Flexible Morphological Regulation of Photothermal Nanodrugs: Understanding the Relationship between the Structure, Photothermal Effect, and Tumoral Biodistribution

The morphology of nanodrugs is of utmost importance in photothermal therapy because it directly influences their physicochemical behavior and biological responses. However, clarifying the inherent relationship between morphology and the resultant properties remains challenging, mainly due to the limitations in the flexible morphological regulation of nanodrugs. Herein, we created a range of morphologically controlled nanoassemblies based on poly(ethylene glycol)-<i>block</i>-poly(d,l-lactide) (PEG-PLA) block copolymer building blocks, in which the model photosensitizer phthalocyanine was incorporated. Four different topologies were compared, namely, spherical vesicles, bowl-shaped vesicles, rodlike micelles, and vesicular tubes. The photothermal properties and <i>in vivo</i> tumoral biodistribution were investigated, revealing their relationship with the particle morphology. Finally, the tumor ablation capability of the optimized nanodrugs was demonstrated. This study represents a systematic study of the morphologically discrete regulation of nanodrugs, highlighting the importance of customization of supramolecular photothermal nanodrugs toward clinical antitumor therapy.