Fucoidan-based, tumor-activated nanoplatform for overcoming hypoxia and enhancing photodynamic therapy and antitumor immunity

Multifunctional nanoplatforms combined with photodynamic therapy (PDT) and anticancer drugs have shown great promising in cancer therapy. However, their efficacy is limited by the low specificity, low oxygen levels, and a tolerant tumor immune microenvironment. Herein, we developed a biocompatible theranostic nanoplatform (FM@VP) based on co-assembly of a nanocomplex formed by a functional polysaccharide fucoidan and a bioreducible polyamidoamine (PAMAM) dendrimer, a photosensitizer verteporfin (VP), and MnO₂ nanoparticles (a tumor microenvironment responsive oxygen evolving nanomaterial) into a multifunctional nanoparticle cluster. The dendrimer-fucoidan polyionic nanocomplex (DFPN) specifically targeted P-selectin-overexpressed triple-negative breast cancer (TNBC) and the tumor-associated vasculature, and was sensitive to glutathione (GSH) in tumor. More importantly, this FM@VP nanocomplex simultaneously overcame tumor hypoxia, suppressed oncogenic signaling, and attenuated tumor-mediated immunosuppression, resulting in improving therapeutic efficacy of PDT while enhancing antitumor immunity and anti-metastasis. This discovery provides a powerful strategy for synergetic cancer targeting/photodynamic/immunotherapy and could serve as a safe clinical translational approach.