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Attachable Hydrogel Containing Indocyanine Green for Selective Photothermal Therapy against Melanoma.

ABSTRACT: Melanoma is the most lethal form of skin cancer because it spreads easily to other tissues, thereby decreasing the efficiency of its treatment via chemo-, radio-, and surgical therapies. We suggest the application of an attachable hydrogel for the treatment of melanoma whereby the size and amount of incorporated indocyanine green (ICG) for photothermal therapy (PTT) can be controlled. An attachable hydrogel (poly(acrylamide-co-diallyldimethylammonium chloride); PAD) that incorporates ICG as a near-infrared (NIR) absorber was fabricated using a biocompatible polymer. The temperature of PAD-ICG increases under 808 nm laser irradiation. The hydrogel protects the ICG against decomposition; consequently, PAD-ICG can be reused for PTT. The attachment of PAD-ICG to an area with melanoma in mice, with irradiation using a NIR laser, successfully eliminated melanoma. Thus, the data suggest that PAD-ICG is a smart material that could be used for selective target therapy against melanoma in humans.

SUBMITTER: Hwang J

PROVIDER: S-EPMC7465476 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Attachable Hydrogel Containing Indocyanine Green for Selective Photothermal Therapy against Melanoma.

Hwang Juyoung J Jin Jun-O JO

Biomolecules 20200729 8

Melanoma is the most lethal form of skin cancer because it spreads easily to other tissues, thereby decreasing the efficiency of its treatment via chemo-, radio-, and surgical therapies. We suggest the application of an attachable hydrogel for the treatment of melanoma whereby the size and amount of incorporated indocyanine green (ICG) for photothermal therapy (PTT) can be controlled. An attachable hydrogel (poly(acrylamide-co-diallyldimethylammonium chloride); PAD) that incorporates ICG as a ne ...[more]

PMID: 32751399

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Project description:BackgroundEfficient cancer therapy is sought not only for primary tumor treatment but also for the prevention of metastatic cancer growth. Immunotherapy has been shown to prevent cancer metastasis by inducing antigen-specific immune responses. Indocyanine green (ICG) has a peak spectral absorption at about 800 nm, which makes it a photothermal reagent for direct treatment of solid tumors by photothermal therapy (PTT). Since PTT alone cannot fully induce antigen-specific immune response for prevention of cancer metastasis, the combination of PTT and immunotherapy has been developed as a new strategy of cancer treatment.MethodsThermal responsive liposomes (TRL) were synthesized by incorporating ICG into the lipid bilayer and encapsulating the water-soluble immune stimulatory molecule polyinosinic:polycytidylic acid (poly I:C) in the hydrophilic core. The poly I:C- and ICG-containing TRLs (piTRLs) were analyzed according to size, and their photothermal effect was evaluated following laser irradiation at 808 nm. Moreover, the temperature-dependent release of poly I:C was also measured. For cancer therapy, CT-26 (carcinoma) and B16 (melanoma) cells were subcutaneously inoculated to build the 1st transplanted tumor in BALB/c and C57BL/6 mice, respectively. These mice received a 2nd transplantation with the same cancer cells by intravenous inoculation, for evaluation of the anti-metastatic effects of the liposomes after PTT.ResultsNear-infrared (NIR) laser irradiation increased the temperature of piTRLs and effectively released poly I:C from the liposomes. The increased temperature induced a photothermal effect, which promoted cancer cell apoptosis and dissolution of the 1st transplanted tumor. Moreover, the released poly I:C from the piTRL induced activation of dendritic cells (DCs) in tumor draining lymph node (tdLN). Cancer cell apoptosis and DC-activation-mediated cancer antigen-specific immune responses further prevented growth of lung metastatic cancer developed following intravenous transplantation of cancer cells.ConclusionThese results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases.

Project description: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.

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Attachable Hydrogel Containing Indocyanine Green for Selective Photothermal Therapy against Melanoma.

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Attachable Hydrogel Containing Indocyanine Green for Selective Photothermal Therapy against Melanoma.

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