Nature Sub-Journal: Peptides take you deep into tumors

Tumor cells are more likely to ingest peptides with small biochemical molecules Scientists are using this to develop new cancer treatments Deep tumor Scientists have been trying to understand and treat cancer for a long time Although the survival rate of cancer is gradually increasing, people have not found the perfect treatment The challenge is to get cancer drugs to where they need treatment most, and to get them into cells effectively Drugs in the blood often reach only part of the tumor This is because the internal pressure of the tumor is higher and the fluid tends to flow out, which makes it difficult for the drugs in the blood to spread in In addition, because most cancer drugs are toxic, the dosage should not be too large Kathlynn brown and Michael McGuire of the University of Texas have developed novel peptides for cancer imaging and treatment through an ingenious approach, published in nature's scientific reports Targeted drugs that can recognize cancer cells and deliver drugs into them have many obvious advantages Previously, people used monoclonal antibodies to target cancer cells, but antibody modification is more cumbersome and costly, and it may also cause hypersensitivity reaction due to post-translational modification For this reason, only 10 monoclonal antibodies have been approved by FDA for cancer treatment (recommended reading: a new anti-cancer strategy for Chinese scholars) In this case, researchers began to focus on peptides Peptides are smaller than antibodies, less toxic and antigenic, easy to modify, and easy to synthesize in large quantities Unique approach Through phage display technology, the researchers constructed a large-scale random library, in which each phage clone expressed a unique peptide They then treated eight cell lines of non-small cell lung cancer (NSCLC) with these phages The key to this research is that the researchers only amplify and sequence the phages in the cell lysate, so as to select the peptides that can bind to the cell surface and internalize "The advantage of this scheme is that you don't need to use imaging to judge the internalization of molecules." Brown said Finally, the researchers found 11 peptides that can bind NSCLC cells and other cancer cells, and their affinity can be comparable to that of monoclonal antibodies Surprisingly, despite the lack of screening for non cancer cells, these peptides are able to distinguish between cancer cells and non cancer cells However, researchers don't know where the specificity of these peptides comes from Build tools After verifying the specificity and affinity of these peptides, researchers began to add a variety of chemical and biological molecules to the peptides "There is no change in the behavior of these peptides after attachment," McGuire reports For example, they attached a copper-64 radionuclide to a polypeptide and performed PET imaging in an active object The researchers point out that this will be a valuable tool for the detection of metastasis sites, because metastasis is often too small to be detected by traditional methods Now, researchers are developing the best drug carrying peptide for drug delivery They have successfully delivered adriamycin and paclitaxel to tumor cells "Drug precursors become inactive when they attach to the carrier, whether with antibodies or peptides," Brown said So researchers are looking for ways to make sure that when the drug is released it reaches the lysosome and activates there Polypeptides are easily removed by the kidney after entering the human body But Brown's team found that modifying the amino end of the peptide significantly reduced the amount of protein taken by the kidneys, maintaining their ability to recognize and bind to tumors The team hopes to get the results into clinical trials as soon as possible.