMISTRY;
ESI HC Threshold:156
JCR Journal Grade:1
CAS Journal Grade:2
Cited Count:
WoS CC Cited Count: 10
SCOPUS Cited Count: 10
ESI Highly Cited Papers on the List: 0 Unfold All
WanFang Cited Count:
Chinese Cited Count:
30 Days PV: 0
Affiliated Colleges: