B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC

• Published in: Journal of nanobiotechnology Vol. 21; no. 1; pp. 1 - 378
• Main Authors: Chen, Bing, Zheng, Kaifan, Fang, Shubin, Huang, Kangping, Chu, Chengchao, Zhuang, Junyang, Lin, Jin, Li, Shaoguang, Yao, Hong, Liu, Ailin, Liu, Gang, Lin, Jizhen, Lin, Xinhua
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 17.10.2023; BioMed Central; BMC
• Subjects: Ablation; Analysis; Angiogenesis; Antibodies; Apoptosis; B7H3/CD276; Bioavailability; Cancer; Cancer therapies; Care and treatment; Cell culture; Cell cycle; Chemo-photothermal therapy; Chemotherapy; Cognitive enhancement; Conjugates; Diagnosis; Doxorubicin; Doxorubicin conjugates; Drug delivery; Drug delivery systems; Drug resistance; Drug therapy; Drugs; Efficiency; Fibroblasts; Gene mutations; Gold; Gold nanocage; Health aspects; Hydration; Hydrogen-ion concentration; Hyperthermia; Immune checkpoint; Lasers; Lung cancer; Lung cancer, Non-small cell; Medical prognosis; Methods; Microenvironments; Molecular weight; NMR; Non-small cell lung carcinoma; NSCLC; Nuclear magnetic resonance; Particle size; Patient outcomes; pH effects; Photochemotherapy; Physiology; Polyethylene glycol; Prognosis; Small cell lung carcinoma; Spectrum analysis; Therapeutic targets; Toxicity; Transmission electron microscopy; Tumor cells; Tumors; Vehicles; Xenotransplantation; Iran; United States
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-023-02078-9

The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.