An on-Demand Oxygen Nano-vehicle Sensitizing Protein and Nucleic Acid Drug Augment Immunotherapy

IF 27.4 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Sidi Zhang, Xinghui Wang, Xiaojing Chen, Duohuo Shu, Quankun Lin, Hanbing Zou, Jialin Dong, Bing Wang, Qianyun Tang, Huishan Li, Xiaoxiang Chen, Jun Pu, Bin Gu, Peifeng Liu
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引用次数: 0

Abstract

Hypoxia severely limits the antitumor immunotherapy for breast cancer. Although efforts to alleviate tumor hypoxia and drug delivery using diverse nanostructures achieve promising results, the creation of a versatile controllable oxygen-releasing nano-platform for co-delivery with immunostimulatory molecules remains a persistent challenge. To address this problem, a versatile oxygen controllable releasing vehicle PFOB@F127@PDA (PFPNPs) is developed, which effectively co-delivered either protein drug lactate oxidase (LOX) or nucleic acids drug unmethylated cytosine-phosphate-guanine oligonucleotide (CpG ODNs). Upon photothermal heating, this platform triggered oxygen release, thereby augmenting LOX-mediated lactate detection rates, and improving T cells infiltrating and cytokine expression. Moreover, under an oxygenated tumor microenvironment (TME), PFPNPs co-delivered with CpG ODNs effectively reprogrammed the immunosuppressive TME by repolarizing macrophages to an M1-like phenotype, promoting dendritic cells maturation, and increasing tumor-infiltrating T cells while decreasing the ratio of regulatory T cells (Tregs). Our study demonstrated that this controlled oxygen-releasing platform possessed adaptive drug-loading capabilities to meet varied immunotherapeutic demands in clinical settings.

Abstract Image

按需氧纳米载体增敏蛋白和核酸药物增强免疫治疗
缺氧严重限制了乳腺癌的抗肿瘤免疫治疗。尽管使用不同的纳米结构缓解肿瘤缺氧和药物递送的努力取得了很好的结果,但创建一个多功能可控的氧释放纳米平台,与免疫刺激分子共同递送仍然是一个持续的挑战。为了解决这一问题,开发了一种多功能氧可控释放载体PFOB@F127@PDA (PFPNPs),它可以有效地共同递送蛋白质药物乳酸氧化酶(LOX)或核酸药物未甲基化胞嘧啶-磷酸-鸟嘌呤寡核苷酸(CpG ODNs)。光热加热后,该平台触发氧气释放,从而提高lox介导的乳酸检测率,提高T细胞浸润和细胞因子表达。此外,在氧化肿瘤微环境(TME)下,ppfpnps与CpG ODNs共同递送,通过将巨噬细胞重极化为m1样表型,促进树突状细胞成熟,增加肿瘤浸润T细胞,同时降低调节性T细胞(Tregs)的比例,有效地对免疫抑制的TME进行重编程。我们的研究表明,这种可控的氧释放平台具有自适应的药物装载能力,以满足临床环境中不同的免疫治疗需求。
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来源期刊
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
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