一石四鸟：多功能多肽纳米复合材料，统一铁死亡、一氧化氮和光热，增强抗肿瘤免疫力,Advanced Functional Materials

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一石四鸟：多功能多肽纳米复合材料，统一铁死亡、一氧化氮和光热，增强抗肿瘤免疫力
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2023-05-28 , DOI: 10.1002/adfm.202304216
Meng He ₁ , Yingying Song ₁ , Wei Xu ₁ , Xueliang Zhang ₁ , Chang‐Ming Dong ₁

Affiliation

肿瘤转移和复发主要导致治疗失败，成为肿瘤学的一大挑战。肿瘤介导的免疫疗法 (IT) 的免疫原性细胞死亡 (ICD) 因解决该问题而受到广泛关注，尽管对于基于纳米颗粒的癌症 IT 而言，实现足够的 ICD 和强烈的免疫反应具有挑战性。在此，构建了一种具有近红外光热（PT）和一氧化氮（NO）和铁离子响应释放的多功能多肽配位纳米复合材料，其协同杀死癌细胞并通过PT促进的NO释放高度抑制转移性4T1细胞的侵袭和迁移和铁死亡（FT）。值得注意的是，三重 FT-NO-PT 治疗放大了 ICD 效果，并且在癌细胞和肿瘤中优于组合/单一疗法 FT-PT 和 FT，进一步激活树突状细胞成熟，⁺ T 和 CD8 ⁺ T 细胞的免疫反应和记忆效应，一石四鸟（即 FT-NO-PT-IT）。基于PCSFG的FT-NO-PT不仅能完全根除4T1原发肿瘤，还能诱导强烈的ICD、免疫启动和记忆效应，以排斥重新攻击的4T1肿瘤并抑制恶性肿瘤转移，表现出协同放大的ICD效应与强大的细胞免疫和免疫能力。通过统一的 FT-NO-PT-IT 来消除记忆效应。

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Four Birds with One Stone: A Multifunctional Polypeptide Nanocomposite to Unify Ferroptosis, Nitric Oxide, and Photothermia for Amplifying Antitumor Immunity

Tumor metastasis and relapse mainly results in therapy failure and becomes a big challenge in oncology. Immunogenic cell death (ICD) of tumors mediated immunotherapy (IT) is attracting widely for solving that problem although achieving sufficient ICD and strong immune response is challenging for nanoparticles-based cancer IT. Herein, a multifunctional polypeptide coordinate nanocomposite that possesses near infrared photothermia (PT) and responsive releases of nitric oxide (NO) and iron ions is constructed, which synergistically kills cancer cells and highly prohibits metastatic 4T1 cells invasion and migration by PT-boosted NO release and ferroptosis (FT). Remarkably, triple FT-NO-PT treatment amplifies the ICD effects and outperforms combo/monotherapy FT-PT and FT in cancer cells and tumors, which further activates dendritic cells maturation, and primed CD4⁺T and CD8⁺T cells immune responses and memory effects, playing four birds with one stone (i.e., FT-NO-PT-IT). The PCSFG-based FT-NO-PT not only fully eradicates 4T1 primary tumors, but also induces strong ICD, immune priming, and memory effects to reject rechallenged 4T1 tumors and inhibit malignant tumor metastasis, demonstrating synergistic amplified ICD effects with strong cell immunities and memory effects by a unified FT-NO-PT-IT.

更新日期：2023-05-28

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