Drugs, including small molecule anticancer drugs, have to be delivered and released into the cytoplasm or nucleus in order to elicit a therapeutic effect. In the present study, a novel corona core‑shell nanoparticle was proposed for enhanced cellular uptake and light‑responsive intracellular release. Light‑responsive core‑shell nanoparticles, i.e., gold nanoparticles‑coated liposomes (CS), were prepared and further modified with hyaluronic acid (HA) (CCS). HA modification enhances the endocytosis of the nanoparticles by HA receptor‑expressing cells, while the plasmonic properties of gold nanoparticles enable their light‑triggered drug release. The results demonstrated that the uptake of CCS in HA receptor‑expressing MDA‑MB‑231R cells was significantly enhanced compared with unmodified CS. Nanosecond pulsed laser irradiation (700 nm; 100 mJ/cm2; 5 pulses) rapidly triggered the intracellular release of a fluorescent dye, 6‑carboxyfluorescein (6‑CF), from CCS and CS trapped in endolysosomes. The released 6‑CF was evenly distributed throughout the entire cytosol and nucleus. Finally, the cytotoxicity of doxorubicin towards MDA‑MB‑231 cells was significantly increased by CCS delivery upon pulsed laser irradiation. In conclusion, with enhanced cellular uptake and light‑triggered intracellular release, CCS significantly enhanced the therapeutic effects of doxorubicin, and may serve as a promising avenue for intracellular drug delivery.
Keywords: intracellular delivery; light responsive release; corona core-shell nanoparticle; hyaluronic acid; controlled release; cancer therapy.