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Mesoporous silica nanoparticles (MSNs)-based organic/inorganic hybrid nanocarriers loading 5-Fluorouracil for the treatment of colon cancer with improved anticancer efficacy.
Colloids and Surfaces. B, Biointerfaces 2017 November 2
Novel methods to improve the anticancer performance of 5-fluorouracil (5-FU) is quite necessary for clinical medicines. In the present work, we fabricated a novel type of mesoporous silica nanoparticles (MSNs)-based inorganic/organic hybrid nanoparticles covalently attached with poly(oligo(ethylene glycol) monomethyl ether methacrylate) (POEGMA) for improved stabilization and targeting peptide (RGD) for targeted delivery with the aim of improving the anticancer performance of 5-FU. Atom transfer radical polymerization (ATRP) initiator functionalized MSN (MSN-Br) was synthesized at first, which was followed by surface-initiated ATRP of water soluble OEGMA and carboxyl-containing monomer (2-succinyloxyethyl methacrylate, SEMA). Functionalization of RGD onto the hydrophilic P(OEGMA-co-SEMA) chains afforded the final hybrid nanoparticle, MSN-P(OEGMA-co-RGD). 5-FU can be effectively loaded into the meso-pores of MSN-P(OEGMA-co-RGD) (5-FU@MSN-RGD) with drug content ∼7.5wt%. And the dynamic diameter (Dh ) and zeta potential (ζ) of 5-FU@MSN-RGD were determined to be 199.3±5.4nm and -8.7±0.5mV, respectively. It was demonstrated that MSN-P(OEGMA-co-RGD) exhibited improved internalization into colon cancer cells and enhanced accumulation in tumor tissues. In addition, compared with free 5-FU, 5-FU@MSN-RGD showed enhanced anticancer efficacy both in vitro and in vivo, implying promising clinical applications.
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