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三阴性乳腺癌精准诊断与治疗的进展:利用 CRISPR-cas 的诊断潜力与工程化 CAR-T 细胞介导的治疗

英文原题:Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics.

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Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics.

PubMed 2023/07/15(内容时间) Environ Res Q1 · IF 8.2(JCR 2025)

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中文摘要

癌症的特征是细胞生长失控、调控通路紊乱以及基因突变的积累。不同类型癌症中的这些突变导致信号通路中断以及与细胞生长和增殖相关的蛋白质表达改变。本综述重点介绍AKT信号级联和视网膜母细胞瘤蛋白(pRb)调控级联,认为它们对于新型纳米诊疗干预具有前景。通过将最先进的基因编辑工具如成簇规律间隔短回文重复序列(CRISPR)-Cas系统与纳米材料协同结合并靶向AKT,有望显著增强癌症诊断。

此外,将改造后的CAR-T 细胞整合到多功能纳米递送系统中,为靶向抑制癌症(包括根除癌症干细胞(CSCs))提供了一种有前景的方法。在高侵袭性和转移性三阴性乳腺癌(TNBC)的背景下,本综述特别关注设计创新的纳米诊疗方案。对于TNBC的临床前和临床后检测,利用由RNA(gRNA)引导并偶联专门设计用于检测TNBC突变序列的荧光报告基因的CRISPR-Cas系统可能具有前景。

此外,一种前沿方法涉及工程化TNBC特异性iCAR和syn-Notch CAR-T 细胞,并结合共递送封装针对CSCs的条件复制型腺病毒载体(CRAdV)的混合聚合物纳米脂质体,可能呈现一种引人注目的干预策略。

因此,本综述为TNBC及其他疾病治疗中纳米诊疗领域的令人振奋的进展铺平了道路。

展开英文摘要原文

Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in signaling pathways and alterations in protein expression related to cellular growth and proliferation.

This review highlights the AKT signaling cascade and the retinoblastoma protein (pRb) regulating cascade as promising for novel nanotheranostic interventions. Through synergizing state-of-the-art gene editing tools like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system with nanomaterials and targeting AKT, there is potential to enhance cancer diagnostics significantly.

Furthermore, the integration of modified CAR-T cells into multifunctional nanodelivery systems offers a promising approach for targeted cancer inhibition, including the eradication of cancer stem cells (CSCs). Within the context of highly aggressive and metastatic Triple-negative Breast Cancer (TNBC), this review specifically focuses on devising innovative nanotheranostics.

For both pre-clinical and post-clinical TNBC detection, the utilization of the CRISPR-Cas system, guided by RNA (gRNA) and coupled with a fluorescent reporter specifically designed to detect TNBC's mutated sequence, could be promising.

Additionally, a cutting-edge approach involving the engineering of TNBC-specific iCAR and syn-Notch CAR T-cells, combined with the co-delivery of a hybrid polymeric nano-liposome encapsulating a conditionally replicative adenoviral vector (CRAdV) against CSCs, could present an intriguing intervention strategy. This review thus paves the way for exciting advancements in the field of nanotheranostics for the treatment of TNBC and beyond.

论文信息

作者
Nayak V、Patra S、Singh KR、Ganguly B、Kumar DN、Panda D、Maurya GK、Singh J
第一作者单位
Indian Council of Agricultural Research- National Institute on Foot and Mouth Disease- International Center for Foot and Mouth Disease, Bhubaneswar, Odisha, India.India
通讯作者单位
PG Department of Biotechnology, Utkal University, Bhubaneswar, Odisha, India. Electronic address: routgeorgekerry3@gmail.com.India
文献类型
综述 · 非美国政府资助研究
期刊
Environmental research2023 Oct 15
原文标识
PubMed 37437865 · DOI 10.1016/j.envres.2023.116573