PLLA@PDA-DOX Nanobubbles for Ultrasound Imaging Combined Chemo-Photothermal Therapy

The photothermal conversion capability of polydopamine (PDA) was exploited to load the anticancer drug doxorubicin (DOX) onto its surface via π-π stacking and hydrogen-bond interactions, yielding a PDA-DOX complex. In this study, biocompatible poly-L-lactic acid (PLLA) was employed as a shell material to fabricate multifunctional PLLA composite PDA-DOX (PLLA@PDA-DOX) nanobubbles with integrated functions of ultrasound imaging, photothermal therapy, and chemotherapy. The fabricated nanobubbles exhibited a uniform mean diameter of 489.30 ± 6.96 nm with a Polydispersity index (PDI) of 0.226 ± 0.01 and a DOX loading efficiency of 3.27%. Acute toxicity evaluation in mice revealed that the maximum tolerated dose of PLLA@PDA-DOX nanobubbles was markedly higher than the clinical equivalent dose, showing no detectable toxicity or allergic reactions. Under near-infrared (NIR) laser irradiation, the inhibition rate of HCCLM3 cells increased from 50.1% to 64.45%, indicating enhanced therapeutic efficacy through the combined effects of photothermal therapy and chemotherapy. Moreover, compared with the free DOX group, the survival rate of LX-2 cells in the composite nanobubble group significantly increased from 18.9 ± 1.56% to 68.8 ± 3.08%, suggesting that the PLLA@PDA-DOX nanobubbles effectively reduced the direct cytotoxicity of DOX by preventing its immediate contact with cells. Collectively, the results confirm that PLLA@PDA-DOX nanobubbles possess excellent biocompatibility, robust ultrasound imaging performance, and enhanced antitumor efficacy under NIR irradiation. This multifunctional nanosystem demonstrates promising potential as an integrated platform for simultaneous cancer diagnosis and therapy.