A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy

Abstract Background Although many treatments for breast cancer are available, poor tumour targeting limits the effectiveness of most approaches. Consequently, it is difficult to achieve satisfactory results with monotherapies. The lack accurate diagnostic and monitoring methods also limit benefits treatment. aim this study was design a nanocarrier comprising porous gold nanoshells (PGNSs) co-decorated methoxy polyethylene glycol (mPEG) trastuzumab (Herceptin®, HER), therapeutic monoclonal antibody that binds specifically human epidermal receptor-2 (HER2)-overexpressing cells. Furthermore, derivative microtubule-targeting drug maytansine (DM1) incorporated in PGNSs. Methods Prepared PGNSs were coated mPEG, DM1 HER via electrostatic interactions Au–S bonds yield DM1-mPEG/HER-PGNSs. SK-BR-3 (high HER2 expression) MCF-7 (low HER2) cells treated DM1-mPEG/HER-PGNSs, cytotoxicity evaluated terms cell viability apoptosis. selective uptake by subsequent intracellular accumulation studied vitro vivo using inductively coupled plasma mass spectrometry fluorescence imaging. multimodal imaging feasibility synergistic chemo-photothermal efficacy DM1-mPEG/HER-PGNSs investigated tumour-bearing mice. molecular mechanisms associated anti-tumour use nanoparticles elucidated. Result prepared had size 78.6 nm displayed excellent colloidal stability, photothermal conversion ability redox-sensitive release. These taken up selectively accumulated at sites vivo. Moreover, enhanced performance computed tomography (CT), photoacoustic (PA) (PT) enabled chemo-thermal combination therapy. mechanism involved induction apoptosis activation tubulin, caspase-3 heat shock protein 70 pathway. M2 macrophage suppression anti-metastatic functions observed. Conclusion nanodart-like targeting, visibility CT, PA PT powerful inhibition mediated therapy In summary, these unique nanocarriers appear have good potential as theranostic nanoagents can serve both probe novel targeted delivery system precision nanomedicine cancers.