Smart MSN-Drug-Delivery System for Tumor Cell Targeting and Tumor Microenvironment Release

Abstract

Tumor-targeted delivery and controlled release of antitumor drugs are promising strategies for increasing chemotherapeutic efficacy and reducing adverse effects. Although mesoporous silica nanoparticles (MSNs) have been known as a potential delivery system for doxorubicin (DOX), they have restricted applications due to their uncontrolled leakage and burst release from their large open pores. Herein, we engineered a smart drug-delivery system (smart MSN-drug) based on MSN-drug loading, cell membrane mimetic coating, on-demand pore blocking/opening, and tumor cell targeting strategies. The pore size of DOX-loaded MSNs was narrowed by polydopamine coating, and the pores/channels were blocked with tumor-targeting ligands anchored by tumor environment-rupturable −SS− chains. Furthermore, a cell membrane mimetic surface was constructed to enhance biocompatibility of the smart MSN-drug. Confocal microscopy results demonstrate highly selective uptake (12-fold in comparison with L929 cell) of the smart MSN-drug by HeLa cells and delivery into the HeLa cellular nuclei. Further in vitro IC 50 studies showed that the toxicity of the smart MSN-drug to HeLa cells was 4000fold higher than to the normal fibroblast cells. These exciting results demonstrate the utility of the smart MSN-drug capable of selectively killing tumor cells and saving the normal cells.

Multifunctional nanoparticle for cancer therapy

“…The extracellular pH of normal tissue is maintained at 7.4, while the pH of the TME is maintained at 6.5–6.8. 371 To improve the acidic TME, multifunctional nanoparticles with pH‐responsive bonds can be made to be cleavable in the TME and release drugs with tumor targeting. Multifunctional nanoparticles with the imine bond (C═N─) are prone to hydrolysis under acidic conditions, such as in the presence of amide bonds.…”

“…Redox sensitive : Redox‐sensitive drug delivery systems rely on redox‐sensitive chemical bonds that can be broken by GSH or ROS reduction for precise delivery and rapid drug release. 371 , 376 , 377 Due to the abnormally expressed redox substances in the tumor environment, overexpressed GSH and ROS can act as stimulators and be used in the design of multifunctional nanoparticles with redox‐sensitive bond to enhance drug release. Disulfide bonds are the most commonly used chemical bonds in multifunctional nanoparticle strategies, and following delivery to the TME, they are reduced to sulfhydryl groups at high concentrations of GSH.…”

“…Redox sensitive : Redox‐sensitive drug delivery systems rely on redox‐sensitive chemical bonds that can be broken by GSH or ROS reduction for precise delivery and rapid drug release 371,376,377 . Due to the abnormally expressed redox substances in the tumor environment, overexpressed GSH and ROS can act as stimulators and be used in the design of multifunctional nanoparticles with redox‐sensitive bond to enhance drug release.…”

Mesoporous silicas in materials engineering: Nanodevices for bionanotechnologies

“…Multi-engineered smart MSNs were developed by Gong et al. [ 193 ] to increase chemotherapeutic efficacy and reducing adverse effects of Dox in BC treatment. FA and cRGD have been conjugated via disulfide bonds to MSN surface, subsequently coated with PDA, and coupled with PNEM polymer, creating a nanoystem possessing long circulating time, redox-sensitive and active targeting properties.…”

Dual (pH- and ROS-) Responsive Antibacterial MXene-Based Nanocarrier for Drug Delivery

“…In normal tissues, the endothelial cells of capillaries are densely stacked with structural integrity, and it is difficult for invasive substances to pass through the walls of the vessel [ 20 ]. Nevertheless, tumor tissues have numerous capillaries with structural incompleteness, a broad gap in the vascular wall, and no lymphatic reflux, which result in the effortless permeation of invasive substances such as nanocarriers into cancer cells, simultaneously causing drug enhanced permeability and retention (EPR) effects at the tumor site.…”