Fabrication of a pH/Redox-Triggered Mesoporous Silica-Based Nanoparticle with Microfluidics for Anticancer Drugs Doxorubicin and Paclitaxel Codelivery

Abstract

A pH/redox-triggered mesoporous silica nanoparticle (MSN)-based nanoplatform has been fabricated for doxorubicin/paclitaxel (DOX/PTX) codelivery. In this drug-delivery system (DDS), PTX is covalently attached to the surface of DOX loaded MSN via a linker with disulfide bond. By directly attaching PTX to MSN, we can significantly enhance the PTX́s loading degree and achieve the optimum drug loading ratio to DOX, therefore, to generate the best synergistical effect. More importantly, PTX and the linker act as a redox-sensitive “gate” to precisely control the release profile of DOX and PTX. Subsequently, polystyrenesulfonate (PSS) is electrostatically coated to DOX loaded MSN-PTX in microfluidics to achieve acidic pH responsive, because the free amino group on MSN surface has a protonation state at acidic pH, and the electrostatic interaction will be destroyed at pH 5. In addition, PSS can also neutralize the surface zeta potential, thus reduce the nonspecific endocytosis of healthy cells. By evaluating cell viability in cancer cell BT549 and healthy breast cell MCF-10A, we observed that the nanoparticles can selectively release DOX and PTX and eliminate cancer cells, while they will have negligible effect on the healthy breast cells, due to the acidic and redox microenvironment in cancer cells. Overall, we have developed a nanoplatform for precise DOX/PTX combination therapy with high selectivity between cancer cells and healthy cells.

Multimodal Decorations of Mesoporous Silica Nanoparticles for Improved Cancer Therapy

“…Besides, a redox- and pH-sensitive dual response MSN system has been developed by Li and colleagues using ammonium salt to seal the pores [ 255 ]. Yan et al have fabricated a pH/redox-triggered MSN nanosystem, for the codelivery of doxorubicin and paclitaxel in cancer cells [ 256 ]. Additionally, Anirudhan et al have exploited both temperature and ultrasound sensitive gatekeepers for the surface modification of MSN [ 257 ].…”

Synthesis and Surface Engineering of Inorganic Nanomaterials Based on Microfluidic Technology

“…The release kinetics of therapeutic molecules from porous nanoparticles can be controlled by coating stimuli-responsive (e.g., light, heat, temperature, pH, and redox) polymers on the particle surface [ 162 , 163 ]. In these settings, Zhang and coworkers deposited polystyrene sulfonate (PSS) on chemotherapeutic drugs encapsulating MSN by using microfluidic technology ( Figure 12 a) [ 164 ]. The PSS can completely block the open pores of the MSNs and prevent the premature leakage of chemotherapeutic drugs during blood circulation.…”

“… ( a ) Schematic illustration for the synthesis of DOX@MSN-PTX and the microfluidic fabrication of DOX@MSN-PTX@PSS (reproduced from [ 164 ], with permission from the American Chemical Society, 2020). ( b ) Schematic illustration for the construction of glucose-responsive delivery system and the orchestrated cascade for diabetic wound care (reproduced from [ 165 ], with permission from the Royal Society of Chemistry, 2019).…”

Preparation and Applications of Organo-Silica Hybrid Mesoporous Silica Nanoparticles for the Co-Delivery of Drugs and Nucleic Acids

“…In 2020, polystyrenesulfonate (PSS) coated MSNs were engineered for the dual delivery of Dox/paclitaxel (PTX) [ 53 ]. In this DDS, PTX was covalently attached to the surface of Dox loaded MSNs via a linker with disulfide bond ( Figure 14 ).…”

“… Polystyrenesulfonate coated MSN for the co-delivery of Dox/ paclitaxel (PTX). Reproduced from reference [ 53 ] . Copyright 2020 American Chemical Society.…”