Developing a Gallium(III) Agent Based on the Properties of the Tumor Microenvironment and Lactoferrin: Achieving Two-Agent Co-delivery and Multi-targeted Combination Therapy of Cancer

Yang, Tongfu; Zhang, Zhenlei; Zhang, Juzheng; Li, Yanping; Li, Wenjuan; Liang, Hong; Yang, Feng

doi:10.1021/acs.jmedchem.2c01684

Cited by 17 publications

(14 citation statements)

References 62 publications

(71 reference statements)

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“…Thiosemicarbazone compounds are not only promising anticancer agents but can also be easily coordinated with metals because they contain sulfur atoms and nitrogen atoms. − To obtain a Pt(II) thiosemicarbazone compound with remarkable cytotoxicity and low toxicity, we designed and synthesized a series of Pt(II) thiosemicarbazone compounds. The crystal structures of four Pt(II) compounds (C1–C4) were identified by X-ray crystallography (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Developing an Anticancer Platinum(II) Compound Based on the Uniqueness of Human Serum Albumin

Zhang

Yang

et al. 2023

J. Med. Chem.

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To develop the next-generation Pt drug with remarkable activity and low toxicity to maximally inhibit tumor growth, we optimized a Pt(II) thiosemicarbazone compound (C4) with remarkable cytotoxicity to SK-N-MC cells and then constructed a new human serum albumin−C4 (HSA− C4) complex delivery system. The in vivo results showed that C4 and the HSA−C4 complex have remarkable therapeutic efficiency and almost no toxicity; they induced apoptosis and inhibited tumor angiogenesis. This system showed potential as a practical Pt drug. This study could pave the way for developing next-generation dual-targeted Pt drugs and achieving their targeting therapy for cancer.

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Section: Resultsmentioning

confidence: 99%

Developing an Anticancer Platinum(II) Compound Based on the Uniqueness of Human Serum Albumin

Zhang

Yang

et al. 2023

J. Med. Chem.

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“…145,146 Recently, Yang et al showed that their gallium compound and its nanoparticle formulation upregulate CD86 and PD1, while downregulating expression of PD-L1 in tumor tissue. 147 Additional research on the effects of exposure to gallium arsenide (GaAs), a compound used in the production of semiconductors has shown that it can reduce CD4 + T-cell activation in mice. 148 However, the arsenide rather than the gallium appears to be the primary mediator of this effect.…”

Section: Impact Of Gallium Compounds On Pro-inflammatory Molecules An...mentioning

confidence: 99%

“…Investigations into the use of gallium compounds as therapeutic immunosuppressives have shown that Ga(NO 3 ) 3 can be used to effectively suppress lupus and prevent immune rejection of tissue grafts in mice. , Recently, Yang et al. showed that their gallium compound and its nanoparticle formulation upregulate CD86 and PD1, while downregulating expression of PD-L1 in tumor tissue …”

Section: In Vitro Antimicrobial Activity Of Gallium Compounds and Mec...mentioning

confidence: 99%

Development of Gallium(III) as an Antimicrobial Drug Targeting Pathophysiologic Iron Metabolism of Human Pathogens

et al. 2023

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The treatment of infections is becoming more difficult due to emerging resistance of pathogens to existing drugs. As such, alternative druggable targets, particularly those that are essential for microbe viability and thus make it harder to develop resistance, are desperately needed. In turn, once identified, safe and effective agents that disrupt these targets must be developed. Microbial acquisition and use of iron is a promising novel target for antimicrobial drug development. In this Review we look at the various facets of iron metabolism critical to human infection with pathogenic microbes and the various ways in which it can be targeted, altered, disrupted, and taken advantage of to halt or eliminate microbial infections. Although a variety of agents will be touched upon, the primary focus will be on the potential use of one or more gallium complexes as a new class of antimicrobial agents. In vitro and in vivo data on the activity of gallium complexes against a variety of pathogens including ESKAPE pathogens, mycobacteria, emerging viruses, and fungi will be discussed in detail, as well as pharmacokinetics, novel formulations and delivery approaches, and early human clinical results.

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“…Nanocarriers have been one of the most promising strategies to solve these problems . Protein-based nanocarriers have demonstrated great superiority over synthetic nanocarriers because of their low cytotoxicity, stability, biodegradability, and high biocompatibility. − Apoferritin (AFt), a ferritin without iron with a hollow sphere structure, and different drugs may be encapsulated into AFt nanocages. Therefore, AFt has emerged as a promising drug carrier in cancer therapy. − …”

Section: Introductionmentioning

confidence: 99%

Developing a Gadolinium(III) Compound Based on Apoferritin for Targeted Magnetic Resonance Imaging and Dual-Modal Therapy of Cancer

Man

Yang

et al. 2023

J. Med. Chem.

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To integrate targeted diagnosis and treatment of cancer, we proposed to develop a gadolinium (Gd) agent based on the properties of apoferritin (AFt). To this end, we not only optimized a series of Gd(III) 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazone compounds to obtain a Gd(III) compound (C4) with remarkable T 1 -weighted magnetic resonance imaging (MRI) performance and cytotoxicity to cancer cells in vitro but also constructed an AFt−C4 nanoparticle (NP) delivery system. Importantly, AFt−C4 NPs improved the targeting ability of C4 in vivo and showed enhanced MRI performance and tumor growth inhibition ratio relative to C4 alone. Furthermore, we confirmed that C4 and AFt−C4 NPs inhibited tumor growth through apoptosis, ferroptosis, and ferroptosis-induced immune response.

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Developing a Gallium(III) Agent Based on the Properties of the Tumor Microenvironment and Lactoferrin: Achieving Two-Agent Co-delivery and Multi-targeted Combination Therapy of Cancer

Cited by 17 publications

References 62 publications

Developing an Anticancer Platinum(II) Compound Based on the Uniqueness of Human Serum Albumin

Developing an Anticancer Platinum(II) Compound Based on the Uniqueness of Human Serum Albumin

Development of Gallium(III) as an Antimicrobial Drug Targeting Pathophysiologic Iron Metabolism of Human Pathogens

Developing a Gadolinium(III) Compound Based on Apoferritin for Targeted Magnetic Resonance Imaging and Dual-Modal Therapy of Cancer

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