A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2-Positive Breast Cancer.
Li ZhaoFei ChangYao TongJiawei YinJiawen XuHui LiLutao DuYanyan JiangPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.
Keyphrases
- positive breast cancer
- cancer therapy
- photodynamic therapy
- oxidative stress
- cell proliferation
- cell death
- epidermal growth factor receptor
- small molecule
- end stage renal disease
- drug delivery
- drug release
- cell cycle arrest
- immune response
- signaling pathway
- reactive oxygen species
- induced apoptosis
- ejection fraction
- newly diagnosed
- chronic kidney disease
- tyrosine kinase
- pi k akt
- high throughput
- endothelial cells
- dna damage
- primary care
- prognostic factors
- ischemia reperfusion injury
- drug resistant
- randomized controlled trial
- systematic review
- gene expression
- squamous cell carcinoma
- radiation therapy
- dna methylation
- stem cells
- gold nanoparticles
- metal organic framework
- dendritic cells
- risk assessment
- toll like receptor
- mass spectrometry
- bone marrow
- silver nanoparticles
- multidrug resistant
- endoplasmic reticulum stress
- pain management
- long non coding rna
- protein protein
- human health
- replacement therapy
- liquid chromatography
- heat stress
- high frequency
- risk factors