Size Matters: The Impact of Nanoparticle Dimensions on Drug Delivery Efficiency in Cancer Therapy

Nanoparticle size is a central design parameter governing transport, biological interactions, and therapeutic efficacy in cancer nanomedicine. While numerous studies report size-dependent improvements in circulation time, tumour accumulation, and cellular uptake, the translation of these findings into clinical success remains inconsistent. This review critically examines how nanoparticle size influences vascular transport, tumour penetration, immune clearance, and therapeutic outcome, emphasizing mechanistic trade-offs rather than empirical trends alone. We integrate recent preclinical and clinical evidence to highlight the context-dependent limitations of widely accepted paradigms such as the enhanced permeability and retention (EPR) effect. By introducing a unifying conceptual framework that links size to competing transport and clearance processes, this review identifies why many size-optimized systems fail clinically despite promising preclinical performance. Finally, we discuss emerging strategies-including stimuli-responsive systems, patient stratification, and data-driven optimization-that may enable more reliable clinical translation of size-engineered nanomedicines.