Folate-Functionalized Magnetic-Mesoporous Silica Nanoparticles for Drug/Gene Codelivery To Potentiate the Antitumor Efficacy

Abstract

An appropriate codelivery system for chemotherapeutic agents and nucleic acid drugs will provide a more efficacious approach for the treatment of cancer. Combining gene therapy with chemotherapeutics in a single delivery system is more effective than individual delivery systems carrying either gene or drug. In this work, we developed folate (FA) receptor targeted magnetic-mesoporous silica nanoparticles for the codelivery of VEGF shRNA and doxorubicin (DOX) (denoted as M-MSN(DOX)/PEI-FA/VEGF shRNA). Our data showed that M-MSN(DOX)/PEI-FA could strongly condense VEGF shRNA at weight ratios of 30:1, and possesses higher stability against DNase I digestion and sodium heparin. In vitro antitumor activity assays revealed that HeLa cell growth was significantly inhibited. The intracellular accumulation of DOX by confocal microscopy and fluorescence spectrophotometry showed that M-MSN(DOX)/PEI-FA were more easily taken up than nontargeted M-MSN(DOX). Quantitative PCR and ELISA data revealed that M-MSN/PEI-FA/VEGF shRNA induced a significant decrease in VEGF expression as compared to cells treated with either the control or other complexes. The invasion and migration phenotypes of the HUVECs were significantly decrease after coculture with MSN/PEI-FA/VEGF shRNA nanocomplexes-treated HeLa cells. The approach provides a potential strategy to treat cancer by a singular nanoparticle delivery system.

DOX-loaded pH-sensitive mesoporous silica nanoparticles coated with PDA and PEG induce pro-death autophagy in breast cancer

“…In addition, as a result of the slightly negative charge of MSNs-DOX@PDA-PEG, the overall clearance by the reticuloendothelial system (RES) such as liver was found to be reduced. 24,25 These data suggested that MSNs-DOX could be successfully synthesized and modied by introduction of PDA and PEG lms.…”

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

“…Silanol groups present on the surface of MSNs can be functionalized with various ligands, which could be one way of controlling nanoparticle (NP) biodistribution and the design of specific targeted delivery systems (Bouchoucha et al 2016;Li et al 2016). MSNs have been widely studied for their capability to load and release various drugs (Vallet-Reg ı, Balas, and Arcos 2007; Deodhar, Adams, and Trewyn 2017).…”

Co-delivery of doxorubicin and shRNA of Beclin1 by folate receptor targeted pullulan-based multifunctional nanomicelles for combinational cancer therapy

“…Critical micellar concentration (CMC) of FPDP was determined using pyrene as the probe by uorescence spectroscopy (LS55, PerkinElmer). 20,[37][38][39] The particle size and zeta potential of FPDP, FPDP/DOX, FPDP/shBeclin1 and FPDP/DOX/shBeclin1 micelles were measured by dynamic light scattering (DLS) using Malvern Zetasizer NanoZS90 (Malvern instruments, UK). The morphology of micelles was observed by transmission electron microscopy (TEM, Tecnai G2 Spirit 120 kV).…”

“…In this contribution, a nanocarrier-based delivery system offers a platform for the co-delivery of siRNA (shRNA) and anticancer chemotherapeutics simultaneously to the same tumor cells. 16 In recent years, enormous efforts have been put into the development of novel siRNA (shRNA) and DOX co-delivery systems with enhanced bioavailability, low toxicity and prolonged circulation time, such as polymers, 11,17 liposomes, 18 dendrimers, 19 mesoporous silica nanoparticles 13,20,21 and quantum-dot (QD)-based nanoparticles. 22 Among those systems, the amphiphilic cationic copolymers are widely used due to their excellent biocompatibility, desirable biodegradability, and unique self-assembling property.…”