Phototriggered Release of Tumor-Imaging and Therapy Agents from Lyophilized Multifunctional Polyacrylamide Nanoparticles.

Abstract

The success of polyacrylamide nanoparticles in drug delivery spurred the creation of variations in surface functional groups. We report herein a simple, reproducible, and efficient approach for the creation of modifiable nanoparticles that are characterized by their long-term stability and high loading efficiency. In our experiments, a hydrophobic photosensitizer, such as 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was able to be postloaded at more than 90% efficiency across all types of nanoparticles (NPs). Moreover, the NPs have tunable release kinetics, ranging from 9% to 23%, released by 96 h in 1% serum albumin, depending on the surface modification used. Additionally, it was observed that the NPs had a photorelease mechanism where >60% of the payload was released when exposed to at least 2 J of light. This held true with the photosensitizer and hydrophobic chemotherapeutics like curcumin. To test the impact these modifications have in vitro, two different bladder cancer cell lines were chosen (UMUC3 and T24). These nanoparticles increase the efficacy of the photosensitizer by 4-fold in UMUC3, with the cationic and amino-functionalized particles having the highest efficacy. This increase in efficacy, high uptake, and favorable subcellular localization makes the cationic modification of the nanoparticle extremely attractive for future studies.