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RC48-targeted two-dimensional black phosphorus nanoplatform for precise photothermal-immunotherapy of HER2-positive
Feiyang Xiao1, Guanyuan Chen2, Hongwei Lu1
1Department of Biomedical Engineering, College of Engineering, Shantou University, Shantou 515063, China.
Abstract:
Despite advances in targeted therapy for HER2-positive breast cancer, tumor-intrinsic resistance mechanisms including defective antigen presentation and adaptive immune suppression remain a significant challenge, constraining therapeutic efficacy. In this study, we developed a multifunctional nanotherapeutic system based on tumor-selective antibody-drug conjugate (ADC) disitamab vedotin (RC48) that co-delivered PEGylated black phosphorus (BP) and resiquimod (R848, a TLR7/8 agonist), thereby enhancing photothermal tumor ablation while activating antitumor immunity in HER2-positive breast cancer. The formed BP-PEG-RC48-R848 nanocomposites exhibited favorable photothermal stability and effectively induced the maturation of dendritic cells while promoting the secretion of pro-inflammatory M1 cytokines. In vivo fluorescence imaging demonstrated specific accumulation of the nanocomposites within HER2-positive tumors. Under near-infrared laser irradiation, the HER2-targeting nanocomposites effectively ablated primary local tumors and elicited concomitant immune activation, collectively inhibiting tumor progression in vivo. By integrating ADC drugs with photothermal-immunotherapy, the nanocomposites demonstrated enhanced precision and synergistic antitumor efficacy of HER2-positive breast cancer.
Insights
This study introduces a novel nanotherapeutic combining an antibody-drug conjugate (disitamab vedotin) with black phosphorus and resiquimod. This approach enhances photothermal therapy and activates antitumor immunity for HER2-positive breast cancer.
Area of Science:
- Oncology
- Nanomedicine
- Immunotherapy
Background:
- HER2-positive breast cancer faces resistance to targeted therapies due to immune suppression.
- Defective antigen presentation hinders effective antitumor immune responses.
Purpose of the Study:
- To develop a multifunctional nanotherapeutic system for HER2-positive breast cancer.
- To combine antibody-drug conjugate therapy with photothermal and immune activation strategies.
Main Methods:
- Development of PEGylated black phosphorus (BP) nanocomposites co-delivering disitamab vedotin (RC48) and resiquimod (R848).
- Evaluation of photothermal stability, dendritic cell maturation, and cytokine secretion.
- In vivo fluorescence imaging for tumor-specific accumulation.
- Assessment of tumor ablation and antitumor immune response under near-infrared laser irradiation.
Main Results:
- BP-PEG-RC48-R848 nanocomposites showed excellent photothermal stability.
- The system effectively matured dendritic cells and promoted M1 cytokine secretion.
- In vivo studies confirmed specific tumor accumulation, effective primary tumor ablation, and inhibition of tumor progression.
- Synergistic antitumor efficacy was observed through the integration of ADC, photothermal therapy, and immunotherapy.
Conclusions:
- The developed nanotherapeutic system integrates antibody-drug conjugate therapy with photothermal-immunotherapy.
- This approach offers enhanced precision and synergistic antitumor efficacy for HER2-positive breast cancer.
- The strategy overcomes tumor-intrinsic resistance mechanisms by activating antitumor immunity.
