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

Guiyang Zhang,Xinle Li,Wenyu Huang,Yanfeng Liu,Kai Xi,Xudong Jia,Qiaobo Liao

doi:10.1038/s41467-018-04910-5

Guiyang Zhang, Xinle Li + Show 5 more

Open Access

https://doi.org/10.1038/s41467-018-04910-5

Copy DOI

Journal: Nature Communications	Publication Date: Jul 17, 2018
Citations: 370	License type: open-access

Affiliation: Nanjing University, Iowa State University

Abstract

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, PEG350-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.

Highlights

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
We develop a facile synthesis of a polymer-COF nanocomposite via the self-assembly of polyethylene-glycol-modified monofunctional curcumin derivatives (PEG-CCM) and amine-functionalized COF‐1 (APTES-COF-1)
The series of polyethylene glycol (PEG)-CCM composites were characterized by electrospray ionization mass spectrometry (ESI-MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDITOF MS)

Summary

Introduction

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. We develop a series of water-dispersible polymer-COF nanocomposites through the assembly of polyethylene-glycol-modified monofunctional curcumin derivatives (PEG-CCM) and aminefunctionalized COFs (APTES-COF-1) for in vitro and in vivo drug delivery. Monofunctional curcumin (CCM) derivatives modified by polyethylene glycol (PEG) hold three advantages: (a) the presence of free phenolic groups endows CCM with antioxidant biological activity[32]; (b) CCM could be used as a fluorescent label for tracking; and (c) using monofunctional derivatives to modify polymers could form soluble conjugates in high yields, while using bifunctional derivatives would result in cross-linked products with poor solubility[33] Taking these factors into consideration, we anticipate that the COF-polymer hybridization could open up a new route for the design of multifunctional nanocomposites for efficient and controllable drug delivery. To the best of our knowledge, this represents a rare example that introduces the emerging research of polymer-COF assembly for therapeutic applications

Methods

Results

Conclusion