Hollow-structured covalent organic framework decorated with FA-PEG: A biocompatible nanocarrier for targeted and pH-responsive release of doxorubicin

Hollow nanostructures hold great promise for drug delivery applications due to their considerable capabilities for efficient drug encapsulation alongside distinct physicochemical attributes. Herein, an imine-linked hollow nanosphere covalent organic framework (COF) with high surface area and well-structured porosity was developed serving as a versatile drug delivery system (DDS) to achieve targeted and effective delivery of doxorubicin (DOX) as a chemotherapeutic agent. The production of COF hollow nanoparticles included the use of a heterogeneous nucleation and growth method, followed by the subsequent encapsulation of DOX. Following this, the nanoparticles underwent functionalization with folate-poly (ethylene glycol)-amine (FA-PEG) using a bonding defect strategy. An in vitro cytotoxicity assay and flow cytometry study against FR-negative HEK293 and FR-positive MCF7 cells were performed, revealing that FA-PEG-functionalized HCOF exhibited a unique targeting effect on cancer cells, surpassing the impact of DOX@HCOF on FR-positive MCF7 cancer cells. Additionally, the hollow architecture of the COF is engineered to undergo disintegration selectively under conditions of cancer cell pH, facilitating the comprehensive release of DOX. The pH-responsive and tumor-targeted attributes of the DOX@HCOF-PEG-FA open new avenues for incorporating structural engineered HCOFs as a promising drug carrier capable of regulating drug release and augmenting therapeutic efficacy.