Abdullah K M, Sharma Gunjan, Singh Ajay P, Siddiqui Jawed A
Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Mol Cancer. 2025 Jun 9;24(1):169. doi: 10.1186/s12943-025-02368-w.
Cancer is among the leading causes of death worldwide, with projections indicating that it will claim 35 million lives by the year 2050. Conventional therapies, such as chemotherapy and immune modulation, have reduced cancer mortality to some extent; however, they have limited efficacy due to their broad mode of action, often resulting in cytotoxic effects on normal cells along with the malignant tissues, ultimately limiting their overall optimal therapeutic efficacy outcomes.Rapid advances in nanotechnology and an evolving understanding of cancer mechanisms have propelled the development of a diverse array of nanocarriers to vanquish the hurdles in achieving sophisticated drug delivery with reduced off-target toxicity. Nanoformulations can deliver the anti-cancer agents precisely to the tumor cell by integrating a multitarget approach that allows for tissue-, cell-, or organelle-specific delivery and internalization. Despite the immense interest and unmatched advancements in modern oncology equipped with nanomedicines, only a few nanoformulations have successfully translated into clinical settings. A major reason behind this shortcoming is the lack of a rationale design incorporating smart, responsive targeting features, leading to a compromised therapeutic window due to inefficient internalization or erroneous intracellular localization with unsuccessful payload release. This review aims to summarize the recent perspective of nanomedicine and its translation to clinical practice, with a particular focus on the evolution of strategies used in tumor targeting from traditional EPR-based passive mechanisms to advanced active and multi-stage approaches. We highlight the coupling of organelle-specific and stimuli-responsive nanocarriers, discuss the potential of biomimetic and cell-mediated delivery systems, and also shed light on technologies such as microfluidics, tumor-on-chip models, and AI-assisted synthesis. Finally, this review explores translational hurdles ranging from biological and manufacturing challenges to regulatory bottlenecks and outlines how innovative modeling systems and engineering solutions can bridge the gap from bench to bedside in cancer nanotherapeutics.
癌症是全球主要死因之一,据预测,到2050年癌症将导致3500万人死亡。传统疗法,如化疗和免疫调节,在一定程度上降低了癌症死亡率;然而,由于其作用方式广泛,它们的疗效有限,常常对正常细胞以及恶性组织产生细胞毒性作用,最终限制了其总体最佳治疗效果。纳米技术的快速发展以及对癌症机制认识的不断深入,推动了多种纳米载体的开发,以克服在实现复杂药物递送并降低脱靶毒性方面的障碍。纳米制剂可以通过整合多靶点方法,将抗癌药物精确递送至肿瘤细胞,实现组织、细胞或细胞器特异性递送和内化。尽管配备纳米药物的现代肿瘤学引起了极大关注并取得了无与伦比的进展,但只有少数纳米制剂成功转化为临床应用。这一缺陷背后的一个主要原因是缺乏包含智能、响应性靶向特征的合理设计,由于内化效率低下或细胞内定位错误以及有效载荷释放失败,导致治疗窗口受损。本综述旨在总结纳米医学的最新观点及其向临床实践的转化,特别关注从基于传统增强渗透与滞留(EPR)的被动机制到先进的主动和多阶段方法在肿瘤靶向中所使用策略的演变。我们强调细胞器特异性和刺激响应性纳米载体的结合,讨论仿生和细胞介导递送系统的潜力,还阐述了微流控、芯片上肿瘤模型和人工智能辅助合成等技术。最后,本综述探讨了从生物学和制造挑战到监管瓶颈等转化障碍,并概述了创新建模系统和工程解决方案如何在癌症纳米治疗中弥合从实验室到临床的差距。