Biomimetic Nanoclusters with Vitamin A Modification for Efficient Drug Delivery: Design, Characterization and Cellular Evaluation

Nanodrug delivery systems have become a focus in the treatment of complex chronic diseases because of their advantages in improving drug stability, prolonging circulation time, and achieving precise targeting. However, conventional carriers generally have problems such as limited drug loading capacity, uneven distribution, and restricted clinical translation. In this study, a novel vitamin A-modified micelle was constructed and further coated with a red blood cell membrane to form a biomimetic nanocluster, designed to achieve efficient drug loading and precise delivery. The results showed that the system had a regular spherical structure, with particle sizes concentrated in the range of 100–150 nm, a PDI below 0.2, and a zeta potential of about −30 mV, demonstrating good dispersion stability. Compared with the control group, vitamin A modification significantly enhanced receptor-mediated cellular uptake, while the biomimetic membrane further improved immune evasion ability, resulting in about a 1.5-fold increase in intracellular fluorescence intensity compared with unmodified micelles. CCK-8 assays indicated that the IC₅₀ values of the biomimetic nanoclusters in HepG2 and MCF-7 cells were reduced by more than 40% compared with free DOX, while toxicity to normal L-02 cells was markedly lower, showing a higher therapeutic index. In conclusion, this study achieved, for the first time, the combination of >90% drug loading capacity with high targeting. The findings confirmed that the synergistic strategy of vitamin A modification and biomimetic membrane coating can overcome the limitations of conventional carriers between stability and efficacy, providing a scalable approach and potential clinical application value for the precise treatment of complex chronic diseases and tumors.