Cancer Cell Membrane-Wrapped Nanoparticles for Photothermal Therapy and Photoacoustic Imaging of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging subtypes of breast cancer to treat, primarily due to a lack of targeted therapies. Photothermal therapy (PTT) has emerged as a promising noninvasive 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 noncancerous 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 by ∼7X compared to PEG-NS. Moreover, MWNS-mediated PTT inhibited tumor growth by ∼1.7X, diminished intratumoral proliferation by 2X, increased intratumoral apoptosis by 1.8X, and curtailed the formation of lung metastases by 1.8X compared with PTT mediated by PEG-NS. These findings establish MWNS as a promising biomimetic platform for precision imaging and therapy of TNBC. With ongoing development, image-guided PTT mediated by MWNS could improve the prognosis for patients suffering from advanced TNBC or other solid tumor cancers that are refractory to existing therapies.