Deng Bo, Kong Youpeng, Ma Yingying, Zhan Yijie, Sun Yitong, Wang Rudan, Huang Pengyu, Liu Lanxia
State Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.
School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.
J Nanobiotechnology. 2025 Jul 1;23(1):480. doi: 10.1186/s12951-025-03568-8.
Despite significant advancements in oncology, cancer remains a leading global health burden, necessitating innovative therapeutic strategies. Here, we present a novel carrier-free tumor-targeted nanomedicine system (DPA NPs) for tumor-targeted chemoimmunotherapy, formed by self-assembly of a conjugate synthesized with doxorubicin (DOX), tumor-homing peptide iRGD, matrix metalloproteinase 2 enzyme responsive peptide (MMP2), and adjuvant monophosphoryl lipid A (MPLA). The results demonstrated that DPA NPs exhibited a stable unique 3D nanostructure with tumor microenvironment (TME)-responsive properties. DPA NPs could efficiently deliver DOX to tumor cells, inducing immunogenic cell death (ICD) and simultaneously triggering tumor specific immune response. Meanwhile, MPLA amplified the anti-tumor immunity, significantly inhibiting tumor growth and metastasis. When combined with immune checkpoint inhibitors (ICIs), DPA NPs further enhanced the therapeutic outcomes in a B16 melanoma model, demonstrating remarkable suppression of tumor growth, metastasis inhibition and recurrence prevention. Mechanistic investigations across multiple biological hierarchies conclusively further confirmed the synergistic therapeutic effect. This study demonstrated that DPA NPs provide a precise, multifunctional nanoplatform for tumor-targeted combination therapy, highlighting their potential for clinical translation in cancer treatment.
尽管肿瘤学取得了重大进展，但癌症仍然是全球主要的健康负担，因此需要创新的治疗策略。在此，我们提出了一种用于肿瘤靶向化学免疫治疗的新型无载体肿瘤靶向纳米药物系统（DPA纳米颗粒），它由阿霉素（DOX）、肿瘤归巢肽iRGD、基质金属蛋白酶2酶响应肽（MMP2）和佐剂单磷酸脂质A（MPLA）合成的共轭物自组装而成。结果表明，DPA纳米颗粒呈现出具有肿瘤微环境（TME）响应特性的稳定独特三维纳米结构。DPA纳米颗粒能够有效地将DOX递送至肿瘤细胞，诱导免疫原性细胞死亡（ICD），同时触发肿瘤特异性免疫反应。同时，MPLA增强了抗肿瘤免疫力，显著抑制肿瘤生长和转移。当与免疫检查点抑制剂（ICI）联合使用时，DPA纳米颗粒在B16黑色素瘤模型中进一步提高了治疗效果，显著抑制了肿瘤生长、转移并预防了复发。跨多个生物学层次的机制研究最终进一步证实了协同治疗效果。本研究表明，DPA纳米颗粒为肿瘤靶向联合治疗提供了一个精确的多功能纳米平台，突出了其在癌症治疗中临床转化的潜力。
