Combining photothermal therapy and immunotherapy against melanoma by polydopamine-coated Al₂O₃ nanoparticles

Abstract

Photothermal therapy (PTT) can be an effective antitumor therapy, but it may not completely eliminate tumor cells, leading to the risk of recurrence or metastasis. Here we describe nanocarriers that allow combination therapy involving PTT and immunotherapy. Nanocarriers are prepared by coating Al2O3 nanoparticles with non-toxic, biodegradable polydopamine, which shows high photothermal efficiency. A near-infrared laser irradiation can kill the majority of tumor tissues, resulting in the release of tumor-associated antigens. The Al2O3 within the nanoparticles, together with CpG, acts as an adjuvant to trigger robust cell-mediated immune responses that can help eliminate the residual tumor cells and reduce the risk of tumor recurrence.Methods: The characteristics and photothermal performance of polydopamine-coated Al2O3 nanoparticles were examined after one-step preparation. Then we studied their internalization, photothermal toxicity and immunostimulatory activity in vitro. For in vivo experiments, these nanocarriers were injected directly into B16F10 melanoma allografts in mice to ensure specific localization. After photothermal irradiation on day 0, mice were subcutaneously injected with CpG adjuvant on day 1, 3 and 5. Tumor volumes and number of living mice were recorded every two days. Moreover, various immune responses induced by our combined therapy were tested for mechanism research.Results: 50% of mice after our combined treatment successfully achieved the goal of tumor eradication, and survived for 120 days, which was the end point of the experiment. Mechanism studies demonstrated the combined therapy efficiently led to dendritic cell maturation, resulting in the secretion of antibodies and cytokines as well as the proliferation of splenocytes and lymphocytes for anti-tumor immunotherapy.Conclusion: Taken together, these results demonstrated the promise of our combined photothermal therapy and immunotherapy for tumor shrinkage, which merited further research.

Prussian blue nanoparticle-based antigenicity and adjuvanticity trigger robust antitumor immune responses against neuroblastoma

“…There have been a few published reports, including ours, that describe the combination of PTT with immunotherapies for the treatment of cancer, including the use of CpG-coated nanoparticles utilized for PTT. These include hollow gold nanoshells, 34 CpG-loaded MoS 2 nanosheets, 35 graphene oxide, 36 Al2O3 nanoparticles, 37 and hollow CuS nanoparticles 5 . Compared with earlier studies, our work is distinct for the following reasons: 1) Prussian blue is a United States FDA-approved material as Radiogardase® and listed as an essential medicine by the World Health Organization as a radioactive poisoning antidote, 38 which indicates the safety of working with PBNPs, 2) PBNPs are biodegradable, 9 which mitigates concerns associated with the long-term fate and associated toxicities of nanoparticles within the body, 39 3) we describe a facile method for coating CpG onto the PBNPs that enables the simultaneous delivery of tumor cell death, antigenicity, and adjuvanticity in a single nanoparticle, and 4) PBNPs combined with toll-like receptor agonists have not previously been applied to treat neuroblastoma.…”

Metal‐Containing Polydopamine Nanomaterials: Catalysis, Energy, and Theranostics

“…[ 72 ] PDA can also effectively load active ingredients, such as drug molecules, dyes, peptides, and DNAs through either physical adsorption or chemical conjugation for chemotherapy, immunotherapy, and photodynamic therapy. [ 70a,73 ] In addition, PDA‐based nanomaterials are known to bind with a variety of metal ions and radioisotope simultaneously, which allows the use for ferroptosis, catalytic therapy, imaging purpose, and radiotherapy. [ 74 ] By integration those imaging and therapy features together, MPDAs were constructed for various imaging‐guided therapies.…”

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

“…The within the NPs, together with CpG that acts as an adjuvant to trigger robust cell-mediated immune responses, can help eliminate the residual tumour cells. Fifty percent of mice, after going through combined therapy, achieved goal tumour eradication and survived for 120 days, which was the end goal of the experiment [ 215 ]. Photothermal therapy can be combined with blockage checkpoints to achieve an even more enhanced antitumour effect.…”