The evolution of active targeting in cancer therapy: bridging molecular biomarkers and intelligent nanomedicine

Abstract

Despite the success of present-day chemotherapy, the shortcomings in this treatment, such as the lack of tumor selectivity, systemic toxicity, multidrug resistances, and insufficient therapeutic effects, still pose a challenge for successful clinical management of cancer. Active targeting to address these challenges has developed as a promising approach by taking advantage of biomarkers that are expressed differently on cancer cells and in the tumor microenvironment. Active targeting utilizes ligand-conjugated delivery systems that can specifically bind to receptors, which improves the accumulation of the drugs in the tumor, cellular endocytosis, and delivery of the drug into the cells. In recent years, a number of new developments in the field of nanomedicine have greatly broadened the scope for achieving active targeting by using intelligent nanocarriers containing antibody and peptide sequences, aptamers, carbohydrates, and small-molecule ligands. In addition, biomimetic nanoparticles (NPs), stimuli-responsive delivery systems, artificial intelligence (AI)-assisted design of NPs, and multifunctional theranostic platforms are revolutionizing precision oncology, providing the potential for individualized treatment approaches. A bulk of the targeted nanomedicines that have advanced from preclinical to clinical evaluation have exhibited promising clinical responses with the scope of clinical hurdles associated with tumor heterogeneity, biological barriers, manufacturability, and regulatory approval. The mini-review outlines the development of active targeting approaches, recent progress in the design of intelligent nanomedicine empowered by biomarkers, selected clinical advances, current clinical trials, and future prospects that could expedite the clinical translation of precision nanomedicine to the mainstream clinical setting.