Polydopamine-coated ferric oxide nanoparticles for R848 delivery for photothermal immunotherapy in breast cancer

Breast cancer is the most frequently diagnosed malignant cancer among women in the world (Siegel et al., 2022), which seriously threatens the lives and health of female. The ability of traditional surgery, chemotherapy, radiotherapy and hormone therapy to eradicate tumour cells is low (Borri and Granaglia, 2021), leading to drug resistance and toxic side effects (Salas-Benito et al., 2021). Therefore, new therapeutic options to improve the efficiency of cancer treatment urgently need to be explored.

Immunotherapy is a novel and promising cancer therapy treatment that can boost the host anti-tumor immune response to eliminate the primary tumors and prevent metastasis and recurrence (Paulis et al., 2013; Jo et al., 2017). Nevertheless, the clinical application of immunotherapy in the breast cancer still faces some challenges, including weak immune responses and severe adverse effects, which are attributed to the lack of immunogenicity (Wei et al., 2019). Combining immunotherapy with other therapeutic modalities, particularly photothermal therapy (PTT), has gained increasing acceptance and is expected to overcome the above limitations (Chen et al., 2020, Qu et al., 2020), and broadening the clinical applicability of immunotherapy for breast cancer.

PTT, which utilizes the absorption of near-infrared (NIR) light emitted by photothermal agents to induce a hyperthermal effect on tumour cells, has the unique advantages of enhanced selectivity and minimal invasiveness (Zhao et al., 2022). Recently, increasing evidence has confirmed that PTT not only inhibits primary tumour via thermal ablation (Vankayala and Hwang, 2018, Xu et al., 2017), but also triggers host immunity by causing the release of tumour-associated antigens. Therefore, the combination of PTT with immune therapeutic approaches is a promising method for the treatment of the breast cancer (Zhao et al., 2018).

Currently, diverse nanomaterials have been employed in PTT for against the cancer to overcome existing challenges, such as limited light tissue penetration and a lack of targeting ability. Among such nanomaterials, Fe3O4 nanoparticles, approved by FDA (Bobo et al., 2016), have been revealed to use as the excellent platform for PTT due to their high biocompatibility and biodegradability, as well as their excellent stability (Arias et al., 2018). Moreover, Fe3O4-mediated PTT has been verified to trigger an efficient antitumor immune response. Due to inadequate stimulation of the system immune response (Yang et al., 2019), PTT-immunotherapy requires further strengthening of antitumour immunity via the introduction extraneous antigen (Zhang et al., 2019). The development of a safe and effective PTT-immunotherapy approach for cancer treatment is warranted.

In this study, we developed Fe3O4@polydopamine nanoparticles (Fe3O4@PDA, NP), modified with the polyethylene glycol (PEG) and cyclic arginine-glycyl-aspartic peptide (RGD), as well as anisamide (AA) (Fe3O4@PDA-PEG-RGD/AA NP, tNP) for loading of the immune adjuvant, resiquimod (R848; R848@tNP). Notably, R848, a toll-like receptor 7/8 (TLR7/8) agonist, is useful for promoting immune responses (Ding et al., 2017, Ding et al., 2016). Then, we explored the effects and anticancer efficacy of nanoparticles against breast cancer under 808 nm NIR in vitro and in vivo, both of which were related to the tumour-associated antigens (TAA) generated via PTT. Moreover, this study explored properties of tNP as an in vivo magnetic resonance imaging (MRI) contrast agent for tumour diagnosis. This research combined PTT with immunotherapy to generate a new platform for the development of diagnostic andtherapeutic approaches for breast cancer.

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