Engineering Alkoxyphenacyl-Polycarbonate Nanoparticles for Potential Application in Near-Infrared Light-Modulated Drug Delivery via Photon Up-Conversion Process

Abstract

Photoresponsive delivery systems that are activated by high energy photo-triggers have been accorded much attention because of the capability to achieve reliable photoreactions at short irradiation times. However, the application of a high energy photo-trigger (UV light) is not clinically viable. Meanwhile, the process of photon-upconversion is an effective strategy to generate a high energy photo-trigger (in-situ) through exposure to clinically relevant near-infrared (NIR) light. In this regard, we synthesized photon upconverting nanocrystals (UCNCs) that were subsequently loaded into photoresponsive nanoparticles (NPs) that were prepared using alkoxyphenacyl-based polycarbonate homopolymer (UCNC-APP-NPs). UCNC loading affected resultant NP size, size distribution, colloidal stability but not the zeta potential. The efficiency of NIR-modulated drug delivery was impacted by the heterogenetic nature of the resultant UCNC-APP-NPs which was plausibly formed through a combination of UCNC entrapment within the polymeric NP matrix and nucleation of polymer coating on the surface of the UCNCs. The biocompatibility of UCNC-APP-NPs was demonstrated through cytotoxicity, macrophage activation, and red blood cell lysis assays. Studies in tumor-bearing (nu/nu) athymic mice showed a negligible distribution of UCNC-APP-NPs to reticuloendothelial tissues. Further, distribution of UCNC-APP-NPs to various tissues was in the order (highest to lowest): Lungs > Tumor > Kidneys > Liver > Spleen > Brain > Blood > Heart. In all, the work highlighted some important factors that may influence the effectiveness, reproducibility and biocompatibility of drug delivery systems that operate on the process of photon-upconversion.