Reticular Chemistry‐Enabled Sonodynamic Activity of Covalent Organic Frameworks for Nanodynamic Cancer Therapy

Abstract

The development of covalent organic framework (COF) sonosensitizers with intrinsic sonodynamic effects is highly desirable. However, such COFs are generally constructed using small‐molecule photosensitizers. Herein, we report that the reticular chemistry‐based synthesis of COFs from two inert monomers yields a COF‐based sonosensitizer (TPE‐NN) with inherent sonodynamic activity. Subsequently, a nanoscale COF TPE‐NN is fabricated and embedded with copper (Cu)‐coordinated sites to obtain TPE‐NN‐Cu. Results show that Cu coordination can enhance the sonodynamic effect of TPE‐NN, whereas ultrasound (US) irradiation for sonodynamic therapy can augment the chemodynamic efficacy of TPE‐NN‐Cu. Consequently, TPE‐NN‐Cu upon US irradiation shows high‐performance anticancer effects based on mutually reinforced sono‐/chemo‐nanodynamic therapy. This study reveals the backbone‐originated sonodynamic activity of COFs and proposes a paradigm of intrinsic COF sonosensitizers for nanodynamic therapy.

Strategies to engineer various nanocarrier-based hybrid catalysts for enhanced chemodynamic cancer therapy

“…COFs, a class of pure organic crystalline porous materials constructed by organic monomers with specific geometric shapes via dynamic covalent bonds, are emerging as a novel kind of nanocarriers for integrating various functional components, which has presented great potential for biomedical applications. To date, several examples of COF-based nanocatalysts for enhanced CDT have been reported by decorating metal ions (Cu 2+ , Fe 3+ , and Ni 2+ ) on the COFs’ monomers 105–107 or using the catalytically/therapeutically active monomers (such as ferrocene carboxaldehyde and Se–Se bonds-containing 4,4′-diselanedi-yldibenzaldehyde) as their building units. 108,109 This section focuses on the current status of research using COFs with intrinsic antitumor abilities as carriers of CDT agents.…”

“…Very recently, another paradigm that utilizes COF with intrinsic sonodynamic activity as a nanocarrier to carry Cu 2+ ions for nanodynamic cancer therapy was proposed by Duan and coworkers. 107 Instead of using photoactive porphyrin molecules as backbone units, they used two inactive monomers { i.e. , 4,4′,4′′,4′′′-(ethene-1,1,2,2-tetrayl) tetra-benzaldehyde (L-TPE) and N , N , N ′, N ′-tetrakis (4-amino-phenyl)-1,4-phenylenediamine (L-NN)} with no sonosensitization effects to synthesize an imine-linked COF (TPE-NN) with prominent sono-triggered ROS production capability, which was attributed to the reticular chemistry-enabled backbone formation (Fig.…”

Emerging porous solids and sonochemistry

“…Compared to conventional COF sonosensitizers composed of sonosensitizing organic building blocks, Zhang et al constructed the TPE-NN COF sonosensitizer from two inactive monomers 66 by reacting 4,4′,4′′,4′′′-(ethene-1,1,2,2-tetrayl)tetrabenzaldehyde and N , N , N′ , N′ -tetrakis(4-aminophenyl)-1,4-phenylenediamine in a mixture of o -dichlorobenzene, n -butanol, and 6 M aqueous acetic acid (Fig. 7e) at 120 °C for 72 h. In particular, while the monomers are incapable of generating ROS under US irradiation, TPE-NN effectively generates ROS owing to its extended π-conjugation and interlayer π–π interactions that afford a narrow bandgap that facilitates electron–hole separation promoted by US irradiation.…”

Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy

“…(A) Schematic diagram of post‐synthetic metalation of COFs. (B) Copper(II)‐coordinated TPE‐NN‐Cu for SDT and CDT [112] . (C) Iron(III)‐coordinated Fe‐TpPa‐COF for 808 nm laser‐excited PTT [113] …”