A Novel "Mosaic-type" Nanoparticle For Selective Drug-release Targeting Hypoxic Cancer Cells

The surface potential is a double-edged sword for nanomedicine.The negative charge could protect nanoparticles from clearance before they reach the tumor tissue;however,the negative particles are hard to be phagocytosed by target cells due to the potential of cytomembrane.How to efficiently release the encapsulated drug from the negative nanoparticles to the target cells is a major challenge in advanced drug delivery studies.Here we have developed a novel “mosaic-type” nanoparticle system(GA-Cy7-NP)for selective drug-release targeting hypoxic cancer cells.In this system,a hypoxia-targeting near-infrared dye(Cy7)moiety with positive charges is conjugated to an antitumor agent gambogic acid(GA).This conjugate could self-assemble into nanoparticle with surfactin in aqueous solution where the Cy7 group is embedded in the negatively charged particle surface formed by surfactin.Most remarkably,the “mosaic-type” nanoparticles could selectively release the loaded drug conjugates into hypoxic cancer cells without particle internalization.Prostate cancer is an epithelial malignancy that occurs in the prostate gland.It is one of the malignant tumors with high incidence of male genitourinary system worldwide.Studies have shown that the broad-spectrum antineoplastic drug gambogic acid has a certain therapeutic effect on prostate,but the poor water-solubility of gambogic acid(less than 2 ?g/ml),strong stimulation,non tissue-targeting and short half-life in the body limit its clinical application.In this study,nano-particles were used to effectively encapsulate gambogic acid,to reduce many adverse reactions of the prototype drug gambogic acid.Using in vitro PC3 cell and xenograft mouse models,we demonstrate that GA-Cy7-NP exhibits enhanced drug distribution in tumor cells and excels in anti-tumor activity compared to the prototype drug when evaluated by cell proliferation,cell apoptosis and angiogenesis assay.