Development and characterization of pH-responsive nanocarriers for chemo-photothermal combination therapy of acidic tumors.

The combination of photothermal therapy and chemotherapy has been considered a promising strategy for improving the excellent antitumor activities of these treatments. In this study, we developed a new simple type of pH-sensitive chemo-photothermal combination agent capable of repeated exposures to a near-infrared (NIR) laser and evaluated its anticancer efficacy in vitro and in vivo. Doxorubicin (Dox) and gold nanoclusters (GNCs) were successfully co-loaded into pH-sensitive nanoparticles (poly(ethylene glycol)-poly[(benzyl-l-aspartate)-co-(N-(3-aminopropyl)imidazole-L-aspartamide)] (PEG-PABI)), resulting in a particle size of approximately120 nm with a narrow size distribution. The dual drug-loaded nanoparticles (Dox/GNC-loaded PEG-PABI micelles (Dox/GNC-Ms)) showed consistent pH-sensitive properties and heat generation efficiency after repeated NIR laser exposure. In particular, GNC-M has improved photothermal stability while maintaining high photothermal conversion efficiency, addressing the shortcomings of previous gold nanoparticles. As the concentration of GNC-Ms, irradiation light exposure time, and light source intensity increased, the amount of heat generated and the anticancer effect increased. When Dox was encapsulated with GNCs (Dox/GNC-Ms), a faster drug release rate under acidic pH conditions and a strong synergistic effect against U87MG cells were observed. When the Dox/GNC-M system was extended to in vivo studies, it effectively increased the temperature of the tumor tissue under near-infrared irradiation and showed excellent anticancer efficacy. Therefore, the Dox/GNC-M system could be a simple but promising strategy for chemo-photothermal combination treatment capable of targeting acidic tumors.

Drug-Dependent Morphological Transitions in Spherical and Worm-Like Polymeric Micelles Define Stability and Pharmacological Performance of Micellar Drugs.

Significant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy is not adequately addressed. This work addresses this gap by assessing pharmacological efficacy of polymeric micelles with spherical and worm-like morphologies. It is observed that poly(2-oxazoline)-based polymeric micelles can be elongated over time from a spherical structure to worm-like structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. The role of different morphologies on pharmacological performance of drug loaded micelles against triple-negative breast cancer and pancreatic cancer tumor models is further evaluated. Spherical micelles accumulate rapidly in the tumor tissue while retaining large amounts of drug; worm-like micelles accumulate more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug-micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles.