State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Key Laboratory of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
ACS Nano. 2023 Jun 13;17(11):10792-10805. doi: 10.1021/acsnano.3c02287. Epub 2023 Jun 2.
Natural melanin nanoparticles (MNPs) have demonstrated a potential for eliciting antitumor immune responses through inducing immunogenic cell death (ICD); however, the tumor microenvironment (TME) has been shown to inhibit T cell-mediated antitumor immunity. To address this challenge, we designed TME-responsive biodegradable melanin/MnO nanohybrids via a biomineralization process. Under near-infrared (NIR) light irradiation, the photothermal property of melanin/MnO nanohybrids triggers ICD and release of tumor-associated antigens (TAAs), while Mn and TAAs induce dendritic cell (DC) maturation to provoke immune responses. Furthermore, the immunoregulatory properties of the nanohybrids themselves are exploited to reshape immunosuppressive TME and downregulate PD-L1 through alleviation of the hypoxic and acidic TME. Although MNPs demonstrate higher photothermal killing efficiency than the nanohybrids due to their superior photothermal effect, the melanin/MnO nanohybrids exhibit significantly enhanced antitumor and antimetastatic effects , benefiting from their ability to reverse immunosuppression and induce DC maturation. Transcriptomics analysis confirmed the successful activation of immune responses. This work presents a promising approach for immunomodulation-enhanced cancer therapy through the intrinsic properties of melanin/MnO nanohybrids.
天然黑色素纳米颗粒（MNPs）已被证明具有通过诱导免疫原性细胞死亡（ICD）引发抗肿瘤免疫反应的潜力；然而，肿瘤微环境（TME）已被证明会抑制 T 细胞介导的抗肿瘤免疫。为了解决这一挑战，我们通过生物矿化过程设计了 TME 响应性可生物降解的黑色素/MnO 纳米杂化物。在近红外（NIR）光照射下，黑色素/MnO 纳米杂化物的光热特性引发 ICD 和肿瘤相关抗原（TAA）的释放，而 Mn 和 TAA 诱导树突状细胞（DC）成熟以引发免疫反应。此外，还利用纳米杂化物本身的免疫调节特性重塑免疫抑制性 TME，并通过减轻低氧和酸性 TME 下调 PD-L1。尽管 MNPs 由于其优越的光热效应而表现出更高的光热杀伤效率，但黑色素/MnO 纳米杂化物表现出显著增强的抗肿瘤和抗转移作用，这得益于它们逆转免疫抑制和诱导 DC 成熟的能力。转录组学分析证实了免疫反应的成功激活。这项工作提出了一种通过黑色素/MnO 纳米杂化物的固有特性增强免疫调节的癌症治疗的有前途的方法。
