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Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks clear molecular targets and is characterized by high rates of recurrence and metastasis. Aberrant activation of the epidermal growth factor receptor (EGFR) promotes tumor progression and immune evasion in TNBC. Although EGFR inhibitors can temporarily inhibit tumor growth, compensatory signaling and treatment resistance limit their efficacy. A therapeutic strategy that regulates multiple pathways simultaneously to enhance anti-tumor immunity is needed. Selective nanoparticle delivery provides a method to increase efficacy while reducing non-specific toxicity. We have developed ND-dsRNA-VHH, a biocompatible carbon-based nanomaterial platform, capable of synergistically delivering EGFR-specific nanobodies (VHHs) and immunostimulatory double-stranded RNA - poly(I:C). The optimized ND surface chemistry supports efficient dsRNA loading and stable VHH binding, generating nanoparticles with EGFR binding specificity and serum stability. Subsequent studies have shown that ND-dsRNA-VHH induces apoptosis, oxidative stress, and immunogenic cell death, thereby activating dendritic cells. Further evaluation has revealed that ND-dsRNA-VHH treatment can reduce tumor growth, prolong survival, increase T cell infiltration, and transform the tumor microenvironment into a more pro-inflammatory and immunologically active state. The modular nature of this platform supports ligand exchange, enabling its wider application in EGFR-driven malignant tumors (such as glioblastoma), highlighting its potential to enhance immunotherapy by combining ICD induction and immune activation. This study was published in ACS Nano under the title "Nanodiamond-Mediated Targeted Delivery of Nanobodies and Immunostimulatory RNA for Breast Cancer Therapy".
Reference News:
DOI: 10.1021/acsnano.5c21823
