Targeted Delivery of Dendritic Polyglycerol–Doxorubicin Conjugates by scFv-SNAP Fusion Protein Suppresses EGFR⁺ Cancer Cell Growth

Abstract

Development of effective polymer-based nanocarriers for the successful application in cancer therapy still remains a great challenge in current research. In the present study we present a dendritic polyglycerol-based multifunctional drug immunoconjugate that specifically targets and kills cancer cell lines expressing epidermal growth factor receptor (EGFR). The nanocarrier was provided with a dendritic core as a multifunctional anchoring point, doxorubicin (Doxo) coupled through a pH-sensitive linker, a fluorescence marker, poly(ethylene glycol), as solubilizing and shielding moiety, and a scFv antibody conjugated through the SNAP-Tag technology. The study provides the proof of principle that SNAP-tag technology can be used to generate drug-carrying nanoparticles efficiently modified with single-chain antibodies to specifically target and destroy cancer cells.

Radionuclide therapy using 131I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression

“…Several types of nanoparticles, such as metal-, polymer-, and lipid-based nanoparticles, have been developed to deliver therapeutic agents, including chemotherapeutic agents, radionuclides, photosensitizers, and siRNA. Targeting ligands/moieties, such as peptides, antibodies, or antibody fragments, can be attached to nanoparticles to improve therapeutic efficacy (Hussain et al 2013). In an attempt to increase specificity, liposomes, which are spherical vesicles formed by lipid bilayers, have been conjugated to monoclonal antibodies or antibody fragments for specific delivery to target cells.…”

Structural analysis of doxorubicin-polymer conjugates

“…Therefore, the task of delivering doxorubicin directly to the tumor site, while maintaining high efficacy combined with low systemic exposure is of a major challenge [14][15][16][17][18].…”

Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

“…30 A previous report also found that the cytotoxicity of targeted scFv-425-SNAP-PGDoxo-PEG (a dendritic, polyglycerol based multifunctional doxorubicin immunoconjugate that specifically targets and kills cancer cell lines expressing epidermal growth factor receptor), was lower compared to that of the control doxorubicin, but the specificity was higher. 31 It should be noted that the IC 50 value of TMAB-PEG-PAMAM-PTX was lower than that of PEG-PAMAM-PTX due to the receptor-mediated specific cellular uptake of TMAB-PEG-PAMAM-PTX by BT474 cells. These results suggest that the TMAB-modified PAMAM dendrimer can be used to specifically deliver anticancer drugs to cells overexpressing HER2.…”