A naphthalimide-polyamine conjugate preferentially accumulates in hepatic carcinoma metastases as a lysosome-targeted antimetastatic agent

Ma, Jing; Li, Linrong; Yue, Kexin; Zhang, Zhansheng; Su, Shihao; Chen, Yutong; Lu, Yu; Zhang, Pengfei; Ma, Rui-juan; Li, Yingguang; Ma, Yinxia; Jia, Huinan; Wang, Chaojie; Wang, Jiajia; Xie, Songqiang

doi:10.1016/j.ejmech.2021.113469

Cited by 15 publications

(15 citation statements)

References 22 publications

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“…The strategy of incorporation of various carbohydrate moieties, including galactose, sialic acid, and glucose into natural products or peptides, has been proved to be an effective strategy to improve the bio-availability and anti-tumor activity ( Pohl et al, 1995 ; Moradi et al, 2016 ; Kabotso et al, 2020 ). Moreover, our group has previously reported a series of drugs based on the naphthalimide structures, which was notorious for poor water solubility, although it was widely used as a drug design and fluorescent probe ( Ma et al, 2020 ; Ma et al, 2021 ). Hydrogen sulfide, an important signaling molecule in living organisms, exerts multiple regulatory functions, such as stimulating vasodilation and maintaining redox homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Selective synthesis of α- and β-glycosides of N-acetyl galactosamine using rare earth metal triflates

Wang

Zhang²,

Cao³

et al. 2022

Front. Chem.

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Structures containing galactose and GalNAc residues are specifically recognized by asialoglycoprotein receptors, allowing them to selectively internalize by hepatocytes for drug-targeting delivery. However, methods for direct synthesis of GalNAc glycosides are still challenging due to the poor participating group of 2-acetamido. Here, we develop a facile strategy to synthesize various GalNAc glycosides by employing a series of rare earth metal triflates, and the results demonstrate that both α-glycosides and β-glycosides of GalNAc can be obtained by conducting with Hf(OTf)4 and Sc(OTf)3, respectively. These applicable results indicate that any interested GalNAc-containing substrates could be prepared by this simple strategy.

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Section: Resultsmentioning

confidence: 99%

Selective synthesis of α- and β-glycosides of N-acetyl galactosamine using rare earth metal triflates

Wang

Zhang²,

Cao³

et al. 2022

Front. Chem.

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“…The naphthalene lactam intermediates 10a-10c and 16a-16b in Fig. S1 and Scheme S6 were prepared as previously reported by our group [18][19][20][21][22][23]28] . The purity of final platinum complexes was confirmed to be ≥ 95% by analytical HPLC (Tables S1 and S2).…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

“…Blockade of BRAFi-induced transcriptional activation of lysosomal function causes metastatic dissemination and chemoresistance, which is associated with enhanced TGF-β signaling pathway [17] . Consequently, altering the lysosomal metabolismmeditated TGF-β pathway is a major challenge and a potential breakthrough in the development of chemotherapeutic candidates in anti-TNBC therapies and Treg biology-related antineoplastic protocols have not been reported by our group [18][19][20][21][22][23] or others [15] .…”

Section: Introductionmentioning

confidence: 99%

Suppression of lysosome metabolism-meditated GARP/TGF-β1 complexes specifically depletes regulatory T cells to inhibit breast cancer metastasis

Chen¹,

Li²,

Liu³

et al. 2023

Preprint

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Regulatory T cells (Tregs) prevent autoimmunity and contribute to cancer progression. They exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-β1 (TGF-β1). However, the absence of a specific surface marker makes inhibiting the production of active TGF-β1 to specifically deplete human Tregs but not other cell types a challenge. TGF-β1 in an inactive form binds to Tregs membrane protein GARP and then activates it via an unknown mechanism. Here, we demonstrate that TRAF3IP3 in the Treg lysosome is involved in this activation mechanism. Using a novel naphthalenelactam-platinum-based anticancer drug (NPt), we developed a new synergistic effect by suppressing ABCB9 and TRAF3IP3-mediated divergent lysosomal metabolic programs in tumors and human Tregs to block the production of active GARP/TGF-β1 for remodeling the tumor microenvironment. Mechanistically, NPt is stored in Treg lysosome to inhibit TRAF3IP3-meditated GARP/TGF-β1 complex activation to specifically deplete Tregs. In addition, by promoting the expression of ABCB9 in lysosome membrane, NPt inhibits SARA/p-SMAD2/3 through CHRD-induced TGF-β1 signaling pathway. In addition to expose a previously undefined divergent lysosomal metabolic program-meditated GARP/TGF-β1 complex blockade by exploring the inherent metabolic plasticity, NPt may serve as a therapeutic tool to boost unrecognized Treg-based immune responses to infection or cancer via a mechanism distinct from traditional platinum drugs and currently available immune-modulatory antibodies.

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“…Some naphthalimide-polyamine conjugates significantly inhibited tumor growth and metastasis [ 74 , 75 , 76 ]. Xie’s group [ 74 ] designed and synthesized a series of naphthalimide-polyamine conjugates ( 12a – 12d , 13a – 13c, and 14a – 14b ). They found that compound 13b exhibited stronger antitumor activity against hepatoma cells than the other compounds.…”

Section: Tumor Polyamine-suppressing Strategymentioning

confidence: 99%

“… Chemical structures of the naphthalimide-polyamine conjugates, 12a – d , 13a – c and 14a – b [ 74 ]. …”

Section: Figures Scheme and Tablementioning

confidence: 99%

Recent Advances in Fluorescent Methods for Polyamine Detection and the Polyamine Suppressing Strategy in Tumor Treatment

Wang

Ran

et al. 2022

Biosensors

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The biogenic aliphatic polyamines (spermine, spermidine, and putrescine) are responsible for numerous cell functions, including cell proliferation, the stabilization of nucleic acid conformations, cell division, homeostasis, gene expression, and protein synthesis in living organisms. The change of polyamine concentrations in the urine or blood is usually related to the presence of malignant tumors and is regarded as a biomarker for the early diagnosis of cancer. Therefore, the detection of polyamine levels in physiological fluids can provide valuable information in terms of cancer diagnosis and in monitoring therapeutic effects. In this review, we summarize the recent advances in fluorescent methods for polyamine detection (supramolecular fluorescent sensing systems, fluorescent probes based on the chromophore reaction, fluorescent small molecules, and fluorescent nanoparticles). In addition, tumor polyamine-suppressing strategies (such as polyamine conjugate, polyamine analogs, combinations that target multiple components, spermine-responsive supramolecular chemotherapy, a combination of polyamine consumption and photodynamic therapy, etc.) are highlighted. We hope that this review promotes the development of more efficient polyamine detection methods and provides a comprehensive understanding of polyamine-based tumor suppressor strategies.

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A naphthalimide-polyamine conjugate preferentially accumulates in hepatic carcinoma metastases as a lysosome-targeted antimetastatic agent

Cited by 15 publications

References 22 publications

Selective synthesis of α- and β-glycosides of N-acetyl galactosamine using rare earth metal triflates

Selective synthesis of α- and β-glycosides of N-acetyl galactosamine using rare earth metal triflates

Suppression of lysosome metabolism-meditated GARP/TGF-β1 complexes specifically depletes regulatory T cells to inhibit breast cancer metastasis

Recent Advances in Fluorescent Methods for Polyamine Detection and the Polyamine Suppressing Strategy in Tumor Treatment

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