5-alminolevulinic acid (5-ALA) based photodynamic therapy by multifunctional hollow mesoporous nanoparticles (HMSNPs)

Abstract

This study aims to synthesize multifunctional hollow mesoporous nanoparticles (HMSNPs) that are incorporated with 5-aminolevulinic acid (5-ALA) for photodynamic therapy applications against skin cancer cells. The HMSNP prepared had nano-channels that are aligned perpendicularly and connected to the internal hollow core, facilitating loading and releasing of 5-ALA. The multifunctional HMSNP allowed a drug loading capacity of approximately 3wt%. Folic acid conjugated polyethylene glycol (PEG+FA) was be coated on HMNSP surface when the partially charged amino groups of PEG+FA undergo electrostatic interactions with amine groups in neutral conditions. PEG+FA can prevent premature drug release by blocking the nanoparticles’ nano-channels. Acting as a targeting ligand, folic acid gives drug carriers the ability to be bound and internalized selectively into cancer cells. In vitro drug delivery comparison testings were performed using high folic acid receptor expression B16F10 cells lines (positive control, FA+) and low folic acid expression HEK293 cell lines (negative control, FA-). Results showed that targeted drug delivery to B16F10 cells through folic acid receptor meditated cellular endocytosis is effective. Such pH-sensitive drug release minimizes premature drug release and potential side effects caused by it. On top of that, 5-ALA incorporated HMSNPs (5-ALA@HMSNP-PEG+FA) also showed greater amounts of protoporphyrin IX (PpIX) were accumulated in cancer cells and phototoxicity that is that is close to that of 5-ALA alone. Hence such multifunctional nanoparticles show great potentials for controlled and targeted drug delivery in skin cancer treatment.