Harnessing multimodality with mesoporous Silica@Polydopamine@Hyaluronic acid nano-vehicle for synergistic chemo-photothermal breast cancer therapy

Breast cancer is the primary threat to the health of women worldwide. Traditional treatment methods are limited by their toxic side effects and insufficient efficacy against metastatic tumors, and thus, there is an urgent need for breakthroughs. In this study, we designed a multifunctional nanotherapeutic platform that integrates targeted drug delivery with synergistic chemo-photothermal therapy, providing an effective paradigm for the combination of chemotherapy and photothermal therapy (PTT) for breast cancer. The core structure of the nanosystem is mesoporous silica nanoparticles (MSNs) loaded with the chemotherapeutic drug doxorubicin hydrochloride (Dox), encapsulated by a polydopamine (PDA) shell that enables near-infrared (NIR) photothermal conversion and on-demand drug release upon local NIR irradiation. The surface is finally modified with hyaluronic acid (HA) for active targeting. The HA-CD44-mediated active targeting and enhanced permeability and retention (EPR) passive targeting increase drug accumulation at the tumor site. Localized drug release within the tumor minimizes systemic toxicity and enhances the bioavailability of the chemotherapeutic drug. Importantly, the synergistic effect of PTT and chemotherapy in tumor cell inhibition has been validated by the combination index (CI), providing theoretical evidence for optimizing clinical combination treatment strategies for breast cancer. • Photothermal agent is a key component of the chemotherapeutic drug delivery system. • Enhanced tumor targeting via EPR effect and HA-CD44 active targeting. • In vitro CI analysis confirms photothermal-chemotherapy synergy. • In vivo tumor suppression effect of photothermal-chemotherapy is remarkable.