用于治疗癌症的免疫调节纳米凝胶-纳米系统

IF 18 1区 医学 Q1 ENGINEERING, BIOMEDICAL Bioactive Materials Pub Date : 2024-09-17 DOI:10.1016/j.bioactmat.2024.08.047
Sung Hoon Kim , Rafael T. Han , Hyung-Seop Han , Young-Min Kim
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引用次数: 0

摘要

由于肿瘤免疫微环境(TIME)的抑制,目前的癌症免疫疗法反应率很低。要解决这些不利的 TIMEs 问题,补充肿瘤相关抗原和刺激靶点的免疫细胞对于激发抗肿瘤免疫反应是必不可少的。以往的研究探索了通过多次注射和植入诱导免疫疗法的方法;然而,这些方法缺乏对患者便利性的考虑,也没有实施可微调的免疫反应控制系统,以减轻细胞因子风暴等过度炎症反应的副作用。在此背景下,我们描述了一种以患者为中心的纳米凝胶-纳米系统,该系统能够持续产生肿瘤相关抗原并释放佐剂。这是通过向癌细胞特异性地输送药物和向免疫细胞长期输送抗原/佐剂来实现的,只需一次注射就能在肿瘤部位保持适当的浓度。这种系统只需一次注射就能显示出对肿瘤的局部免疫力,提高免疫检查点阻断剂的疗效,并诱导全身性和记忆性 T 细胞反应,从而将全身性副作用降至最低。
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Immune-modulative nano-gel-nano system for patient-favorable cancer therapy

Current cancer immunotherapies exhibit low response rates attributed to suppressive tumor immune microenvironments (TIMEs). To address these unfavorable TIMEs, supplementation with tumor-associated antigens and stimulation of immune cells at target sites are indispensable for eliciting anti-tumoral immune responses. Previous research has explored the induction of immunotherapy through multiple injections and implants; however, these approaches lack consideration for patient convenience and the implementation of finely tunable immune response control systems to mitigate the side effects of over-inflammatory responses, such as cytokine storms. In this context, we describe a patient-centric nano-gel-nano system capable of sustained generation of tumor-associated antigens and release of adjuvants. This is achieved through the specific delivery of drugs to cancer cells and antigens/adjuvants to immune cells over the long term, maintaining proper concentrations within the tumor site with a single injection. This system demonstrates local immunity against tumors with a single injection, enhances the therapeutic efficacy of immune checkpoint blockades, and induces systemic and memory T cell responses, thus minimizing systemic side effects.

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来源期刊
Bioactive Materials
Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
28.00
自引率
6.30%
发文量
436
审稿时长
20 days
期刊介绍: Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.
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