Lycopene Nanoencapsulation and Cancer Treatment: A Systematic Review of Preclinical Evidence

Lycopene is a natural compound with significant antitumor potential, although its poor bioavailability restricts its clinical application. To address this limitation, diverse nanoparticle-based delivery systems have been developed. This systematic review evaluated whether encapsulation improves the antitumoral efficacy of lycopene. Following PRISMA guidelines, a comprehensive search was performed in PubMed, Scopus, and Web of Science in April 2026 to identify original studies investigating the antitumoral effects of encapsulated lycopene. Included studies were original English articles evaluating encapsulated lycopene for antitumor effects against any cancer. Excluded were non-encapsulated lycopene, non-original studies, those using lycopene solely as a stabilizer, non-English texts, unavailable full-texts, or those lacking anticancer evaluation. Twenty-three eligible articles were included. Quality and risk of bias were assessed using the SciRAPnano (in vitro) and SYRCLE (in vivo) tools. Data extraction covered encapsulation system, lycopene source, in vitro and in vivo models, cytotoxicity, nanoparticle characterization, and biological activity. Encapsulated lycopene demonstrated enhanced antitumor activity across multiple cancer types, with breast cancer being the most extensively investigated (13 in vitro and 3 in vivo studies). A variety of nanocarriers were employed, including polymeric and protein-based, lipid-based, hybrid, and inorganic nanoparticles, as well as inclusion complexes. Polymeric and protein-based delivery systems were the most frequently employed (10 studies), while tomato was the most commonly used natural source of lycopene, reported in 7 studies. The main reported mechanisms involved apoptosis induction, cell cycle arrest, and antioxidant effects. Despite substantial heterogeneity among studies, the findings provide an updated overview of the current evidence supporting the antitumoral potential of encapsulated lycopene. Funding: CPP2022-009967 and DGP-PIDI-2024-00886.