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Redox Stimuli Delivery Vehicle Based on Transferrin-Capped MSNPs for Targeted Drug Delivery in Cancer Therapy
Version 2 2019-04-02, 18:42
Version 1 2019-03-22, 17:34
journal contribution
posted on 2019-03-08, 00:00 authored by Parthiban Venkatesan, Natesan Thirumalaivasan, Hsiu-Ping Yu, Ping-Shan Lai, Shu-Pao WuCancer
has become one of the major diseases of human health around
the world. Conventional antitumor drugs cannot specifically target
cancers and result in serious side effects. To achieve better therapy,
innovative functional drug delivery platforms that will aid specific
targeting for cancer cells need to be developed. In this study, transferrin
(Tf), which can target cancer cells, is covalently anchored onto the
surface of MSNPs via disulfide linkage, which is used for glutathione-triggered
intracellular drug release in tumor cells. The successful functionalization
of redox-responsive MSNPs is confirmed by using BET/BJH, TEM, TGA,
NMR, and FT-IR (BET, Brunauer–Emmett–Teller; BJH, Barrett–Joyner–Halenda).
In addition, polyethylene glycol (PEG) is further grafted onto the
surface of MSNPs to improve the biocompatibility and stability under
physiological conditions for longer blood circulation. Our in vitro studies demonstrate that DOX-loaded MSNP–SS–Tf@PEG
can selectively be internalized into cancer cells via Tf/Tf receptor
interactions, and then, DOX is released in HT-29 and MCF-7 cells triggered
by high GSH concentration in tumor cells. Remarkably, in vivo studies demonstrate that DOX-loaded MSNP–SS–Tf@PEG
can significantly inhibit tumor growth with minimized side effects
through cell apoptosis determined by TUNEL assay, whereas MSNP–SS–Tf@PEG
revealed no significant inhibition. In conclusion, DOX–MSNP–SS–Tf@PEG
with active targeting moieties and a redox-responsive strategy has
been demonstrated as a great effective drug carrier for tumor therapy in vitro and in vivo.