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RGD Peptide :The 5 most important applications in tumor targeted therapy

RGD peptides are short peptides containing Arginine-Glycine-Aspartic acid (Arg-Gly-Asp), which are widely present in the organism.Extracellular matrix (ECM) and adhesion proteins in blood are the most common proteins in the human body that contain RGD peptide sequence.RGD peptide acts as an integrin to mediate the adhesion between cells and ECM between cells. At the same time has signal transmission function.

 〉〉There are more than a dozen popular RGD peptides under current research, click to enter RGD products:   RGD Peptide

The current research on RGD mainly focuses on the effect of RGD peptide on platelet function, the application of RGD peptidein antithrombotic drugs, the research of RGD peptide in the induction and regeneration of bone tissue, the research of RGD peptide in tumor metastasis and neovascularization, and application in tumor targeted therapy.


Next, we introduce the 5 most important application directions of RGD peptides:


1. Application of RGD peptide as a carrier in the treatment of tumors

The selection of targets, vectors and effector molecules in tumor targeted therapy is very important. The traditional target antigens are mostly tumor-associated antigens or tumor-specific antigens expressed on the surface of tumor cells. With the introduction of the theory that "tumor growth depends on tumor blood vessels", today, anti-tumor therapy that targets tumor new blood vessels has become a hot spot. avB3 is an ideal tumor target therapy , and its ligand RGD peptide can be used as a carrier, carrying effector molecules to inhibit tumor growth and the formation of new blood vessels.


Tumor blood vessels can express certain molecules such as ICAM-l (intercellular adhesion molecule-1), E-selectin, P-selectin, etc., under the guidance of radiation irradiation, and these molecules can also be used as targets for targeted therapy. Alternatively, the expression of certain integrins may be activated by irradiation with radiation on the tumor site, and then RGD peptide is used as its ligand to deliver the therapeutic drug to the tumor site. This is also a new idea for targeted tumor therapy.


2. Application of RGD peptide in gene targeted therapy

Recombinant adenovirus vectors are widely used in gene therapy due to their wide range of host cells, large insertable fragments, and high virus titer. However, in practical applications, they still have disadvantages such as low infection efficiency and lack of host targeting. Its modification can improve the efficiency and targeting of adenovirus infection.

One strategy to transform adenovirus is to recombine a segment of RGD peptide (such as RGD-4C) at the C-terminus of fibrin or the HI loop of the knob domain to establish a CAR-independent specific infection pathway, thereby improving the effect of Ad on tumor cells of targeting.


This RGD-modified recombinant adenoviral vector can transfect tumor cells in a non-CAR-dependent manner for some malignant tumors that are not ideal for traditional adenoviral gene therapy, such as osteosarcoma, glioma, ovarian tumor, and pancreatic cancer, and the transfection efficiency is greatly improved. It provides feasibility for clinical genetic treatment of such tumors.


3. Application of RGD peptide in tumor imaging technology

Tumor imaging technology is of great significance to the early diagnosis and discrimination of tumors, as well as to clinical and treatment. As somatostatin receptor imaging agents have been approved for clinical use, tumor receptor imaging is gaining more and more attention. Tumor receptor imaging is a combination of radionuclide-labeled ligands and specific receptors present in the tumor. It is a molecular nuclear medicine imaging diagnostic technique with strong specificity and high sensitivity.


Designed to contain RGD sequence peptides and labeled with radionuclides 125 I,99TC, 18F, etc., it is a kind of tumor receptor imaging agent with very useful value. In order to improve the image quality, DTPA, HYNIC, and dextran groups can be introduced into the radiolabeled RGD peptides, which is beneficial to the labeling of radionuclides. At present, most of the tumor ave3 receptor imaging research is in the experimental research stage, and screening the ligands of ave3 with higher affinity is the focus and difficulty that needs to be solved urgently. The realization of the preparation of one-step labeling kits for receptor ligands and their clinical application is the development direction of this research field.


4.Modification of RGD peptide

Most linear RGD peptides have a short half-life during the cycle, and their therapeutic effects and biological activities are not ideal. In order to obtain satisfactory anti-tumor effects, high doses of linear peptides containing the RGD sequence are often required, which undoubtedly increases the cost of treatment and may lead to unnecessary adverse reactions. Therefore, increasing the stability of peptide compounds and improving the biological activity of peptides are the goals for the modification of RGD peptides.


Studies have shown that changing the structure of the main body or part of the peptide to a cyclic structure can increase the stability of the linear peptide. The circular RGD polypeptide containing two disulfide bonds has the strongest inhibitory effect on neovascular endothelial cells of tumors, which is 20 times that of the circular RGD polypeptide containing single disulfide bonds and 200 times that of the linear RGD peptide. Coupling RGD peptides with other compounds is also one of the ways to increase peptide stability. After the RGD sequence peptide is coupled with polyacids, anticancer drugs, PEG, PEU, EAA, CEMA and other conjugates, its anti-cell adhesion and anti-tumor metastasis ability is enhanced.


5.The direct inhibitory effect of RGD peptide on tumor

RGD peptide can induce tumor cell apoptosis, and this process is related to the activation of caspase-3. Buckley et al. found that after RGD peptide enters the cell, it can cause the automatic processing of procaspase-3 and the activation of enzymes, which directly induce cell apoptosis.


Procaspase-3 itself contains a potential RGD combination sequence that is Asp-Asp-Met (DDM). The interaction of RGD-DDM triggers the conformational change of procaspase-3, which leads to the activation of procaspase-3 and caspase-3. In addition, the immobilized RGD peptide also has an impact on the initiation process of tumor necrosis factor (tu-mornecrosis factor, TNF)-induced apoptosis. The synthetic RGD peptide can also inhibit the action of endothelial cells and extracellular matrix, thereby inhibiting the formation of tumor neovascularization.


As a recognition site for the interaction of integrins and its ligands, RGD peptides have a good application prospect in tumor treatment. RGD peptide can directly induce tumor cell apoptosis, and its artificial modification can reduce adverse reactions, which is beneficial to exert anti-tumor effects; the specific combination of RGD peptide and integrin ave3 can target therapeutic effect molecules into tumors, It effectively reduces the damage to normal tissue cells in tumor treatment. RGD peptides can also be used to modify the structure of adenoviruses. Thereby improving the efficiency and selectivity of adenovirus transfection. In addition, the radiolabeled RGD peptide is also a promising tumor imaging agent. With the continuous maturity of phage library technology and new screening technologies. Containing RGD peptide is a promising tumor treatment drug, and its application in tumor diagnosis and treatment will be more in-depth.