Construction and biological activity of nano micelles drug delivery system coupled with human CD40 monoclonal antibody
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Abstract:
Objective:A human CD40 monoclonal antibody, 5C11, was coupled with three kinds of polymeric micelles (PMs) containing different chemical groups respectively to construct the corresponding 5C11 coupled polymeric micelles (PM-5C11). The optimal PM for coupling with 5C11 was selected among them, and evaluate its biological activity. Methods: Three kinds of copolymers with different chemical composition were synthesized respectively to prepare the corresponding PM and PM-5C11 after coupled with 5C11. The PM-5C11 which exhibited both higher coupling efficiency and greatest biological safety was selected to be the optimal one among them. The optimal PM-5C11 was then interacted with Daudi cell line, derived from human Burkitt lymphoma, to evaluate its biological activity and the cellular uptake by Daudi cells. Results: Three kinds of PMs containing tosyl group, allyl group or carboxyl group had been prepared successfully. The coupling efficiencies of 5C11 to PMs containing tosyl group or allyl group were both higher than that to PM containing carboxyl group (\[28.08±2.24\]%, \[29.06±137\]% vs \[21.26±1.04\]%, P<0.05). The PM containing tosyl group was chosen to be the optimal one because cytotoxic reagent remained during the preparation of the PM containing allyl group. The corresponding optimal PM coupled with 5C11 to form PM-5C11, which exhibited the original bioactivity of 5C11 and could be uptaken by Daudi cells. Conclusion: Among the three kinds of PMs, the PM containing tosyl group exhibits the best biological safety and the relative higher coupling efficiency; its corresponding PM-5C11 shows the best biological activity. This PM could be the best choice for constructing the nano-drug carrier.
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Project supported by the National Natural Science Foundation of China (No.81101556), the Research Innovation Project for University Graduate Students in Jiangsu Province (No.CXZZ11 _0110), and the Science and Technology Development Project of Suzhou (No.SYSD2011084)