A pH-responsive complex based on supramolecular organic framework for drug-resistant breast cancer therapy

Abstract

Chemotherapy is one of the main ways to treat breast cancer clinically. However, the multidrug resistance to anti-tumor drugs limits their clinical use. To overcome these drawbacks, the development of drug delivery systems (DDSs) has attracted more and more attention in cancer therapy. At present, the preparation and purification process are complicated for many reported DDSs, while the clinic calls for new DDSs that are more convenient for preparation. Here a new pH-responsive supramolecular organic framework drug delivery complex loading doxorubicin (DOX) is fabricated. Anti-tumor activity of the system in vitro was investigated by cell cytotoxicity, uptake assay, and cell apoptosis analysis. The anti-tumor activity in vivo was investigated by inspecting nude mice body weight, tumor volume and weight, also a preliminary mechanism probe was conducted by HE and TUNEL staining. The DOX@SOF displayed high stability, good biocompatibility and pH-regulated drug release. At acid condition, the hydrazone bonds would be broken, which result in the dissociation of SOF, and then the drugs would be released from the system. Furthermore, DOX@SOF enhanced cellular internalization. Both in vitro and in vivo experiments reflected that DOX@SOF could enhance the anti-tumor activity of DOX. for the MCF-7/ADR tumor cells and tumors. This study provides a highly efficient strategy to prepare a stimulus-responsive supramolecular drug delivery complex for the treatment of drug-resistant cancer, the results presented inspiring scientific interests in exploring new drug delivery strategies and reversing multi-drug resistance for clinical chemotherapy.

Stimuli-Responsive Cucurbit[n]uril-Based Supramolecular Nanocarriers for Delivery of Chemotherapeutics

“…TAH and CB [8] mixture in water had provoked the encapsulation of CB [8] macrocycles for the intermolecular dimers that could be established by the attached aromatic arms of TAH. 16 physiological environment (pH 7.4), the dissociation half-life of the nanocomplexes could reach ∼32 h, with a stable kinetic profile in blood serum for ∼10 h (Figure 9). 1 Moreover, a significant improvement in the complexes cytotoxicity was reported at acidic pH of 6.5 as compared to pH 7.4.…”

“…Zhang et al (2022) designed a novel pH-triggered CB [8]based supramolecular nanosystem with a three-dimensional organic-framework structure loaded with DOX. 16 The nanocomplex system was constructed by the self-assembly of dispersed DOX and the supramolecular-organic-framework (CB[8]SOF) (DOX@CB[8]SOF). 16 The preparation of SOF was initiated by mixing 4,4′,4″,4‴-methanetetrayltetra-(benzohydrazide), 4-(1-methyl-pyridin-4-yl)benzaldehyde, and chloride salt in water.…”

Recent progress on the construction of supramolecular organic frameworks based on macrocyclic hosts

“…11). 138 When SOF-22 reaches the acidic tumor region, the hydrazone bond breaks and the SOF is dissociated, resulting in the release of the loaded doxorubicin (DOX). This stimuli-responsive supramolecular drug delivery system has been successfully applied to the treatment of drug-resistant cancer.…”

A novel strategy of constructing an artificial light-harvesting system based on a supramolecular organic framework for photocatalysis

“…Up to now, there are many reports on the application of SOFs, such as ion and explosive detection, 28–30 cell imaging, 5,20 visible-light-driven hydrogen evolution, 31,32 drug delivery, 33 and photodynamic therapy. 34,35 However, the application of SOFs still needs to be further expanded.…”