title: A surface-grafted ligand functionalization strategy for coordinate binding of doxorubicin at surface of PEGylated mesoporous silica nanoparticles: Toward pH-responsive drug delivery.
abstract: To achieve drug targeting and on-demand releasing, surface functionalization plays a critical role in fabricating potential mesoporous silica nanoparticles (MSNs) toward tumor chemotherapy. Here, we prepared a size-controllable ligand-functionalized MSNs delivery system via coordinate bonding, which can release doxorubicin (DOX) in response to pH and prolong the circulation time of drug in vivo. After modifying the external surface of MSNs with polyethylene glycol (PEG), iminodiacetic acid (IDA) as a ligand was mainly grafted on the surface of mesopores to chelate cupric iron and DOX in sequence via coordinate bonds. The modified MSNs exhibited a uniform size of about 72nm and could be stably dispersed in saline. After DOX loading, the drug loading content and encapsulation efficiency were calculated to be 9.3±0.1% and 92.8±0.6%, respectively. Moreover, the resultant MSNs showed a pH-responsive release property, which could avoid the premature leakage of drug in circulation and achieve on-demand release within the tumor cells. Additionally, the pharmacokinetic study in healthy rats demonstrated that DOX loaded in functionalized MSNs presented the longer circulation time and lower plasma clearance rate compared with DOX solution. These results indicated that PEG/IDA modified MSNs with pH-responsive release capacity possessed great promising as an anticancer drug delivery system.
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address: zhtsing101@sina.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address: shuhudu@njmu.edu.cn.
authors.forename: Shuhu
authors.initials: S
authors.lastname: Du
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D007098:Imino Acids / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D007098:Imino Acids; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D004317:Doxorubicin; C008109:iminodiacetic acid
keywords: Coordinate bonds; Doxorubicin; Mesoporous silica nanoparticles; Targeting; pH-Response