Lipid–polymer hybrid nanoparticles for targeted cancer drug delivery: From design to therapeutic applications

Introduction Lipid-polymer hybrid nanoparticles ( LPHNPs ) represent a novel approach to targeted delivery of anti-cancer drugs, utilizing the advantages of polymeric and lipidic nanoparticles, combining the former’s structural stability with the latter’s high biocompatibility. In this review, the most recent developments in terms of synthesis, functionalization, characterization, targeting, and therapeutic use of LPHNPs in cancer treatment were systematically assessed. Methods According to the PRISMA guidelines, a systematic review of the literature was carried out via searching PubMed, Scopus, Web of Science, ScienceDirect, EMBASE, IEEE Xplore, Google Scholar, and ClinicalTrials. gov until December 2025. The articles eligible for inclusion were the original English-language papers and reviews concerning the LPHNP technology applied to targeted drug delivery to cancer cells. Results From the results of the reviewed articles, it was found that the core-shell architecture of LPHNPs shows high capacity for loading drugs, increased efficiency of encapsulation, prolonged release of drugs, long circulation time, and higher tumor-targeting ability. The methods used to increase cellular uptake and reduce toxicity include PEGylation and ligand targeting. For the LPHNPs, the method of synthesis that has been improved includes nanoprecipitation, solvent evaporation, and microfluidics. Theranostic delivery methods have proven successful for the treatment and diagnosis of cancer. Limitations Most of the current evidence is from preclinical studies and lacks any clinical confirmation. Inconsistency in terms of formulation, characterization, and biological evaluation of formulations may pose difficulties in comparisons. Challenges in terms of scale-up, long-term toxicity, regulation, and reproducibility limit the clinical application of these formulations. Conclusion Versatility and functionality of the LPHNPs make them suitable candidates for targeting cancer therapy. Further optimization, standardization, and clinical testing are needed for the successful application of these nanoparticles in medicine.