Mohamed Rehab Galal Abbas, Ali Salma Mohamed, Ahmed Iman Saad, Rawas-Qalaji Mutasem, Hussain Zahid
Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.
Biomater Sci. 2025 Oct 7;13(20):5626-5664. doi: 10.1039/d5bm01176k.
Colorectal cancer (CRC) remains a major global health burden, necessitating more effective and selective therapeutic approaches. Nanocarrier-based drug delivery systems offer significant advantages by enhancing drug accumulation in tumors, reducing off-target toxicity, and overcoming resistance mechanisms. This review provides a comprehensive overview of recent advancements in nanocarriers for CRC therapy, including passive targeting the enhanced permeability and retention (EPR) effect, and active targeting strategies that exploit specific tumor markers using ligands such as antibodies, peptides, and aptamers. Additionally, various stimuli-responsive systems are explored, which leverage tumor-specific cues-such as pH, redox, enzymes, light, heat, and magnetic fields-for controlled and localized drug release. Multifunctional and hybrid platforms combining multiple targeting mechanisms and therapeutic functionalities are also discussed for their potential in theranostics and personalized medicine. Unlike prior reviews, this article emphasizes emerging ligand-engineered nanosystems, multi-stimuli-responsive designs, and translational challenges, providing a forward-looking perspective on next-generation CRC nanomedicine. While preclinical studies demonstrate encouraging outcomes, clinical translation remains limited due to challenges in scalability, biocompatibility, and tumor heterogeneity. Future research should focus on the rational design of safe, smart, and modular nanocarriers, integration of machine learning tools, and personalized approaches to maximize efficacy. Overall, the evolving landscape of nanotechnology presents promising avenues for improving CRC treatment and patient prognosis.
结直肠癌（CRC）仍然是一项重大的全球卫生负担，因此需要更有效、更具选择性的治疗方法。基于纳米载体的药物递送系统具有显著优势，可增强药物在肿瘤中的蓄积、降低脱靶毒性并克服耐药机制。本综述全面概述了用于CRC治疗的纳米载体的最新进展，包括被动靶向——增强的渗透与滞留（EPR）效应，以及利用抗体、肽和适体等配体靶向特定肿瘤标志物的主动靶向策略。此外，还探讨了各种刺激响应系统，这些系统利用肿瘤特异性线索——如pH值、氧化还原、酶、光、热和磁场——实现药物的可控和局部释放。还讨论了结合多种靶向机制和治疗功能的多功能和混合平台在治疗诊断学和个性化医学中的潜力。与以往的综述不同，本文重点介绍了新兴的配体工程纳米系统、多刺激响应设计以及转化挑战，为下一代CRC纳米医学提供了前瞻性视角。虽然临床前研究显示出令人鼓舞的结果，但由于在可扩展性、生物相容性和肿瘤异质性方面存在挑战，临床转化仍然有限。未来的研究应专注于安全、智能和模块化纳米载体的合理设计、机器学习工具的整合以及个性化方法，以最大限度地提高疗效。总体而言，纳米技术不断发展的格局为改善CRC治疗和患者预后提供了有前景的途径。
