Water-dispersible PEG-curcumin/amine-functionalized covalent organic framework nanocomposites as smart carriers for in vivo drug delivery

• Published in: Nature communications Vol. 9; no. 1; pp. 2785 - 11
• Main Authors: Zhang, Guiyang, Li, Xinle, Liao, Qiaobo, Liu, Yanfeng, Xi, Kai, Huang, Wenyu, Jia, Xudong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.07.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 101/58; 13/31; 14/19; 631/45/2783; 639/301/54/152; 639/638/542/967; 64/60; Amines - chemistry; Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Biodegradability; Biodegradation; Brain; Cancer; Curcumin; Curcumin - chemistry; Dispersion; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers; Drug Compounding; Drug delivery; Drug delivery systems; Female; Fluorescence; HeLa Cells; Humanities and Social Sciences; Humans; In vivo methods and tests; Injections, Intravenous; Metal-Organic Frameworks - chemistry; Mice; Mice, Nude; multidisciplinary; Nanocomposites; Nanocomposites - administration & dosage; Nanocomposites - chemistry; Optical Imaging; Polyethylene glycol; Polyethylene Glycols - chemistry; Polyethylenes; Polymers; Propylamines - chemistry; Science; Science (multidisciplinary); Silanes - chemistry; Tumors; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - therapy; Water - chemistry; Xenograft Model Antitumor Assays
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04910-5

Covalent organic frameworks (COFs) as drug-delivery carriers have been mostly evaluated in vitro due to the lack of COFs nanocarriers that are suitable for in vivo studies. Here we develop a series of water-dispersible polymer-COF nanocomposites through the assembly of polyethylene-glycol-modified monofunctional curcumin derivatives (PEG-CCM) and amine-functionalized COFs (APTES-COF-1) for in vitro and in vivo drug delivery. The real-time fluorescence response shows efficient tracking of the COF-based materials upon cellular uptake and anticancer drug (doxorubicin (DOX)) release. Notably, in vitro and in vivo studies demonstrate that PEG-CCM@APTES-COF-1 is a smart carrier for drug delivery with superior stability, intrinsic biodegradability, high DOX loading capacity, strong and stable fluorescence, prolonged circulation time and improved drug accumulation in tumors. More intriguingly, PEG 350 -CCM@APTES-COF-1 presents an effective targeting strategy for brain research. We envisage that PEG-CCM@APTES-COF-1 nanocomposites represent a great promise toward the development of a multifunctional platform for cancer-targeted in vivo drug delivery. Despite their potential application as drug-delivery carriers, covalent organic frameworks (COF) have been only evaluated in vitro. Here the authors show by real time tracking in vivo the cell uptake of anticancer-drug loaded and water dispersible COFs.