CAIXplatins: Highly Potent Platinum(IV) Prodrugs Selective Against Carbonic Anhydrase IX for the Treatment of Hypoxic Tumors

Cao, Qian; Zhou, Dian-Yuan; Zhang, Pan; Yang, Ganggang; Zhang, Hang; Ji, Liang; Mao, Zong‐Wan

doi:10.1002/anie.202005362

Cited by 106 publications

(68 citation statements)

References 44 publications

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“…Due to this, these substances suppress tumor metabolic pathways, which results in increased therapeutic effects proven on MDA-MB-231 breast cancer cells in comparison to cisplatin and oxaliplatin. With the modification, significantly higher selectivity and cytotoxicity of the new drugs on cancer cells under hypoxia are observed [ 23 ].…”

Section: Modifications Of Platinum- and Palladium-based Moleculesmentioning

confidence: 99%

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments

Czarnomysy

Radomska

Szewczyk

et al. 2021

IJMS

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There is a need for new, safer, and more effective agents to treat cancer. Cytostatics that have transition metals at their core have attracted renewed interest from scientists. Researchers are attempting to use chemotherapeutics, such as cisplatin, in combination therapy (i.e., in order to enhance their effectiveness). Moreover, studies are being carried out to modify molecules, by developing them into multinuclear structures, linking different compounds to commonly used drugs, or encapsulating them in nanoparticles to improve pharmacokinetic parameters, and increase the selectivity of these drugs. Therefore, we attempted to organize recent drug findings that contain palladium and platinum atoms in their structures.

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Section: Modifications Of Platinum- and Palladium-based Moleculesmentioning

confidence: 99%

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments

Czarnomysy

Radomska

Szewczyk

et al. 2021

IJMS

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“…Our group also reported two novel platinum(IV) prodrugs against hypoxic tumors via CAIX targeting and intervention. However, which limits their further application in immunotherapy [18] . In contrast, as shown in Scheme 1, the CAIX anchoring feature endows our designed CA‐Re the ability to always fix on the cell membrane after long‐term culture (>24 h), even after light irradiation destroys the membrane integrity.…”

Section: Introductionmentioning

confidence: 92%

A Carbonic Anhydrase IX (CAIX)‐Anchored Rhenium(I) Photosensitizer Evokes Pyroptosis for Enhanced Anti‐Tumor Immunity

et al. 2021

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An ideal cancer treatment should not only destroy primary tumors but also improve the immunogenicity of the tumor microenvironment to achieve a satisfactory anti‐tumor immune effect. We designed a carbonic anhydrase IX (CAIX)‐anchored rhenium(I) photosensitizer, named CA‐Re, that not only performs type‐I and type‐II photodynamic therapy (PDT) with high efficiency under hypoxia (nanomolar‐level phototoxicity), but also evokes gasdermin D (GSDMD) mediated pyroptotic cell death to effectively stimulate tumor immunogenicity. CA‐Re could disrupt and self‐report the loss of membrane integrity simultaneously. This promoted the maturation and antigen‐presenting ability of dendritic cells (DCs), and fully activated T cells dependent adaptive immune response in vivo, eventually eliminating distant tumors at the same time as destroying primary tumors. To the best of our knowledge, CA‐Re is the first metal complex‐based pyroptosis inducer.

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“…Compared with Pt(II) anti-tumor drugs, Pt(IV) complexes are more stable due to their kinetic inertia. 101 Moreover, the two additional ligands introduced by the octahedral metal center provide many possibilities for improving pharmacokinetic parameters, including enhancing molecular targeting. 102 Since Pt(IV) must be reduced to Pt(II) in the cell to exhibit cytotoxicity, the Pt(IV)-based prodrug provides a better method for tumor-targeted delivery of cisplatin or its analogs.…”

Section: Metal Ion Therapeutic Strategy Based On Dna Damagementioning

confidence: 99%