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功能化纳米材料在胰腺癌诊疗与分子成像中的应用

Functionalized Nanomaterials In Pancreatic Cancer Theranostics And Molecular Imaging.

作者信息

Nagarajan Yoghalakshmi, Chandrasekaran Natarajan, Deepa Parvathi Venkatachalam

机构信息

Department of Biomedical Sciences, Faculty of Biomedical Sciences & Technology, Sri Ramachandra Institute of Higher Education and Research (SRIHER), Tamil Nadu, Chennai, 600116, India.

Senior Professor & Former Director, Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore Campus, Tiruvalam road, Tamil Nadu, Katpadi, Vellore 632014.

出版信息

ChemistryOpen. 2025 Jan;14(1):e202400232. doi: 10.1002/open.202400232. Epub 2024 Oct 21.

Abstract

Pancreatic cancer (PC) is one of the most fatal malignancies in the world. This lethality persists due to lack of effective and efficient treatment strategies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive epithelial malignancy which has a high incidence rate and contributes to overall cancer fatalities. As of 2022, pancreatic cancer contributes to about 3 % of all cancers globally. Over the years, research has characterised germline predisposition, the origin cell, precursor lesions, genetic alterations, structural alterations, transcriptional changes, tumour heterogeneity, metastatic progression, and the tumour microenvironment, which has improved the understanding of PDAC carcinogenesis. By using molecular-based target therapies, these fundamental advancements support primary prevention, screening, early detection, and treatment. The focus of this review is the use of targeted nanoparticles as an alternative to conventional pancreatic cancer treatment due to the various side effects of the latter. The principles of nanoparticle based cancer therapy is efficient targeting of tumour cells via enhanced permeability and retention (EPR) effects and decrease the chemotherapy side effects due to their non-specificity. To increase the efficiency of existing therapies and modify target nanoparticles, several molecular markers of pancreatic cancer cells have been identified. Thus pancreatic cancer cells can be detected using appropriately functionalized nanoparticles with specific signalling molecules. Once cancer has been identified, these nanoparticles can kill the tumour by inducing hyperthermia, medication delivery, immunotherapy or gene therapy. As potent co-delivery methods for adjuvants and tumor-associated antigens; nanoparticles (NPs) have demonstrated significant promise as delivery vehicles in cancer therapy. This ensures the precise internalization of the functionalized nanoparticle and thus also activates the immune system effectively against tumor cells. This review also discusses the immunological factors behind the uptake of functionalized nanoparticles in cancer therapies. Theranostics, which combine imaging and therapeutic chemicals in a single nanocarrier, are the next generation of medicines. Pancreatic cancer treatment may be revolutionised by the development of a tailored nanocarrier with diagnostic, therapeutic, and imaging capabilities. It is extremely difficult to incorporate various therapeutic modalities into a single nanocarrier without compromising the individual functionalities. Surface modification of nanocarriers with antibodies or proteins will enable to attain multifunctionality which increases the efficiency of pancreatic cancer therapy.

摘要

胰腺癌(PC)是世界上最致命的恶性肿瘤之一。由于缺乏有效且高效的治疗策略,这种致命性一直存在。胰腺导管腺癌(PDAC)是一种侵袭性上皮恶性肿瘤,发病率高,导致了总体癌症死亡率上升。截至2022年,胰腺癌在全球所有癌症中所占比例约为3%。多年来,研究已经对种系易感性、起源细胞、前体病变、基因改变、结构改变、转录变化、肿瘤异质性、转移进展以及肿瘤微环境进行了表征,这增进了对PDAC致癌作用的理解。通过使用基于分子的靶向疗法,这些基础性进展支持了一级预防、筛查、早期检测和治疗。由于传统胰腺癌治疗存在各种副作用,本综述的重点是使用靶向纳米颗粒作为传统治疗的替代方法。基于纳米颗粒的癌症治疗原理是通过增强渗透和滞留(EPR)效应有效靶向肿瘤细胞,并因其非特异性降低化疗副作用。为了提高现有疗法的效率并修饰靶向纳米颗粒,已经鉴定了几种胰腺癌细胞的分子标志物。因此,可以使用带有特定信号分子的适当功能化纳米颗粒来检测胰腺癌细胞。一旦识别出癌症,这些纳米颗粒可以通过诱导热疗、药物递送、免疫疗法或基因疗法来杀死肿瘤。作为佐剂和肿瘤相关抗原的有效共递送方法;纳米颗粒(NPs)在癌症治疗中作为递送载体已显示出巨大的前景。这确保了功能化纳米颗粒的精确内化,从而也有效地激活免疫系统对抗肿瘤细胞。本综述还讨论了癌症治疗中功能化纳米颗粒摄取背后的免疫因素。将成像和治疗化学物质结合在单个纳米载体中的治疗诊断学是下一代药物。具有诊断、治疗和成像能力的定制纳米载体的开发可能会彻底改变胰腺癌的治疗。在不损害各个功能的情况下,将各种治疗方式整合到单个纳米载体中极其困难。用抗体或蛋白质对纳米载体进行表面修饰将能够实现多功能性,从而提高胰腺癌治疗的效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/847e/11726697/2a0b1f35dcd9/OPEN-14-e202400232-g002.jpg

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