Wu Dan, Zhou Jie, Zhang Zhankui, Cao Yibin, Ping Kunmin, Qi Shaolong, Du Jianshi, Yu Guocan
College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, 310014, P. R. China.
Vascular Surgery Center, The Third Hospital of Jilin University, Changchun, 130031, P. R. China.
Adv Sci (Weinh). 2025 Mar;12(11):e2408518. doi: 10.1002/advs.202408518. Epub 2025 Jan 30.
The massive amount of indoleamine 2,3-dioxygenase 1 (IDO-1) in tumor cells and tumor-associated immune cells forms a feedback loop that maintains immunosuppressive tumor microenvironment (ITM) and causes immune escape, resulting in the poor prognosis of platinum chemotherapeutics. However, the effective systemic administration of platinum drugs and IDO-1 inhibitors is strictly limited by their distinct chemical construction, different pharmacokinetic profiles, and heterogeneous distributions. Herein, a novel supramolecular method with the capability to modulate tumor microenvironment is proposed aiming at potentiating the antitumor efficacy of chemoimmunotherapy. Profiting from the dynamic and reversible merits of noncovalent interactions, IDO-1 inhibitor (IDOi) and 1,2-diaminocyclohexane-platinum(II) (DACHPt) are tailor-encapsulated into supramolecular nanoparticles (SNPs) with the aid of host-guest recognition and metal coordination, respectively, effectively increasing the drug loading and improving their pharmacokinetics. In addition to the authorized chemotherapeutical effect, DACHPt performs a systemic antitumor immune response, which is further magnified by the IDOi-reversed ITM to encourage T lymphocyte infiltration, guaranteeing long-term antitumor immune responses to improve cancer prognosis.
肿瘤细胞和肿瘤相关免疫细胞中大量的吲哚胺2,3-双加氧酶1（IDO-1）形成了一个反馈回路，维持免疫抑制性肿瘤微环境（ITM）并导致免疫逃逸，从而导致铂类化疗药物预后不良。然而，铂类药物和IDO-1抑制剂的有效全身给药受到其独特化学结构、不同药代动力学特征和异质分布的严格限制。在此，提出了一种具有调节肿瘤微环境能力的新型超分子方法，旨在增强化学免疫疗法的抗肿瘤疗效。借助非共价相互作用的动态和可逆优点，IDO-1抑制剂（IDOi）和1,2-二氨基环己烷-铂（II）（DACHPt）分别通过主客体识别和金属配位被定制封装到超分子纳米颗粒（SNP）中，有效提高了药物负载量并改善了它们的药代动力学。除了已证实的化疗效果外，DACHPt还能引发全身性抗肿瘤免疫反应，IDOi逆转的ITM进一步放大了这种反应，以促进T淋巴细胞浸润，确保长期的抗肿瘤免疫反应以改善癌症预后。
