Sharma Satyam, Bhattacharya Sankha, Joshi Kajal, Singh Sanjiv
Department of Pharmacology and Toxicology, Export Promotions Industrial Park (EPIP), National Institute of Pharmaceutical Education and Research, Industrial Area, Vaishali, Hajipur, Bihar, 844102, India.
School of Pharmacy and Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India.
J Cancer Res Clin Oncol. 2023 Nov;149(17):16157-16177. doi: 10.1007/s00432-023-05331-8. Epub 2023 Aug 31.
Multiple molecular mechanisms contribute to the development of colorectal cancer (CRC), with chromosomal instability (CIN) playing a significant role. CRC is influenced by mutations in several important genes, including APC, TP53, KRAS, PIK3CA, BRAF, and SMYD4. The three molecular subtypes of this disease are CIN, MSI-H, and CIMP (CpG-island phenotype). p53 dysfunction and aberrant Wnt signalling are common characteristics of CRC carcinogenesis. Despite advances in conventional therapy, metastatic CRC remains difficult to treat due to toxicity and resistance. Theranostics for cancer could significantly benefit from nanotechnology, as it would enable more targeted, individualised care with fewer side effects. Utilising functionalized nanoparticles has enabled MRI-guided gene therapy, magnetic hyperthermia, chemotherapy, immunotherapy, and photothermal/photodynamic therapy, thereby radically modifying the way cancer is treated. Active targeting using ligands or peptides on nanoparticles improves the delivery of drugs to cancer cells. Nanostructures such as drug peptide conjugates, chitosan nanoparticles, gold nanoparticles, carbon nanotubes, mesoporous silica-based nanoparticles, silver nanoparticles, hybrid lipid-polymer nanoparticles, iron oxide nanoparticles, and quantum dots may enable targeted drug delivery and enhanced therapeutic efficacy against CRC. Nanomedicines are presently being evaluated in clinical trials for the treatment of colorectal cancer, with the promise of more effective and individualised therapies. This article examines current nanomedicine patents for CRC, including the work of Delta-Fly, Merrimack, and Pfenning, Meaning & Partner, among others. In terms of future nanomedicine research and development, ligand production, particle size, and clearance are crucial factors. Lastly, the numerous nanostructures utilized in nanomedicine for targeted drug administration and diagnostics indicate optimistic prospects for enhancing CRC treatment. The successes of nanomedicine research and development for existing colon cancer treatments are also highlighted in this review.
多种分子机制促成了结直肠癌（CRC）的发生发展，其中染色体不稳定性（CIN）起着重要作用。CRC受到多个重要基因（包括APC、TP53、KRAS、PIK3CA、BRAF和SMYD4）突变的影响。该疾病的三种分子亚型为CIN、微卫星高度不稳定（MSI-H）和CpG岛甲基化表型（CIMP）。p53功能障碍和异常的Wnt信号传导是CRC致癌作用的共同特征。尽管传统治疗取得了进展，但转移性CRC由于毒性和耐药性，治疗仍然困难。癌症的治疗诊断学可从纳米技术中显著受益，因为它能够实现更具针对性、个性化的治疗，且副作用更少。利用功能化纳米颗粒已实现了磁共振成像（MRI）引导的基因治疗、磁热疗、化疗、免疫治疗以及光热/光动力治疗，从而从根本上改变了癌症的治疗方式。在纳米颗粒上使用配体或肽进行主动靶向可改善药物向癌细胞的递送。诸如药物肽缀合物、壳聚糖纳米颗粒、金纳米颗粒、碳纳米管、介孔二氧化硅基纳米颗粒、银纳米颗粒、脂质-聚合物杂化纳米颗粒、氧化铁纳米颗粒和量子点等纳米结构可实现靶向药物递送并增强对CRC的治疗效果。目前纳米药物正在进行治疗结直肠癌的临床试验评估，有望实现更有效、个性化的治疗。本文研究了当前用于CRC的纳米药物专利，包括Delta-Fly、Merrimack以及Pfenning, Meaning & Partner等公司的工作。在未来纳米药物的研发方面，配体生产、粒径和清除率是关键因素。最后，纳米医学中用于靶向药物给药和诊断的众多纳米结构表明，增强CRC治疗具有乐观前景。本综述还强调了纳米医学研发在现有结肠癌治疗方面取得的成功。
