Self-targeted smart polyester nanoparticles for simultaneous Delivery of photothermal and chemotherapeutic agents for efficient treatment of HCC.

Advances in nanotechnology offer promising strategies to overcome the limitations of single-drug therapies in hepatocellular carcinoma (HCC) and other cancers such as multidrug resistance and variable drug tolerances. This study proposes a targeted nanoparticle system based on a poly(β-aminoester) (PβAE) core and a hyaluronic acid (HA) shell, designed for the codelivery of doxorubicin (DOX) and indocyanine green (ICG) to effectively treat HCC. These nanoparticles demonstrated remarkable physicochemical and colloidal stability, pH- and temperature-responsive release, enhanced cellular uptake, and drug retention within tumors. Upon near-infrared (NIR) irradiation, the photothermal conversion of ICG elevated local tumor temperatures up to 53.6 °C, enhancing apoptotic cell death significantly compared to chemotherapy alone (p < 0.05). Furthermore, the dual delivery system significantly enhanced therapeutic efficacy, as evidenced by a marked decrease in tumor growth in vivo compared to controls (p < 0.01). These findings illustrate that the HA/PβAE/DOX/ICG nanoparticles are not only able to precisely target tumor cells but also overcome the limitations associated with traditional chemotherapies and photothermal treatments, suggesting a promising avenue for clinical translation of cancer therapy.