The Construction Of Bipyramid-like Mesoporous Platinum-coated Gold Nanoparticle And Its Application In Pancreatic Cancer Photodynamic Therapy

Objective（1）The previous researches showed that the nanomaterials with high aspect ratio,high curvature radius or sharp edges and corners will have unique advantages in biological behavior.Although bipyramid-like mesoporous metal nanoparticles possessed the above characteristics,studies about the synthesis of bipyramid-like mesoporous metal nanoparticles and exploring the its biological behaviors have not been reported.The purpose of this study is to synthesize bipyramid-like mesoporous platinum coated gold nanoparticles and further explore their biological behaviors.（2）Photodynamic therapy has made some progress in pancreatic cancer.However,the efficacy of a single Ce6 treatment method is often not obvious.The purpose of this study is to use Ce6 loaded bipyramid-like mesoporous platinum coated gold nanoparticles to enhance photodynamic therapy.Methods（1）Three different shaped mesoporous platinum coated gold core-shell nanoparticles（spherical S-GP,Rod-like R-GP and bipyramid-like B-GP）were prepared with three different shapes of gold nanoparticles（spherical S-G,rod-shaped R-G and bipyramid-like B-G）as metal templates.（2）The spherical S-GP,Rod-like R-GP and bipyramid-like B-GP were co-incubated with Aspc-1 pancreatic cancer cells or 3D Aspc-1 pancreatic cancer cell spheroids,and the cell uptake efficiency and penetration depth were detected by scanning confocal microscopy and flow cytometry;The spherical S-GP,Rod-like R-GP and bipyramid-like B-GP were injected into nude mice through tail vein,and blood samples were collected at different time points.The blood circulation time of the nanoparticles was detected and analyzed;ICP-AES and near infrared small animals living imaging system were used to analyzed the accumulation of the three platinum coated gold nanoparticles in tumor tissues and major organs.（3）The[Ru（dpp）₃]Cl₂ was used to evaluated the hydrogen peroxide（H₂O₂）catalytic activity of Ce6-loaded bipyramid-like B-GP（B-P-Ce6）.The reactive oxygen species probe（DCFH-DA）was used to detect the reactive oxygen species levels of Aspc-1 cells.（4）CCK8 assay and live/dead cell staining assay were used to evaluated the photodynamic therapy efficacy of B-P-Ce6 co-incubated Aspc-1 cells.（5）Endoplasmic reticulum stress inhibitor N-acetylcysteine（NAC）was used to save B-P-Ce6 co-incubated Aspc-1 cells irradiated with 660 nm laser,and the survival effect was detected by live/dead cell staining assay.（6）The Aspc-1 pancreatic cancer tumor-bearing mice were treated by B-P-Ce6photodynamic therapy.Results（1）The all results of scanning electron microscopy,transmission electron microscopy and nitrogen adsorption-desorption curves showed that the three nanoparticles had rough surface,uniform size and obvious pore structures.（2）Compared to S-GP and R-GP,B-GP exhibited higher cellular uptake efficiency,stronger tumor penetration ability,longer blood circulation time and better tumor photothermal therapy efficacy.（3）B-GP-Ce6 showed excellent H₂O₂ catalytic activity.（4）Compared to single Ce6,B-GP-Ce6 showed better photodynamic therapy effect,and induced stronger ER stress,which could be inhibited by endoplasmic reticulum stress inhibitor N-acetylcysteine.（5）Among all therapeutic groups,the B-P-Ce6 group showed the best Aspc-1 pancreatic cancer therapeutic effect.Conclusions（1）B-GP showed outstanding biological behaviors,including higher cell uptake efficiency,longer blood circulation time,better tissue permeability,higher tumor enrichment and better tumor photothermal efficacy.（2）B-GP-Ce6 could enhance photodynamic therapy via improving oxygen supply and inducing ER stress.