4.8 Article

A minimalist and robust chemo-photothermal nanoplatform capable of augmenting autophagy-modulated immune response against breast cancer

Journal

MATERIALS TODAY BIO
Volume 15, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.mtbio.2022.100289

Keywords

Breast cancer; Photothermal therapy; Immunotherapy; Autophagy; Itraconazole; IR820

Funding

  1. National Key Research and Development Project of China [2020YFA0509400]
  2. Guangdong Basic and Applied Basic Research Foundation [2019B030302012]
  3. National Natural Science Foundation of China [81821002, 81790251, 82130082]
  4. 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYJC21004]

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This study demonstrates the potential of IC/IR820 NPs in breast cancer treatment. The NPs enhance therapeutic efficacy by inducing apoptosis and autophagic death, leading to inhibition of tumor recurrence.
Previously used in anti-fungal therapy, itraconazole has now been shown to be successful in treating advanced breast cancer (NCT00798135). However, its poor solubility still restricts its application in clinical treatment. There is therefore an urgent need for combined methods to enhance the therapeutic effect of itraconazole (IC) in breast cancer treatment. With this goal, co-assembled IC/IR820 NPs with synergistic photonic hyperthermia and itraconazole payloads have been constructed to overcome these shortcomings. The IC/IR820 NPs show an enhanced therapeutic effect on breast cancer by inducing reactive oxygen species (ROS)-mediated apoptosis and autophagic death. Further evaluation in a mouse model has shown impressive effects of the IC/IR820 NPs on both inhibiting tumor metastasis and activating immunity to prevent tumor recurrence. Mechanistically, itraconazole may promote both tumor cell antigen presentation through autophagy and the activation of dendritic cells to induce an immune response, which displays a synergistic effect with the immune response generated by photo -thermal therapy to inhibit tumor recurrence. This strategy of combining itraconazole and IR820 into one mini-malist and robust nanoplatform through co-assembly results in excellent therapeutic efficacy, suggesting its potential application as an alternative method for the clinical treatment of breast cancer.

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