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

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.

Facile Fabrication of Redox‐Responsive Covalent Organic Framework Nanocarriers for Efficiently Loading and Delivering Doxorubicin

“…In addition, their unique photoelectric properties enable COFs to serve as a promising platform for photodynamic and photothermal therapy . However, some intrinsic limitations of COFs, such as intricate and tedious preparation process of building blocks, irregular shape and size as well as uncontrolled drug release, severely restrain their practical applications in drug delivery …”

Covalent Organic Frameworks (COFs) for Cancer Therapeutics

“…In 2018, Jia et al. reported water‐dispersible polyethylene glycol (PEG)‐coated COF‐1 as a smart carrier for in vivo drug delivery . As shown in Figure B, COF‐based nanocomposite PEG‐CCM@APTES‐COF‐1@DOX was synthesized by the self‐assembly of curcumin‐modified PEG (PEG‐CCM) and DOX‐loaded amine‐functionalized COF‐1 (APTES‐COF‐1@DOX).…”

Regenerable and stable sp2 carbon-conjugated covalent organic frameworks for selective detection and extraction of uranium

“…At present, various COFs based on the Schiff base reaction (for example, COF-TpAb-AO 1 , and o-TDCOF 3 ) have been developed for the extraction of UO 2 2+ . However, their major covalent bonds, such as the boron-oxygen and imine bonds, are susceptible to irradiation, acid, and base, which greatly limit their regeneration and practical application 3,31,32 .…”