Albumin-based nanocarriers: Singularities, synthesis methods, clinical relevance and targeting strategies in cancer.

Proteins have emerged as highly promising biomaterials for the design of drug-loaded nanocarriers due to their biocompatibility, biodegradability and reduced immunogenicity. Among them, albumin stands out as the most widely used due to its unique physicochemical and biological properties, high affinity to important cell surface receptors, structural stability, long circulation time and intrinsic binding capacities. This review provides an overview of the advantages and limitations of the main proteins that have been proposed as biomaterials for nanoparticle fabrication, with a specific focus on albumin-based systems. It explores the physicochemical characteristics of these nanosystems, receptor binding affinity and functionalization strategies for both passive and active tumor targeting. The main synthesis methods and functionalization strategies are discussed, highlighting their relevance in cancer therapy. Their clinical relevance is stressed by the US Food and Drug Administration (FDA)-approved formulations and the additional albumin-bound drugs in ongoing trials. Despite promising preclinical data and numerous active targeting approaches reported, clinical translation remains limited. This review provides the necessary information to develop improved strategies and cover the gap between preclinical research and clinical application and outlines future perspectives for enhancing the therapeutic efficacy and specificity of albumin-based drug delivery nanosystems in oncology.