Multifunctional Inorganic-Organic Composite Carriers for Synergistic Dual Therapy of Melanoma.

Many methods for cancer treatment have been developed. Among them photothermal therapy (PTT) has drawn the most significant attention due to its noninvasiveness, remote control activation, and low side effects. However, a limited depth of light penetration of PTT is the main drawback. To improve the therapeutic efficiency, the development of combined PTT with other therapeutic agents is highly desirable. In this work, we have designed multifunctional composite carriers based on polylactic acid (PLA) particles decorated with gold nanorods (Au NRs) as nanoheaters and selenium nanoparticles (Se NPs) for reactive oxygen species (ROS) production in order to perform a combined PTT against B16-F10 melanoma. To do this, we have optimized the synthesis of PLA particles modified with Se NPs and Au NRs (PLA-Se:Au), studied the cellular interactions of PLA particles with B16-F10 cells, and analyzed in vivo biodistribution and tumor inhibition efficiency. The results of in vitro and in vivo experiments demonstrated the synergistic effect from ROS induced by Se NPs and the heating from Au NRs. In melanoma tumor-bearing mice, intratumoral injection of PLA-Se:Au followed by laser irradiation leads to almost complete elimination of tumor tissues. Thus, the optimal photothermal properties and ROS-generating capacity allow us to recommend PLA-Se:Au as a promising candidate for the development of the combined PTT against melanoma.

Development of Nanocarrier-Based Radionuclide and Photothermal Therapy in Combination with Chemotherapy in Melanoma Cancer Treatment.

Conventional cancer therapy methods have serious drawbacks that are related to the nonspecific action of anticancer drugs that leads to high toxicity on normal cells and increases the risk of cancer recurrence. The therapeutic effect can be significantly enhanced when various treatment modalities are implemented. Here, we demonstrate that the radio- and photothermal therapy (PTT) delivered through nanocarriers (gold nanorods, Au NRs) in combination with chemotherapy in a melanoma cancer results in complete tumor inhibition compared to the single therapy. The synthesized nanocarriers can be effectively labeled with 188Re therapeutic radionuclide with a high radiolabeling efficiency (94-98%) and radiochemical stability (>95%) that are appropriate for radionuclide therapy. Further, 188Re-Au NRs, mediating the conversion of laser radiation into heat, were intratumorally injected and PTT was applied. Upon the irradiation of a near-infrared laser, dual photothermal and radionuclide therapy was achieved. Additionally, the combination of 188Re-labeled Au NRs with paclitaxel (PTX) has significantly improved the treatment efficiency (188Re-labeled Au NRs, laser irradiation, and PTX) compared to therapy in monoregime. Thus, this local triple-combination therapy can be a step toward the clinical translation of Au NRs for use in cancer treatment.