Hyaluronan-coated gold nanoshells for enhanced synergistic effect and immunogenic cell response of chemo-photothermal therapy on lung cancer

Ke-Cheng Chen; Shu-Jyuan Yang; Shih-Hung Yang; Jui-An Pai; Ming-Jium Shieh

doi:10.1016/j.ijbiomac.2025.140114

Hyaluronan-coated gold nanoshells for enhanced synergistic effect and immunogenic cell response of chemo-photothermal therapy on lung cancer

Int J Biol Macromol. 2025 Jan 19:140114. doi: 10.1016/j.ijbiomac.2025.140114. Online ahead of print.

Authors

Ke-Cheng Chen¹, Shu-Jyuan Yang², Shih-Hung Yang³, Jui-An Pai⁴, Ming-Jium Shieh⁵

Affiliations

¹ Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
² Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan. Electronic address: [email protected].
³ Department of Oncology, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
⁴ Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.
⁵ Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Department of Oncology, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. Electronic address: [email protected].

PMID: 39837437
DOI: 10.1016/j.ijbiomac.2025.140114

Abstract

Lung 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.

Keywords: Chemotherapy; Combination therapy; Gold nanoshell; Human serum albumin; Hyaluronan; Photothermal therapy.