Efficient delivery of gold nanoparticles by dual receptor targeting.

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Targeted delivery of inorganic nanoparticles, particularly of gold, may find wide utility in a number of biomedical applications due to their unique physicochemical and optoelectronic properties. [1-6] However, efficient delivery of a threshold amount of such particles is required for successful biomedical applications including imaging, detection/diagnosis and therapy. [7, 8] Efficient delivery of gold nanoparticles may be achieved by simultaneous targeting of multiple receptors on the cancer cells. [9] Hence, selection of appropriate targets is crucial for successful application of multiple/dual receptor targeted drug delivery system. Herein, we demonstrate the fabrication and characterization of gold nanoconjugates containing EGFR (epidermal receptor growth factor) and FR (folate receptor) antibodies on a single gold core, as a proof of principle study, to enhance the loading of gold nanoparticles (AuNPs) to EGFR and FR expressing cancer cells. We further demonstrate that the dual receptor targeted system (DRTS) is more efficient in delivering AuNPs to EGFR and FR expressing cancer cells than their corresponding single receptor targeting systems (SRTS). Such selective delivery of GNPs could be utilized in numerous biomedical applications such as detection, diagnosis and therapy. The folate receptor α (FRα) and epidermal growth factor receptor (EGFR) is known to be overexpressed in a number of malignancies including ovarian cancer. [10] Farletuzumab, a monoclonal antibody to FRα is in Phase III clinical trials both alone or in combination with platinum/taxane chemotherapy for the patients experiencing recurrence. [11] Several monoclonal antibodies directed against EGFR (trastuzumab, cetuximab, pertuzumab, and panitumumab) and small molecule tyrosine kinase inhibitors (erlotinib and gefitinib) have been investigated and are currently in different phases of clinical trials in ovarian cancer. [12] Thus, FR and EGFR represent important targets for tumor-specific delivery of anticancer drugs. Herein, we demonstrate, as a proof of principle study, fabrication and characterization of a dual receptor targeted system (DRTS) and demonstrate that it is much more efficient in delivering AuNPs to EGFR and FR expressing ovarian cancer cells Skov3-ip and OVCAR-5 than their corresponding single receptor targeting systems (SRTS). Such selective delivery of AuNPs has the potential to be used in numerous biomedical applications including detection, diagnosis and therapeutics.