Membrane-wrapped nanoparticles for photoacoustic imaging and photothermal therapy of triple-negative breast cancer

Triple-negative breast cancer (TNBC) is one of the most challenging subtypes of breast cancer to treat, primarily due to a lack of targeted therapies. Photothermal therapy (PTT) has emerged as a promising non-invasive strategy, wherein systemically administered light-responsive nanoparticles accumulate at the tumor site and convert externally applied near-infrared light into heat, culminating in tumor ablation. Nonetheless, the clinical application of PTT is impeded by insufficient nanoparticle accumulation within tumors. We present the development of silica core/gold shell nanoshells that are coated with TNBC cell membranes (MWNS) to enhance tumor accumulation through homotypic recognition and immune evasion. We demonstrate that MWNS preferentially target 4T1 TNBC cells over EpH4-Ev non-cancerous breast epithelial cells in vitro and accumulate more readily in orthotopic 4T1 TNBC tumors in mice following intravenous injection compared to poly(ethylene glycol)-coated nanoshells (PEG-NS). Congruently, MWNS improved PTT and photoacoustic (PA) imaging of TNBC cells in vitro, relative to PEG-NS. When assessed in an orthotopic syngeneic spontaneous metastasis tumor model in vivo, intravenously administered MWNS notably enhanced PA signals throughout the tumor volume compared to PEG-NS. Moreover, MWNS-mediated PTT inhibited tumor growth, diminished intratumoral proliferation, increased intratumoral apoptosis, and curtailed the formation of lung metastases compared with PTT mediated by PEG-NS. These findings establish MWNS as a promising biomimetic platform for precision imaging and therapy of TNBC.