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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.
Abdullah et al. (Mon,) studied this question.