An Adjustable pH-Responsive Drug Delivery System Based on Self-Assembly Polypeptide-Modified Mesoporous Silica

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Mesoporous silica nanoparticles (MSNs) offer a versatile platform for drug delivery.
• Developing pH-responsive systems is crucial for targeted therapeutic release.
• Polypeptides can be engineered for controlled self-assembly and disassembly.

Purpose of the Study:

• To develop an adjustable pH-responsive drug delivery system using MSNs and modified polypeptides.
• To investigate the use of poly(l-lysine) and poly(l-glutamate) as pH-sensitive nanovalves.
• To evaluate the drug loading, release kinetics, cellular uptake, and cytotoxicity of the developed system.

Main Methods:

• Synthesis of polypeptide-modified MSNs (PLL-MSN and PLG-MSN) via ring-opening polymerization.
• Characterization of modified MSNs using Zeta potential, XPS, solid-state NMR, and MALDI-TOF MS.
• In vitro studies including dye release assays, cellular uptake, and cytotoxicity assays with doxorubicin (DOX).

Main Results:

• Successful modification of MSNs with polypeptides confirmed by multiple characterization techniques.
• MSNs effectively loaded dye molecules, demonstrating potential for drug encapsulation.
• Controlled drug release was achieved at different pH values by adjusting the ratio of PLL-MSN to PLG-MSN.
• Cellular uptake studies showed drug localization in both cytoplasm and nucleus.
• DOX-loaded nanoparticles induced 88% cell killing in HeLa cells at a 1:1 ratio.

Conclusions:

• The developed polypeptide-MSN system functions as an effective pH-responsive drug delivery platform.
• The system allows for tunable drug release profiles based on pH and nanoparticle ratio.
• The targeted delivery and release mechanism show significant potential for cancer therapy, particularly in inducing cell death.