Differential Surface Engineering Generates Core-Shell Porous Silicon Nanoparticles for Controlled and Targeted...

Area of Science:

• Nanotechnology
• Biomaterials Science
• Drug Delivery Systems

Background:

• Porous silicon nanoparticles (pSiNPs) offer potential for drug delivery due to their tunable properties.
• Targeted delivery systems are crucial for improving cancer therapy efficacy and reducing side effects.
• Surface modification of nanoparticles is key to achieving desired functionalities like stability, targeting, and controlled release.

Purpose of the Study:

• To develop a core-shell porous silicon nanoparticle system with differential surface modifications for targeted hydrophobic drug delivery.
• To functionalize the nanoparticle surface with an antifouling polymer and a cell-targeting peptide for enhanced cellular association and therapeutic effect.
• To investigate the drug loading, release kinetics, colloidal stability, and in vitro efficacy of the developed nanocarrier system.

Main Methods:

• Differential surface modification of porous silicon films and subsequent ultrasonication to create pSiNPs.
• Surface-initiated atom transfer radical polymerization to graft poly-N-(2-hydroxypropyl) acrylamide (polyHPAm) brushes.
• Conjugation of the cRGDfK peptide to the nanoparticle surface for targeting the αvβ3 integrin receptor.
• Loading of camptothecin, a hydrophobic anti-cancer drug, into the nanoparticle pores.

Main Results:

• The developed pSiNPs exhibited excellent colloidal stability in cell culture medium.
• In vitro drug release kinetics were successfully fine-tuned by the surface modifications.
• Confocal microscopy and flow cytometry demonstrated improved cellular association due to the cRGDfK peptide.
• Drug-loaded, peptide-functionalized nanoparticles showed enhanced cytotoxicity against C4-2B prostate carcinoma cells in both 2D and 3D models.

Conclusions:

• The developed core-shell pSiNPs represent a promising platform for targeted delivery of hydrophobic anti-cancer drugs.
• The combination of internal hydrophobic modification, external antifouling polymer, and peptide targeting enhances drug delivery efficiency and therapeutic outcomes.
• This approach offers a versatile strategy for designing advanced nanomedicines for cancer treatment.