Photothermal Therapy Based On RGDC Peptide Modified Gold Nanoparticles For Pancreatic Cancer

ObjectiveGold nanoparticles(AuNPs)have been widely applied to the photothermal therapy of tumor because of their unique properties,high light stability,and efficient thermal conversion.However,increasing the sensitivity and effectiveness of photothermal therapy for tumor treatment remains a huge challenge in clinical practice.It was found that the introduction of new amino acids after the primary sequence of the Arg-Gly-Asp(RGD)peptide alters the affinity of the Arg-Gly-Asp(RGD),suggesting that by modifying the RGD,the target for a specific tumor tissue can be increased.Sexuality,thereby increasing the uptake of nanoparticles by tumor cells,further increasing the enrichment of nanoparticles at the tumor site and enhancing efficacy.Pancreatic cancer cells and their surrounding matrix secrete large amounts of known proteins that are rich in cysteine.To this end,we tried to link cysteine and RGD to form a tetrapeptide of Arg-Gly-Asp-Cys(RGDC),followed by gold-bonding to the surface of gold nanoparticles.Its anti-pancreatic cancer effect under the cooperation of photothermal effect,in order to provide a new method reference for gold nanoparticle anti-pancreatic cancer in vitro and in vivo.MethodsFirstly,cysteine was introduced on the basis of RGD tripeptide to form RGDC tetrapeptide,which was directly bonded to the surface of gold nanoparticles through gold-hydraulic bonds to form composite nanoparticles(RGDC/AuNPs).The transmission electron microscopy(TEM)was used to detect whether the nanoparticles were successfully prepared,and the shape and size of the nanoparticles.The absorbance of RGDC/AuNPs was measured by UV spectrophotometer and compared with AuNPs to determine whether RGDC successfully bonded to AuNPs.Human pancreatic cancer cell line BxPC-3 was selected as the research object and the experiment was divided into two groups,namely AuNPs group and RGDC/AuNPs group.Inductively coupled plasma mass spectrometry(ICP-MS)was used to examine the uptake of gold nanoparticles before and after RGDC tetrapeptide modification in BxPC-3 cells.Furthermore,the inhibitory effect of AuNPs and RGDC/AuNPs on BxPC-3 was detected by MTT assay and live dead cell staining.Finally,the BxPC-3 cells were irradiated with a laser with a wavelength of 532 nM and a power density of 0.5 W/cm~2.The inhibitory effects of AuNPs and RGDC/AuNPs on BxPC-3 were compared by MTT assay and live dead cell staining.ResultsElectron microscopy showed that the AuNPs were successfully prepared,and the diameter of the AuNPs was about 50 nm.The UV absorption curves of RGDC/AuNPs and AuNPs are different,suggesting that AuNPs are successfully connected to RGDC.Both AuNPs and RGDC/AuNPs could be taken up by pancreatic cancer cells,and the uptake of RGDC/AuNPs by pancreatic cancer cells was nearly 2-fold higher than that of AuNPs alone.In addition,photothermal killing of pancreatic cancer cells was significantly enhanced in the RGDC/AuNPs group compared with the AuNPs group after light irradiation(P<0.05).ConclusionAuNPs and RGDC can be successfully bonded.The modification of RGDC peptide significantly increases the uptake of AuNPs by pancreatic cancer cells.RGDC/AuNPs particles may inhibit the pancreatic cancer cell BxPC-3 through a synergistic photothermal effect.This design provides a new guideline for targeted nanoparticle photothermal therapy of pancreatic cancer.