New Supramolecular Hypoxia-Sensitive Complexes Based on Azo-Thiacalixarene

Galieva, Farida; Khalifa, Mohamed; Akhmetzyanova, Z. V.; Mironova, Diana A.; Burilov, Vladimir; Solovieva, Svetlana E.; Антипин, И. С.

doi:10.3390/molecules28020466

Cited by 4 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, SAC5A can respond quickly under specific stimulus which is a prerequisite to achieving rapid and accurate unloading of drugs. To investigate the release kinetics of NMP-BE, rhodamine B (RhB) was employed as a model fluorescent probe encapsulated in SAC5A 63 , 64 . The binding affinity was determined to be 1.2 × 10 6 M −1 62 , which was in the same order of magnitude to that of NMP-BE@SAC5A ((5.1 ± 0.5) × 10 6 M −1 ).…”

Section: Resultsmentioning

confidence: 99%

Dual hypoxia-responsive supramolecular complex for cancer target therapy

Guo,

Li,

Wang

et al. 2023

Nat Commun

View full text Add to dashboard Cite

The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.

show abstract

Section: Resultsmentioning

confidence: 99%

Dual hypoxia-responsive supramolecular complex for cancer target therapy

Guo,

Li,

Wang

et al. 2023

Nat Commun

View full text Add to dashboard Cite

show abstract

“…An azocalixarene dimer (DSAC4A) was designed to construct a supramolecular polymer . Inspired by our work, other researchers also synthesized different azocalixarenes or modified azocalixarenes onto other materials like polymer or protein for application in sensing, bioimaging, and drug delivery. − …”

Section: Designing and Synthesizing Azocalixarenes As Hypoxia-respons...mentioning

confidence: 95%

Hypoxia-Responsive Host–Guest Drug Delivery System

Hu,

Fu,

Guo

2023

Acc. Mater. Res.

View full text Add to dashboard Cite

Conspectus A host–guest drug delivery system (HGDDS) refers to a host–guest complex of an artificial receptor and a therapeutic agent which can dissociate at the lesion site and release the loaded cargo. Macrocyclic receptors are promising drug carriers because of their superior properties, including ease of preparation, precise molecular weight, well-defined molecular structure, and excellent chemical stability. The host–guest loading process is mild, simple, and repeatable. The host–guest formulations can quantitatively load drug because of the exact cavity-loading pattern and quantifiable host–guest binding constant. Host–guest formulations are typically modular, which may be appealing in the context of personalized medicine because the macrocyclic carriers can act as a platform to complex diverse drugs. These lead to good batch reproductivity and excellent application prospects in both scientific research and industry. However, in order to make the HGDDS more suitable for practical application, several demands such as high binding affinity, universal binding to multiple drugs, targeting, and stimuli-responsiveness still need to be considered. The process of hypoxia is linked to several diseases and biological processes, including cancer, acute and chronic diseases, pathogenic microbe infection, and other stress responses. As part of our ongoing research on supramolecular biomaterials based on macrocycles by taking advantage of their recognition and assembly properties, we have developed a hypoxia-responsive HGDDS based on azocalixarenes. These azocalixarenes possess a deepened cavity, resulting in high binding affinities and high encapsulation efficiencies toward therapeutic agents. The azo group is one of the most frequently employed hypoxia-responsive moieties as it can be reduced under hypoxic microenvironments. This property confers the carriers with hypoxia-triggered release due to the remarkable decrease in binding affinities following reduction. The fast release kinetics further facilitates the efficient accumulation of drugs at the lesion site. These azocalixarene-based HGDDSs have been applied in preclinical studies for diagnosis and treatment of several diseases including tumor, bacterial infection, kidney injury, and rheumatoid arthritis. In this Account, we outline our recent efforts in designing and formulating HGDDSs based on azocalixarenes. We first provide a brief introduction of HGDDSs, including their features, the quantitative loading and ratiometric delivery models. Then the molecular design principles and synthesis methods, the strong binding affinity, the drug loading, and the fast hypoxia-response of azocalixarene-based HGDDSs are described. The applications of azocalixarene-based HGDDSs in treating different diseases are followed. Finally, despite the rapid development of azocalixarene-based HGDDSs, there are still several problems that need to be solved both scientifically and in terms of clinical translation. Therefore, we propose perspectives that can be further conducted on HGDDSs.

show abstract

“…Farida et al proposed a new hypoxia-sensitive fluorescent supramolecular complex 21@6G for hypoxia, 59 consisting of azophene-framed thiacalix [4]arene 21 with the common cationic rhodamine dye 6G (Fig. 13).…”

Section: Detection Of Hypoxiamentioning

confidence: 99%