Strengthened binding affinity of bispecific antibody nanoplatforms improved the anti-tumor efficacy

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2024-08, Vol.494, p.153128, Article 153128
• Main Authors: Duwa, Ramesh, Choi, Jinsol, Shrestha, Prabhat, Nguyen, Thoa Thi Kim, Bastatas, Lyndon D., Gwon, Youngdae, Park, Soyeun, Jeong, Jee-Heon, Yook, Simmyung
• Format: Article
• Language: English
• Subjects: Binding affinity; Bispecific antibodies; Docetaxel; Nanoparticle; Poly(lactic-co-glycolic acid)
• ISSN: 1385-8947
• DOI: 10.1016/j.cej.2024.153128

•Bispecific antibodies target dual disease mediators, thwarting escape mechanisms.•CTX & HER-decorated DRT-DTX-PLGA-NPs deliver DTX to cancer cells.•CTX & HER dual conjugation on PLGA-NPs enhances binding affinity additively and synergistically boosts adhesion energy.•DRT-DTX-PLGA-NPs show superior uptake and cytotoxicity vs. single receptor-targeted NPs.•DRT-DTX-PLGA-NPs exhibit enhanced tumor retention, inhibiting tumor growth significantly more than single-ligand NPs. Dual receptor targeting (DRT) strategies use bispecific antibodies to simultaneously target two distinct disease mediators and thereby overcome major escape mechanisms evident in mono-targeted therapy. DRT enhances the binding affinity between the ligand and receptors and the specific targeted delivery of nanoparticles (NPs) into cancer cells. In this study we developed anti-EGFR cetuximab (CTX) and Herceptin (HER) decorated poly(lactic-co-glycolic acid) (PLGA) NPs for the targeted delivery of docetaxel (DTX), which we call DRT-DTX-PLGA-NPs, and we quantified their binding affinity with EGFR and HER2 positive cancer cells. The binding affinity assay indicated that dual conjugation of CTX and HER on PLGA-NPsenhanced the binding affinity between the NPs and cells additively in terms of affinity and synergistically in terms of adhesion energy, compared with PLGA-NPs conjugated with CTX and HER. Furthermore, the DRT-DTX-PLGA-NPs exhibited higher cellular uptake and higher cancer cell cytotoxicity than the single receptor-targeted NPs. In SW480 xenograft mice, the DRT-DTX-PLGA-NPs were more concentrated and retained at the tumor site due to their enhanced binding affinity, and as a result, tumor volume and tumor weight were significantly inhibited compared with tumors treated with the single-ligand targeted NPs. Therefore, DRT-NPs have the potential to improve cancer therapy by providing high affinity between NPs and cells and improving selectivity compared with single-ligand-targeted NPs.