From Nanoparticle Design to Clinical Translation in Cancer Therapy
Jordi Puiggalı́
Abstract
Nanoparticle-based strategies have emerged as a versatile and powerful approach for cancer therapy, enabling the integration of material science, molecular biology, and immunology into multifunctional therapeutic platforms. Over the past decade, significant advances in nanoparticle design have expanded their potential beyond passive drug carriers toward systems capable of active targeting, microenvironment-responsive behavior, and immune modulation. This review provides a comprehensive and up-to-date overview of the major nanoparticle platforms developed for cancer treatment, including lipid-based, polymeric, inorganic, and bioinspired nanomaterials, with particular emphasis on their structure-property relationships and biological interactions. We discuss key targeting strategies, spanning passive, active, stimuli-responsive, and cellular or immune-mediated approaches, and analyze how nanoparticles can overcome biological barriers imposed by the tumor microenvironment, such as abnormal vasculature, dense extracellular matrix, hypoxia, and immunosuppression. Special attention is given to nanoparticle-enabled cancer immunotherapy, including vaccine delivery, mRNA-lipid nanoparticle systems, and combination strategies that integrate immunotherapy with conventional treatments. Finally, we critically examine safety, toxicity, and translational challenges that continue to limit the clinical impact of cancer nanomedicine, highlighting the importance of biologically informed design, manufacturing robustness, and regulatory considerations. By synthesizing current advances and identifying emerging trends, this review aims to provide a framework for the rational development of next-generation nanoparticle-based cancer therapies with improved clinical relevance.