Novel fibronectin-targeted nanodisk drug delivery system displayed superior efficacy against prostate cancer compared with nanospheres

Currently,prostate cancer is the most frequently diagnosed cancer in males and chemotherapy is often essential for treating advaneed prostate cancer.However,common chemotherapies for prostate cancer suffer from serious adverse effects due to poor drug targeting ability and tissue penetration,even with the help of conventional drug delivery systems.Here,encouraged by recent studies showing possible drug retention and tissue pen etration advan tages of unconventional non-spherical nan oparticles over conventional spherical nan oparticles,we design and construct a novel non-spherical nano disk drug delivery system for treating prostate cancer.norder to enhance tumor-targeting capability,these nanodisks are further modified with targeting peptide,Cys-Arg-Glu丄ys?Ala peptide with N-methylated Glu(CR(NMe)EKA),which recognizes extracellular matrix fibronectin and its complexes specifically expressed on the walls of tumor vessels and in tumor stroma.Compared with conventional nano spheres,the nano disks achieve much higher drug accumulati on at prostate tumor sites.When loaded with paclitaxel,the CR(NMe)EKA-modified nan odisks display superior an titumor efficacy to free paclitaxel,unmodified nan odisks and nano spheres.In summary,our study provides an attractive therapeutic strategy for targeted therapy against prostate cancer with simple preparation,high efficiency and low toxicity,and supplements a theoretical support for treatments realized by different shaped nano platforms.Our study also offers valuable data for understa nding biological effects of non-spherical nano disks and highlights the great pote ntial of unconventional nan oparticles in biomedical applicati ons.

Co-delivery of TRAIL and paclitaxel by fibronectin-targeting liposomal nanodisk for effective lung melanoma metastasis treatment

Melanoma is a highly aggressive cancer which often forms metastatic tumors in the lung,leading to sharply reduced patients'survival rate.Effectively treating these tumors thus could improve late stage melanoma with lung metastasis.In this study,we fabricated a Cys-Arg-Glu-Lys-Ala with N-methylated Glu(CR(NMe)EKA)decorated disk shaped nano vehicle to co-deliver tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and paclitaxel(PTX)to lung melanoma tumor sites(TRAIL-[ND-PTX]^(CR(NMe)EKA)).These nanodisks displayed better tumor-targeting and penetration capability than spherical nanoparticles,while the fibronectin-targeting CR(NMe)EKA motif also increased the tumor accumulation of loaded drugs.The combined usage of TRAIL and PTX both killed tumor cells and reduced local nutrition supply,leading to stronger overall anti-tumor effect.This TRAIL-[ND-PTX]^(CR(NMe)EKA)system performed remarkably better than free paclitaxel and also significantly elongated survival rate of melanoma lung metastasis bearing mice,without displaying significant toxicity.Hence,this designing strategy and the fabricated nanoplatform possess potential for further development.