Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle

Hou, Xiaoxue; Chang, Yuxuan; Yue, Yu‐Xin; Wang, Ze‐Han; Ding, Fei; Li, Zhihao; Li, Hua‐Bin; Xu, Yaohua; Kong, Xianglei; Huang, Fan; Guo, Dong‐Sheng; Liu, Jianfeng

doi:10.1002/advs.202104349

Cited by 34 publications

(21 citation statements)

References 69 publications

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“…We determined that the fluorescence intensity of NAQA⊂Zn-MPPB was considerable weak in untreated A549 and MCF- control), because of the relatively low content of intracellular NTR. In contrast, under the hypoxia conditions (8% and 0.1% O 2 ), an obvious fluorescence signal corresponding to NAQA⊂Zn-MPPB 54 was observed (Figure 4A). As the hypoxia degree increased, the effect of cell fluorescence imaging becomes more obvious, over 3-fold stronger fluorescence emission intensity of MCF-7 cells in 0.1% O 2 than under normoxic conditions (see Figure S43A in the Supporting Information).…”

Section: ■ Results and Discussionmentioning

confidence: 91%

Supramolecular Host–Guest Strategy for the Accelerating Detection of Nitroreductase

Zhang

Jiao

Yang

et al. 2023

ACS Appl. Mater. Interfaces

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Identifying nitroreductase (NTR) with fluorescent techniques has become a research hotspot, due to its good sensitivity and selectivity toward the early-stage cancer diagnosis and monitoring. Herein, a host−guest reporter (NAQA⊂Zn-MPPB) is successfully achieved by encapsulating the NTR probe NAQA into a new NADH-functioned metal−organic cage Zn-MPPB, which makes the reporter for ultrafast detection of NTR within dozens of seconds in solution. The host−guest strategy fuses the Zn-MPPB and NAQA to form a pseudomolecule material, which changes the reaction process of NTR and NAQA from a double substrates mechanism to a single substrate one, and accelerates the reduction efficiency of NAQA. This advantage make the new host−guest reporter exhibit a linear relationship between emission changes and NTR concentration, and it shows better sensitively toward NTR than that of NAQA. Additionally, the positively charged water-soluble metal−organic cage can encapsulate NAQA in the cavity, promote it to dissolve in an aqueous environment, and facilitate their accumulation into tumor cells. As expected, such host−guest reporter displays a fast and high efficiently imaging capability toward NTR in tumor cells and tumor-bearing mice, and flow cytometry assay is conducted to corroborate the capability as well, implying the considerably potential of host−guest strategy for early tumor diagnosis and treatment.

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Section: ■ Results and Discussionmentioning

confidence: 91%

Supramolecular Host–Guest Strategy for the Accelerating Detection of Nitroreductase

Zhang

Jiao

Yang

et al. 2023

ACS Appl. Mater. Interfaces

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“…6 ). Calixarenes were selected as the macrocyclic scaffold because of their extensive chemical design space 50 – 53 . By directly reacting calix[4]arene with p -carboxybenzenediazonium chloride at 2 °C for 3 h, CAC4A, which can be linked by condensation reaction with propargyl amine, getting CAC4A-Alk, was obtained with quantitative yield.…”

Section: Resultsmentioning

confidence: 99%

Lactose azocalixarene drug delivery system for the treatment of multidrug-resistant pseudomonas aeruginosa infected diabetic ulcer

et al. 2022

Nat Commun

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Diabetic wound is one of the most intractable chronic wounds that is prone to bacterial infection. Hypoxia is an important feature in its microenvironment. However, it is challenging for antimicrobial therapy to directly apply the existing hypoxia-responsive drug delivery systems due to the active targeting deficiency and the biofilm obstacle. Herein, we customizes a hypoxia-responsive carrier, lactose-modified azocalix[4]arene (LacAC4A) with the ability to actively target and inhibit biofilm. By loading ciprofloxacin (Cip), the resultant supramolecular nanoformulation Cip@LacAC4A demonstrates enhanced antibacterial efficacy resulting from both the increased drug accumulation and the controlled release at the site of infection. When applied on diabetic wounds together with multidrug-resistant Pseudomonas aeruginosa infection in vivo, Cip@LacAC4A induces definitely less inflammatory infiltration than free Cip, which translates into high wound healing performance. Importantly, such design principle provides a direction for developing antimicrobial drug delivery systems.

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“…Normal saline was purchased from Rhawn. SC5A, [ 36 ] SAC4A [ 37 ] and carboxylated azocalix[ n ]arenes (CAC n As, n = 4, 5, 6, 8) [ 38 ] were synthesized and purified according to literature procedures.…”

Section: Methodsmentioning

confidence: 99%

Promoting Tumor Accumulation of Anticancer Drugs by Hierarchical Carrying of Exogenous and Endogenous Vehicles

et al. 2022

Self Cite

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Cancer is still a major public health problem and a leading cause of death worldwide. [1] Currently, an increasing number of emerging therapeutic modalities, such as immunotherapy, gene therapy, photodynamic therapy, photothermal therapy, and chemodynamic therapy, have been developed in addition to traditional surgery, radiation, and chemotherapy. [2] In all drug treatments, the tumor accumulation of active pharmaceutical ingredients is a crucial parameter, as it is essential for the concentration of the drug to reach its therapeutic threshold rapidly to produce an effective response. [3] Numerous anticancer formulations have been widely studied and put into clinical practice to improve the tumor accumulation of drugs. Smallmolecular prodrugs are derivatives of active drugs, [4] which undergo biotransformation to release the parent drug by exploiting specific hallmarks of tumor microenvironments (e.g., pH, enzyme expression, reactive oxygen species) or by utilizing external triggers (e.g., light, ultrasound, magnetic energy). [5] Moreover, targeted drugs refer to a new generation of anticancer drugs designed to interfere with a specific molecular target (typically a protein), anticipated to have a critical role in tumor growth or progression. [6] To promote tumor accumulation, targeted drugs have gained importance, including small molecules (e.g., tyrosine kinase, mammalian target of rapamycin and proteasome inhibitors) and macromolecules (e.g., monoclonal antibodies, polypeptides, antibody-drug conjugates, and nucleic acids). [7] In recent decades, nanomedicine has gained ever-growing attention in fighting cancer. [8] Nanomedicine provides an alternate pathway to improve tumor accumulation relying on a wide range of targeting strategies such as active targeting, passive targeting (enhanced permeation and retention [EPR] effect), stimuliresponsive targeting and their combination. [9] Despite these significant achievements, the drawbacks of high tumor accumulation have not yet been addressed well. [3,10] Currently, only a few formulations (e.g., Abraxane, Lapatinib, Telotristat etiprate) (www.clinicaltrials.gov) have been clinically approved to modify the toxicological profile of drugs in patients. [11]

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Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle

Cited by 34 publications

References 69 publications

Supramolecular Host–Guest Strategy for the Accelerating Detection of Nitroreductase

Supramolecular Host–Guest Strategy for the Accelerating Detection of Nitroreductase

Lactose azocalixarene drug delivery system for the treatment of multidrug-resistant pseudomonas aeruginosa infected diabetic ulcer

Promoting Tumor Accumulation of Anticancer Drugs by Hierarchical Carrying of Exogenous and Endogenous Vehicles

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