title: Acetate ions enhance load and stability of doxorubicin onto PEGylated nanodiamond for selective tumor intracellular controlled release and therapy.
abstract: A successful drug delivery device for cancer chemotherapy should ideally be able to load drugs highly, bring the drug preferentially into tumor cells and reduce its distribution in normal tissue to enhance therapeutic efficacy. To this purpose, a novel protocol for DOX-loaded PEGylated nanodiamond (ND-PEG-DOX/NaAc, NPDA) was fabricated using sodium acetate medium. The NPDA nanoparticles exhibited a maximum loading efficiency (99 wt%) with ultra-low drug leakage (7 wt%). Examination by confocal microscope and flow cytometer showed that the NPDA uptake by cells was time-dependent, with a slow and sustained drug release from the lysosomes at a low pH. Also, when CHO (a normal cell) and MCF-7 (a cancer cell) were treated with NPDA, the results demonstrated that NPDA preferentially accumulated much more in tumor cells than in normal cells, which implied that NPDA has the ability to selectively kill tumor cells. In addition, NPDA can inhibit the migration and proliferation of tumor cells and change the cell cycle compared to the free drug. Outcomes from this work suggest that NPDA would be a promising drug delivery platform and the preparation of such a drug delivery system will also have implications in improving the biomedical applications of smart nanodiamond carriers.
authors: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, P. R. China. yangbs@sxu.edu.cn.
authors: Lin
authors: L
authors: Li
authors: Lu
authors: L
authors: Tian
authors: Wenjing
authors: W
authors: Zhao
authors: Yingqi
authors: Y
authors: Li
authors: Binsheng
authors: B
authors: Yang
mesh_terms: D065966:Absorption, Physicochemical; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004355:Drug Stability; D006801:Humans; D007477:Ions; D061986:MCF-7 Cells; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D058612:Nanodiamonds / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry*; D019346:Sodium Acetate / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D007477:Ions; D053769:Nanocapsules; D058612:Nanodiamonds; D011092:Polyethylene Glycols; D019346:Sodium Acetate; D004317:Doxorubicin