Design of Calixarene‐Based ICD Inducer for Efficient Cancer Immunotherapy

Zhang, Zhanzhan; Yue, Yu‐Xin; Li, Qiushi; Wang, Ying; Wu, Xueyao; Xue, L.; Li, Hua‐Bin; Shi, Linqi; Guo, Dong‐Sheng; Liu, Yang

doi:10.1002/adfm.202213967

Cited by 31 publications

(20 citation statements)

References 49 publications

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“…By training models on large data sets of known azocalixarene structures and their corresponding properties like binding affinities and hypoxia responsive kinetics, machine learning can aid in discovering novel azocalixarene derivatives with desired characteristics. Azocalixarenes can cooperate with other biomaterials in a covalent or noncovalent way, for instance, polymers, peptides, and proteins. ,,, Some living biomaterials such as living cells, bacteria, and cell/bacteria-derived biofilms can also be taken into consideration, which will harness the advantages of different materials and can be better used in biomedicine. Azocalixarenes have therapeutic activities. For example, QAAC4A can induce immunogenic cell death efficiently . By combining therapeutic activities with delivery capabilities, multifunctional integrated materials can be designed to aid in the treatment of complex diseases. Compared to the macrocycles already available on the market as excipients, such as CDs and their derivates like sulfobutyl ether-β-CD and hydroxypropyl-β-CD, azocalixarenes showed stronger binding affinities toward various drugs.…”

Section: Discussionmentioning

confidence: 99%

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Hypoxia-Responsive Host–Guest Drug Delivery System

Hu,

Fu,

Guo

2023

Acc. Mater. Res.

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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.

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Section: Discussionmentioning

confidence: 99%

“…Azocalixarenes have therapeutic activities. For example, QAAC4A can induce immunogenic cell death efficiently . By combining therapeutic activities with delivery capabilities, multifunctional integrated materials can be designed to aid in the treatment of complex diseases.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Responsive Host–Guest Drug Delivery System

Hu,

Fu,

Guo

2023

Acc. Mater. Res.

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“…The rapid hypoxia-responsive drug release is one of the factors that enhance drug accumulation at the lesion site . Moreover, AzoCAs are universal platforms adaptable to various drugs, including chemotherapeutics, photothermal therapy and radiotherapy agents, and antibiotics, and they have been employed in treating several diseases, including cancer, bacterial infections, kidney injuries, and rheumatoid arthritis. ,− It should be noted that although AzoCAs are appliable as drug carriers for all diseases with a hypoxic microenvironment in principle, we still need to decorate the target or other functional groups according to the characteristics of a certain disease to achieve better delivery and therapeutic efficacies . Herein, we only briefly introduce the tumor-related applications due to space limitations.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Molecular Recognition with Macrocyclic Receptors for Application in Precision Medicine

Pan,

Tian,

Guo

2023

Acc. Chem. Res.

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“…38 CAs are a class of widely adaptable macrocyclic hosts due to their size-tunable cavities, and are acknowledged to be the third generation of macrocyclic hosts after crown ethers and cyclodextrins. [39][40][41][42] Pillararenes (PAs) are some of the most well-known macrocyclic arenes, first introduced by Ogoshi and co-workers in 2008. 43 PAs possess rigid pillar-shaped structures, which are generally connected by hydroquinone units with methylene bridges at the para positions.…”

Section: Introductionmentioning

confidence: 99%