title: Strategy for chemotherapeutic delivery using a nanosized porous metal-organic framework with a central composite design.
abstract: BACKGROUND
  Enhancing drug delivery is an ongoing endeavor in pharmaceutics, especially when the efficacy of chemotherapy for cancer is concerned. In this study, we prepared and evaluated nanosized HKUST-1 (nanoHKUST-1), nanosized metal-organic drug delivery framework, loaded with 5-fluorouracil (5-FU) for potential use in cancer treatment.
  
  
  METHODS
  NanoHKUST-1 was prepared by reacting copper (II) acetate [Cu(OAc)2] and benzene-1,3,5-tricarboxylic acid (H3BTC) with benzoic acid (C6H5COOH) at room temperature (23.7°C±2.4°C). A central composite design was used to optimize 5-FU-loaded nanoHKUST-1. Contact time, ethanol concentration, and 5-FU:material ratios were the independent variables, and the entrapment efficiency of 5-FU was the response parameter measured. Powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption were used to determine the morphology of nanoHKUST-1. In addition, 5-FU release studies were conducted, and the in vitro cytotoxicity was evaluated.
  
  
  RESULTS
  Entrapment efficiency and drug loading were 9.96% and 40.22%, respectively, while the small-angle X-ray diffraction patterns confirmed a regular porous structure. The SEM and TEM images of the nanoHKUST-1 confirmed the presence of round particles (diameter: approximately 100 nm) and regular polygon arrays of mesoporous channels of approximately 2-5 nm. The half-maximal lethal concentration (LC50) of the 5-FU-loaded nanoHKUST-1 was approximately 10 µg/mL.
  
  
  CONCLUSIONS
  The results indicated that nanoHKUST-1 is a potential vector worth developing as a cancer chemotherapeutic drug delivery system.
authors.affiliation: College of Pharmacy, Tianjin University of Traditional Chinese Medicine, Tianjin.
authors.forename: Yingpeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Guan
authors.affiliation: College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Chunjing
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Dong
authors.affiliation: College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Bai
authors.affiliation: Pope John XXIII High School, Everett, MA, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D000073396:Metal-Organic Frameworks; D008670:Metals; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D016062:Porosity; D014961:X-Ray Diffraction
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D000073396:Metal-Organic Frameworks; D008670:Metals; D009942:Organometallic Compounds; C539834:bis(1,3,5-benzenetricarboxylate)tricopper(II); D005472:Fluorouracil
keywords: 5-fluorouracil; drug delivery; nano-MOFs; nanoparticles