Hyaluronic Acid-Modified Nanoparticles Loaded with Cabazitaxel: A Promising Nanomedicine for Malignant Prostate Tumors.

[INTRODUCTION] Prostate cancer is the most common cancer among men globally. The firstline drug, cabazitaxel (CTX), has significant side effects such as neutropenia and anemia. To address this, we aimed to develop hyaluronic acid (HA)-modified human serum albumin (HSA)-loaded CTX nanoparticles (HA-CTX NPs) to target prostate tumors with enhanced efficacy and reduced toxicity.

[METHODS] HA-CTX NPs were synthesized via a self-assembly method and optimized using unidirectional and response surface analyses. The NPs were characterized by particle size, zeta potential, and morphology. In vitro experiments evaluated the pharmacokinetics, cytotoxicity, and cellular uptake in prostate cancer cells with high CD44 expression and in HepG-2 cells with low CD44 expression. In vivo anti-tumor efficacy and biosafety were assessed using tumor-bearing models.

[RESULTS] The optimized HA-CTX NPs achieved an encapsulation efficiency of 89.2 ± 1.3%. Disulfide bonds enabled rapid drug release in the tumor microenvironment with high glutathione levels. In vitro studies showed significant cytotoxicity and targeting ability for prostate cancer cells. In vivo assays demonstrated a tumor inhibition rate of 85.31% with good biosafety.

[DISCUSSION] HA-CTX NPs exhibited superior anti-tumor efficacy and biosafety compared to Jevtana ®. The targeting ability was attributed to the high CD44 expression in prostate cancer cells. The rapid drug release in the tumor microenvironment contributed to the enhanced therapeutic effect. Limitations include the need for further long-term safety studies.

[CONCLUSION] HA-CTX NPs represent a promising nanomedicine for prostate tumor treatment, offering improved efficacy and reduced side effects compared to conventional CTX formulations.