Polydopamine-Based Multifunctional Platform for Combined Photothermal Therapy, Chemotherapy, and Immunotherapy in Malignant Tumor Treatment

We designed a multifunctional platform by coloading DOX, an antitumor drug, and imiquimod (R837), an immune adjuvant against Toll-like-receptor-7 (TLR-7), onto polydopamine nanoparticles (PDA NPs), a photothermal therapy (PTT) agent, to develop PDA/DOX&R837 NPs used as combined photothermal therapy, chemotherapy, and immunotherapy in order to enhance the cancer therapeutic effects. For a high delivery to malignant tumors, a folate ligand-receptor recognition molecule was grafted to the nanoparticle surface for a higher cellular uptake efficiency. The particle size, ζ potential, morphology, drug loading content, and drug release profiles of FA-PDA/DOX&R837 NPs were investigated. The antitumor effects under near-infrared (NIR) laser radiation were evaluated, and our results showed that a three-mode strategy combined therapy was significantly superior to single-mode therapy for tumor suppression. The synergetic toxicity of hyperthermia and DOX almost completely eliminated tumors, and together with R837, they further promoted the maturation of dendritic cells to induce a strong antitumor immune response, making tumor recurrence substantially lower than that without R837. This platform can be used as a potential targeted drug delivery system for combined cancer therapy.