A Dual‐Responsive Mesoporous Silica Nanoparticle for Tumor‐Triggered Targeting Drug Delivery

Abstract

A novel pH- and redox- dual-responsive tumor-triggered targeting mesoporous silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC is anchored on the surface of mesoporous silica nanoparticles via disulfide bonds, which are redox-responsive, as a gatekeeper as well as a tumor-targeting ligand. PEGylated technology is employed to protect the anchored peptide ligands. The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic-imine bond, which is pH-sensitive, are then connected via "click" chemistry to obtain TTTMSN. In vitro cell research demonstrates that the targeting property of TTTMSN is switched off in normal tissues with neutral pH condition, and switched on in tumor tissues with acidic pH condition after removing the MPEG segment by hydrolysis of benzoic-imine bond under acidic conditions. After deshielding of the MPEG segment, the drug-loaded nanoparticles are easily taken up by tumor cells due to the exposed peptide targeting ligand, and subsequently the redox signal glutathione in tumor cells induces rapid drug release intracellularly after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery system has great potential for cancer therapy.

Surface functionalized mesoporous silica nanoparticles as an effective carrier for epirubicin delivery to cancer cells

“…Additionally, controlled release feature can be enabled by using gate keepers, such as antibodies [5], oligonucleotides [6], peptides [7], enzymes [8], dendrimers [9], gold nanoparticles [10], saccharides [11], aptamers [12] and magnetic nanoparticles [13]. The ability of active targeting via different targeting agents such as monoclonal antibody [14], aptamer [15], folic acid [16], peptide [17] as well as passive targeting through EPR effect [18,19] are also well-established on the platform of MSNs. EPI is a widely used anticancer drug belonging to the anthracylines group, which is utilized for the treatment of breast, gastric, lung, ovarian and bladder cancers and non-Hodgkin´s lymphoma [20].…”

Development of docetaxel nanocrystals surface modified with transferrin for tumor targeting

“…Many researchers have studied nanoparticles (NPs) for tumor targeting 1–4. NPs can accumulate in tumor sites by the enhanced permeability and retention (EPR) effect 5,6.…”

Dual-pH responsive micelle platform for co-delivery of axitinib and doxorubicin

“…Then AXI was further encapsulated into the self-assembly micelles for antiangiogenesis. Finally, benzoic-imine bonds (Quan et al, 2010;Xiao et al, 2014;Xu et al, 2011) were used to cross-link the micelles to improve the circulatory stability and induce tumor microenvironment responsiveness. We expected that the crosslinked micelle would escort AXI and DOX selectively to tumor site.…”