pH/GSH-Dual-Sensitive Hollow Mesoporous Silica Nanoparticle-Based Drug Delivery System for Targeted Cancer Therapy

Abstract

The purpose of developing novel anticancer drug delivery systems (DDSs) is to efficiently carry and release drugs into cancer cells and minimize side effects. In this work, based on hollow mesoporous silica nanoparticle (HMSN) and the charge-reversal property, a pH/GSH-dual-sensitive DDS named DOX@HMSN–SS-PLL­(cit) was reported. HMSN encapsulated DOX with high efficacy and was then covered by the “gatekeeper” β-cyclodextrin (β-CD) through the glutathione (GSH)-sensitive disulfide bond. Thereafter, adamantine-blocked citraconic-anhydride-functionalized poly-l-lysine (PLL­(cit)-Ad) was decorated on the surface of the particles via host–guest interaction. The negatively charged carriers were stable in the neutral environment in vivo and could be effectively transported to the tumor site. The surface charge of the nanoparticles could be reversed in the weakly acidic environment, which increased the cellular uptake ability of the carriers by the cancer cells. After cellular internalization, β-CD can be removed by breakage of the disulfide bond in the presence of a high concentration of GSH, leading to DOX release. The preparation process of the carriers was monitored. The charge-reversal capability and the controlled drug-release behavior of the carriers were also investigated. In vitro and in vivo experiments demonstrated the excellent cancer therapy effect with low side effects of the carriers. It is expected that dual-sensitive DOX@HMSN–SS-PLL­(cit) could play an important role in cancer therapy.

Reduced Thiol Compounds – Induced Biosensing, Bioimaging Analysis and Targeted Delivery

“…For example, Li et al . prepared a nanomaterial encapsulated DOX, that uses passive targeting to enter the tumor tissue, and the high expression of GSH will promote the cleavage reactions, thus completing the targeted delivery of drugs [30] . Therefore, disease monitoring and treatment tools can be designed and developed from the cleavage reactions of RTCs, which provides a theoretical basis for the development of life and health.…”

pH and redox dual-sensitive drug delivery system constructed based on fluorescent carbon dots

“…[10][11][12] However, it is required to overcome multiple obstacles for realizing these complex steps, because the specic requirements on charge, size or stability of nanocarrier at each stage are different. [13][14][15][16] Therefore, how to incorporate multiple nano-characteristics required at each stage into one nanocarrier system for overcoming multi-stage biological barriers remains a challenge.…”

Modification of Mesoporous Silica Surface by Immobilization of Functional Groups for Controlled Drug Release

“…e ss-MONs-Dox showed better anticancer efficacy than MSNs-Dox, due to that ss-MONs have good degradability with reductive glutathione, leading to the enhancement of Dox release. Chen et al have recently reported the synthesis of pH/glutathione (GSH) dual-sensitive nanoplatform based on silica nanoparticle for targeting cancer cells [41]. e novel nanocarrier was pH-sensitive in the weakly acidic cancerous cells.…”