Design of size uniform and controllable covalent organic framework nanoparticles for high-performance anticancer drug delivery

Abstract

Covalent organic frameworks (COFs) receive much attention in biomedicine because of their unique adsorption, optical and biological properties, as well as highly variable structures. However, preparation of nanosized COFs with uniform and controllable size is still a challenge. Herein, we develop a facile interfacial method to prepare the COF nanoparticles (COFNPs) with the uniform size of 30–50 nm from p-benzoquinone (BQ) and 4-[1,2,2-tris(4-aminophenyl)ethenyl]aniline (TPEA) by Michael addition. The TPEA-BQ COFNPs show positive zeta potential and effectively load the hydrophobic anticancer drug camptothecin (CPT) with the capacity of up to 127wt%, and remarkably improved the CPT dispersibility in water due to the retention of quinone structure. In vitro assay reveals CPT@ TPEA-BQ significantly reduced cell viability to 29% after 24 h incubation, much lower than that of free CPT (51%) at the same concentration of 10 μg mL−1. Further in vivo experiment confirms the high anticancer drug delivery performance of the designed TPEA-BQ COFNPs. After 20 days of injection treatment, the CPT loaded in TPEA-BQ COFNPs inhibits the tumor growth by 60%, much higher than that of free CPT group (23%). This work demonstrates the feasibility to design advanced drug delivery systems based on highly structure-tunable COF system.

Nanoparticle delivery of TFOs is a novel targeted therapy for HER2 amplified breast cancer

“…In addition, since polymer nano-particle has extremely small size and high surface energy, nano-particles can penetrate directly into the cell membrane when they have appropriate properties [ 23 – 25 ], resulting in a higher growth inhibitory effect of TFO@ZW-128 than that of naked TFO. Particle size and drug loading are essential indices to evaluate nano-particle quality [ 26 , 27 ]. The ZW-128 used in this study was homogeneous and spherical, with an average particle size of 128 nm comparable to similar studies.…”

The Cutting‐Edge Progress in Covalent Organic Framework‐Based Nanomedicine

“…[ 26 ] Smaller sized COFs exhibit a higher rate of cellular uptake, thereby enhancing the efficiency of drug delivery. [ 60 ] Furthermore, the smaller COFs demonstrate superior biocompatibility due to their higher metabolic efficiency within biological systems.…”

A panoramic perspective of recent progress in 2D and 3D covalent organic frameworks for drug delivery

“…Weng and co‐workers [ 137 ] were one of the first to report a facile interface design method to synthesize COF NPs through Michael's addition of p‐benzoquinone and 4‐[1,2,2‐tris(4‐aminophenyl) ethenyl] aniline. To evaluate the drug release profile of COF NPs, CPT was firstly loaded on it, and then in vitro drug release study was done at different pH environments.…”