The Research Of Tumor Targeting Effects Based On RGD Peptide And Antibody Binding Peptide

In recent years,the research and development of targeted drugs for tumor therapy has become a topic hotspot.However,there is a difference in the targeting ability of different kinds of drugs for the same drug target spot.Therefore,improving the targeting ability of drugs is an effective way to reduce the side effects of human body and enhance the efficacy of drugs.The work of this paper is about the research of based on RGD peptide and trastuzumab binding peptide tumor targeting effect,mainly including the following two parts:?1?The specific binding of RGD?arginine-glycine-aspartic acid?cyclic peptide with integrin?_v?₃ is an important strategy for tumor-targeting drug delivery.Herein,we designed and synthesized a series of dual-ring RGD-peptide derivatives as a drug carrier for?_v?₃ targeting.Three novel peptides showed excellent cell adhesion inhibition effect,in which,P3 exhibited 7-fold enhancement in IC₅₀ compared with cyclo?RGDfK?.Drug-loaded cytotoxicity experiment and imaging experiment indicated that such dual-cyclic RGD peptides have good tumor targeting effects.This work provides a new strategy for the design of novel RGD peptides.?2?Another work in this paper is the research of designing a Probody based on trastuzumab and its binding peptide.According to the literatures,we prepared to achieve the Probody design of peptide binding trastuzumab by synthesis of binding peptide derivatives and using the N-terminus specific site coupling reaction.It is a class of monoclonal antibody-based therapies,the antibody antigen antigen binding sites are blocked by the binding peptide and then remain inactivated?inert?in healthy tissues,but tumor-specific protease cleavage in the tumor microenvironment is thus exposing the antigen binding site,and the antibody is selectively activated.It is mainly to reduce the side effects of antibodies and antibody drugs on healthy tissues.At present,we have completed the part of chemical synthesis,but the final coupling reaction efficiency is low due to the large molecular weight and the complicated internal conformation of the antibody.Until now,we have conducted a preliminary exploration of the chemical composition of the designed trastuzumab Probody,and also give us a clear direction for the subsequent optimization.