Tumor Photodynamic Therapy And Photodynamic-Chemotherapy Based On Flexible Hollow Human Serum Albumin Nanocapsules

Photodynamic therapy(PDT)has attracted increasing attention for tumor treatment because of its minimal invasiveness and specific spatiotemporal selectivity,but insufficient tumor accumulation and low cellular uptake of photosensitizers limit its therapeutic efficacy.In this paper,a flexible hollow human serum albumin nanocapsule is designed and two PDT schemes are proposed based on this nanocapsule.One is to use flexible structure,human serum albumin(HSA)and catalase(CAT)to solve the problems of cellular uptake,tumor enrichment and production of reactive oxygen species(ROS)in traditional PDT.The other is to use a synergistic therapy with PDT and chemotherapy for enhanced PDT.Based on the above schemes,this paper has carried out the following two aspects:(1)Flexible hollow human serum albumin/catalase nanocapsules(HSA/CAT)are prepared via a core-assisted protein-coating approach,which are coupled with photosensitizer chlorin e6(Ce6)for PDT(HSA/CAT@Ce6).Transmission electron microscopy(TEM)images demonstrate that the HSA/CAT nanoplatforms have well dispersion,uniform diameter(310 nm),and well-defined flexible hollow structure.Thanks to the flexible property,the HSA/CAT@Ce6 nanocapsules show a higher cellular uptake than that of rigid nanoparticles.Meanwhile,the HSA/CAT@Ce6 effectively generates ROS in 4T1 cells because of the high cellular uptake and catalytic capacity,which remarkably enhances the in vitro PDT efficacy.In addition,the in vivo tumor accumulation of the HSA/CAT@Ce6is significantly increased compared to that of rigid nanoparticles and Ce6,which makes the flexible hollow HSA/CAT@Ce6 nanocapsules effectively ablate 4T1 tumor cells,demonstrating the flexible nanoplatform is very promising for enhancing PDT of tumor.(2)Flexible hollow human serum albumin nanocapsules(HHSA)are prepared via a coreassisted protein-coating approach,which are coupled with Ce6 and DOX for photodynamicchemotherapy(HHSA@Ce6-DOX).TEM images demonstrate that the HHSA nanoplatforms have well dispersion,uniform diameter(350 nm),and flexible hollow structure.UV-vis spectra shows that the Ce6 and DOX are loaded on HHSA effectively.The results of cell experiments show that compared with single PDT or chemotherapy,synergistic therapy of the HHSA@Ce6-DOX has the best therapeutic effect.