KE-CHENG CHENYang, Shu-JyuanShu-JyuanYangSHIH HUNG YANGPai, Jui-AnJui-AnPaiMING-JIUM SHIEH2025-03-172025-03-172025-04https://scholars.lib.ntu.edu.tw/handle/123456789/725723Lung cancer (LC) is the predominant cause of cancer-related fatalities globally, with the highest death rates in both genders, primarily attributed to smoking. The non-kinase transmembrane cell surface glycoprotein, CD44, enhances LC cell migration and invasion, leading to drug resistance and an unfavorable prognosis. This research formulated a cisplatin-loaded gold nanoshell (HCP@GNS) integrated with hyaluronan (HCP@GNS@HA) to enhance targeting capability and realize a synergistic effect of chemo-photothermal therapy (chemo-PTT) against LC. The coating of hyaluronic acid (HA) facilitated the uptake of HCP@GNS@HA into CD44-rich cancer cells, maintaining the superior photothermal conversion capacity of HCP@GNS nanoparticles for hyperthermia and photothermal eradication of tumor tissues under near-infrared exposure. As a nanocarrier, HCP@GNS@HA exhibited high biocompatibility and hemocompatibility, showing stronger cytotoxicity than either the free drug or photothermal therapy alone when combined with NIR irradiation, especially at high cis-diamminedichloroplatinum (II) (CDDP) concentrations. The chemo-PTT mediated by HCP@GNS@HA effectively curtailed tumor growth without adverse effects, significantly mobilizing B cells, DC cells, macrophages, natural killer (NK) cells, and NKT cells in the distal tumor against tumor growth. In conclusion, the developed hyaluronic acid (HA)-coated gold nanoshells could potentially serve as a promising candidate for nanomedicine, tackling both primary and distal LC growth.enChemotherapyCombination therapyGold nanoshellHuman serum albuminHyaluronanPhotothermal therapy[SDGs]SDG3journal article10.1016/j.ijbiomac.2025.14011439837437