pH-Sensitive Drug Delivery System Based on Mesoporous Silica Modified with Poly-L-Lysine (PLL) as a Gatekeeper

Abstract

<jats:p>In this work, we synthesized a novel pH-triggered drug delivery system to enhance the bioavailability of the anticancer drug doxorubicin (DOX) through the gatekeeper poly-L-lysine (PLL) on the pore entrances of mesoporous silica nanoparticles (MSNs). Firstly, mesoporous silica was selected as the inorganic support for drug loading. Secondly, PLL was employed as the gatekeeper to control the cargo transport. In a neutral environment, the PLL brushes became shrunken and formed a dense barrier on the pore entrances of PLL/MSNs, which closed the pores and thus prevented the release of cargo. In an acidic environment, the cargo was released from the carrier PLL/MSNs because the pore entrances were opened by the swollen PLL brushes. The DOX-loaded PLL/MSNs (PLL/MSNs-DOX) showed 1.5 times higher drug release under acidic condition (pH = 4) than under neutral condition (pH = 7). During the drug release experiment for 48 h under acidic condition, PLL/MSN-DOX released about 50% of the drug after 9 h and approximately 85% after 24 h, whereas pristine MSNs loaded with DOX (MSNs-DOX) released about 50% of the drug after 30 min and reached equilibrium after 24 h. The MSNs also demonstrated their effectiveness in storing anticancer drugs until the desired environmental trigger is present. Therefore, the pH-responsive MSNs have great potential as a targeting cancer therapy.</jats:p>

Glucosamine Modified the Surface of pH-Responsive Poly(2-(diethylamino)ethyl Methacrylate) Brushes Grafted on Hollow Mesoporous Silica Nanoparticles as Smart Nanocarrier

“…To achieve a controlled drug release in specific tumor sites, mesoporous silica has been modified with pH-responsive polymer brushes, affording a gatekeeper to open the pores in either lower pH or higher temperature conditions [28][29][30]. Nam-Kyoung et al reported the synthesis of a novel pH-triggered drug delivery system by grafting poly-L-lysine on the pore entrances of MSNs as a drug gatekeeper [31]. In addition, the synthesis of a pH-responsive diblock copolymer, i.e., 2-(tert-butylamino)ethyl methacrylate-b-poly(ethylene glycol) methyl ether methacrylate, was reported by Alswieleh et al [32].…”

Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment

“…Gatekeeping molecules, such as acid-degradable polymers, polyelectrolytes, pH-sensitive linkers and others, are protonated by small pH changes, which alter the molecule’s overall solubility, enabling thedrug release at a particular site. In a noted attempt to illustrate this, Lee and colleagues investigated the DOX delivery using poly-L-lysine-gated MSNPs, noticing a pH decrement and polymer-swelling-mediated drug release [ 133 ]. Another significant attempt from Chen and team created pH-responsive MSNPs with “release–stop–release” tenability using ZnO quantum dot dissolution in acidic conditions to assist the drug release.…”

Chemical and green synthesis of gold nanoparticles for mRNA delivery in vitro

“…In addition to stabilising the NP, PLL has multiple amine groups that at physiological pH become protonated, allowing the binding of the anionic phosphates of the nucleic acid via electrostatic interactions. This also enhances the AuNP uptake by the negatively charged cellular membrane [8]. Furthermore, the addition of the biocompatible, synthetic, and hydrophilic polyethylene glycol (PEG) sterically stabilises the NP [9].…”