Study Of High Throughput Screening Of Peptides For Drug Delivery

A system that delivers medications to the target is a drug delivery system.A perfect delivery system can increase the effectiveness of medications while lowering dosages and side effects.In recent years,peptides have received widespread attention from researchers due to good biocompatibility.In addition,peptides also have advantages of easy synthesis,fast metabolism and low immunogenicity.The large number of functional groups on their side chains can be conjugated with drugs.Which is one of the most important directions of drug delivery systems.Although peptide drug delivery systems have achieved significant advancements,there are still some issues to be addressed,including a limited number of functional peptides,fast degradation of peptides,and short circulation half-life of peptides in vivo.The one-bead-one-compound high-throughput screening technology is widely used in the screening of targeting peptides.We are dedicated to the research of highthroughput screening technology of one-bead-one-compound for drug delivery.Based on the one-bead-one-compound technology,we developed new screening strategies and functional peptides for high-efficient drug delivery:(1)High-throughput screening method for the screening of self-assembling peptides.We designed a one-bead-one-compound peptide library combined with fluorescent probes,which can effectively identify the self-assembling peptides.The screened 8 self-assembling peptides showed the ability to form nanoparticles or nanofibers.These self-assembling peptides are non-toxic to mouse fibroblast cells and human cervical carcinoma cells within the concentration range of 200 μmol/L.These peptides are distributed in cell membrane,lysosome or nucleus,respectively,after incubated with HeLa cells.This chapter introduces a high-throughput screening method of self-assembling peptides based on one-bead-one-compound technique.The screened self-assembling peptides can be used for precise drug delivery of subcellular localization.(2)High-throughput screening of anti-adhesion peptides(AAPs).We proposed a bioinspired high-throughput screening strategy for AAPs based on phenomena that a large number of proteins in plasma do not adhere to each other.We believe that the proteins must have specific anti-adhesion sequences on their surfaces.Using fluorescently labeled serum proteins as screening probes to screen AAPs.The amino acid composition of these 7 AAPs is similar to that of the surface amino acids of two serum proteins.AAPs-modified gold nanorods(GNRs)have strong anti-adhesion ability.The AAPs significantly prolonged the half-life of GNRs in blood,which was 11.2 h longer than that of polyethylene glycol(PEG)modified GNRs.This chapter introduces a high-throughput screening method for AAPs based on the one-bead-one-compound strategy.The screened AAPs significantly reduce the protein adsorption on nanocarriers and prolong their half-life,potentially improving the delivery efficiency.(3)High-throughput screening method to screen albumin-binding peptides(ABPs)for prolonging the blood half-life.In this chapter,6 ABPs were screened from the one-bead-one-compound peptide library incubated with fluorescent labeling of human serum albumin.We investigated the binding dissociation constant and specificity of ABPs to human serum albumin.ABP1 and ABP2 were coupled with the anti-tumor drug triptorelin,and the half-life of triptorelin-ABPs was prolonged by taking the advantage of human serum albumin with a long halflife in vivo.Compared with triptorelin,the half-life of blood circulation was increased by 1.3-1.5 times.In addition,the combination therapy of triptorelin-ABPs and doxorubicin inhibited tumor growth effectively.This chapter introduces the development of ABPs and investigated their albumin binding properties.ABPs are able to act drug carriers and enhance the half-life of triptorelin(drug)through binding to albumin.In conclusion,we developed high-throughput screening technology based on one-bead-one-compound to screen functional peptides for drug delivery.We have developed a screening method for self-assembly peptides,and the screened assembly peptides may contribute to the precise subcellular drug delivery.Then,we developed a screening method for AAPs,which significantly reduces protein adsorption on the surface of nanocarriers and prolongs the blood circulation halflife of nanocarriers.In addition,we screened ABPs from one-bead-one-compound library that extend the blood circulation half-life of drugs.The new screening methods and functional peptides expand the application of peptide materials in the field of drug delivery,providing new materials and ideas for precise drug delivery.