Preparation of PSA-DOX/ICG-Lip and Evaluation of Its Efficacy Against Cervical Cancer.

Objectives

To fabricate polysialic acid (PSA)-modified liposomes co-loaded with doxorubicin (DOX) and indocyanine green (ICG) for synergistic chemotherapy and photothermal therapy, and to enhance the anti-cervical cancer efficacy of liposomes via neutrophil targeting.

Methods

PSA-DOX/ICG liposomes (PSA-DOX/ICG-Lip) were prepared by microfluidic technology. The physicochemical properties, including drug encapsulation efficiency (EE), loading capacity (LC), particle size, polydispersity index (PDI), zeta potential, and stability, were systematically characterized. The in vitro anti-tumor activity was evaluated using cellular uptake, apoptosis assays, reactive oxygen species (ROS) detection, and a cell scratch test in HeLa and C33a cells. The in vivo therapeutic efficacy was verified using a nude mouse xenograft model of cervical cancer combined with histopathological analysis.

Results

Microfluidic preparation yielded PSA-DOX/ICG-Lip with favorable physicochemical properties: the EE and LC of DOX were 96.52 ± 0.43% and 8.70 ± 0.04%, respectively, while those of ICG were 90.72 ± 1.10% and 0.82 ± 0.02%. The average particle size was 92.68 ± 1.14 nm with a PDI of 0.04 and a zeta potential of -9.66 ± 0.46 mV. The liposomes maintained good stability in terms of EE, particle size, PDI, and zeta potential after 28 days of storage at 4 °C and room temperature, with PSA modification significantly reducing the drug leakage rate. In vitro drug release studies showed that 808 nm laser irradiation triggered a significant increase in drug release from the liposomes. ICG encapsulated in liposomes mediated localized photothermal heating, and PSA targeting precisely confined the therapeutic effect to the tumor site, minimizing damage to adjacent normal tissues. In vitro experiments demonstrated that PSA-DOX/ICG-Lip, combined with laser irradiation, significantly enhanced cellular uptake, elevated intracellular ROS levels, inhibited cancer cell migration, and induced apoptosis. In vivo studies confirmed that this formulation markedly suppressed tumor growth in nude mice, with a tumor inhibition rate of 81.5%, and exhibited good biocompatibility without obvious organ toxicity.

Conclusions

The microfluidically prepared PSA-DOX/ICG-Lip possesses high drug encapsulation efficiency, uniform particle size, good stability and sustained drug release properties. It can efficiently convert light energy into thermal energy, target neutrophils to enhance the affinity for cervical cancer cells, and exert a synergistic anti-tumor effect via the combination of chemotherapy and photothermal therapy, which provides a promising nanoplatform for the precise treatment of cervical cancer.