ABSTRACT
Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Subject(s)
Animals , Humans , Squamous Cell Carcinoma of Head and Neck/therapy , Heterografts , Photothermal Therapy , Biomimetics , Disease Models, Animal , Head and Neck Neoplasms/therapy , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
This study aims to explore the potential of polyaspartic acid grafted dopamine copolymer (PAsp- g-DA) chelated Fe 3+ for magnetic resonance imaging (MRI) visual photothermal therapy. Polyaspartic acid grafted copolymer of covalently grafted dopamine and polyethylene glycol (PAsp- g-DA/PEG) was obtained by the ammonolysis reaction of poly succinimide (PSI), and then chelated with Fe 3+ in aqueous solution. The relaxivity in vitro, magnetic resonance imaging enhancement in vivo and photothermal conversion effect at 808 nm were investigated. The results showed that polymeric iron coordination had good near-infrared absorption and photothermal conversion properties, good magnetic resonance enhancement effect, and good longitudinal relaxation efficiency under different magnetic field intensities. In summary, this study provides a new magnetic resonance visual photothermal therapeutic agent and a new research idea for the research in related fields.