Legumain/pH dual-responsive lytic peptide–paclitaxel conjugate for synergistic cancer therapy

Zheng, Shourong; Cai, Yue; Hong, Yulu; Gong, Yubei; Gao, Licheng; Li, Qingyong; Li, Le; Sun, Xuanrong

doi:10.1080/10717544.2022.2081380

Cited by 9 publications

(1 citation statement)

References 42 publications

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“…Recently, a lytic peptide conjugated to paclitaxel was shown to have a dual and synergistic cytotoxic effect after cleavage by legumain in the tumor [158]. The first legumainbased DNA vaccine was developed in 2006 and was shown to induce a marked CD8+ T cell response by reducing tumor TAMs density and their release of proangiogenic factors, and subsequently the suppression of tumor growth, angiogenesis, and metastasis [143].…”

Section: Role Of Legumain In Cancermentioning

confidence: 99%

The Mammalian Cysteine Protease Legumain in Health and Disease

Solberg

Lunde

Forbord

et al. 2022

IJMS

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The cysteine protease legumain (also known as asparaginyl endopeptidase or δ-secretase) is the only known mammalian asparaginyl endopeptidase and is primarily localized to the endolysosomal system, although it is also found extracellularly as a secreted protein. Legumain is involved in the regulation of diverse biological processes and tissue homeostasis, and in the pathogenesis of various malignant and nonmalignant diseases. In addition to its proteolytic activity that leads to the degradation or activation of different substrates, legumain has also been shown to have a nonproteolytic ligase function. This review summarizes the current knowledge about legumain functions in health and disease, including kidney homeostasis, hematopoietic homeostasis, bone remodeling, cardiovascular and cerebrovascular diseases, fibrosis, aging and senescence, neurodegenerative diseases and cancer. In addition, this review addresses the effects of some marketed drugs on legumain. Expanding our knowledge on legumain will delineate the importance of this enzyme in regulating physiological processes and disease conditions.

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Section: Role Of Legumain In Cancermentioning

confidence: 99%

The Mammalian Cysteine Protease Legumain in Health and Disease

Solberg

Lunde

Forbord

et al. 2022

IJMS

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Reduction‐Responsive RGD‐Docetaxel Conjugate: Synthesis, In Vitro Drug Release and In Vitro Antitumor Activity

Li,

Liu,

Cheng

et al. 2024

Drug Development Research

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Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug docetaxel (DTX). Peptide–drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor‐selective drug delivery. In the present research, DTX is condensed with 3‐(pyridin‐2‐yldisulfanyl) propanoic acid via ester bond to obtain the intermediate Py‐SS‐DTX. Two conjugates GSS‐DTX and RGDC‐SS‐DTX were obtained by conjugation of Py‐SS‐DTX with glutathione (GSH) and RGDC peptide through a thiol‐disulfide exchange reaction. Afterwards, these two peptide–DTX conjugates were characterized by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high‐resolution mass spectrometry. The GSS‐DTX and RGDC‐SS‐DTX were further evaluated in terms of drug release, cell cycle inhibition, cell apoptosis, and cytotoxicity. The results show that both the GSS‐DTX and RGDC‐SS‐DTX exhibit reduction‐responsive drug release and RGDC‐SS‐DTX exhibit higher reduction‐responsiveness. The in vitro antitumor activity study shows that RGDC‐SS‐DTX exhibits enhanced G2/M phase arrest, cell apoptosis rate, and cytotoxicity as compared to GSS‐DTX and free DTX. Besides, RGDC‐SS‐DTX shows reduced cytotoxicity on normal cells as compared to free DTX. The RGDC‐SS‐DTX synthesized in this study represents a novel DTX conjugate to effectively and selectively inhibit tumor cells.

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Use of stimulatory responsive soft nanoparticles for intracellular drug delivery

et al. 2023

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Drug delivery has made tremendous advances in the last decade. Targeted therapies are increasingly common, with intracellular delivery highly impactful and sought after. Intracellular drug delivery systems have limitations due to imprecise and non-targeted release profiles. One way this can be addressed is through using stimuli-responsive soft nanoparticles, which contain materials with an organic backbone such as lipids and polymers. The choice of biomaterial is essential for soft nanoparticles to be responsive to internal or external stimuli. The nanoparticle must retain its integrity and payload in non-targeted physiological conditions while responding to particular intracellular environments where payload release is desired. Multiple internal and external factors could stimulate the intracellular release of drugs from nanoparticles. Internal stimuli include pH, oxidation, and enzymes, while external stimuli include ultrasound, light, electricity, and magnetic fields. Stimulatory responsive soft nanoparticulate systems specifically utilized to modulate intracellular delivery of drugs are explored in this review.

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Legumain/pH dual-responsive lytic peptide–paclitaxel conjugate for synergistic cancer therapy

Cited by 9 publications

References 42 publications

The Mammalian Cysteine Protease Legumain in Health and Disease

The Mammalian Cysteine Protease Legumain in Health and Disease

Reduction‐Responsive RGD‐Docetaxel Conjugate: Synthesis, In Vitro Drug Release and In Vitro Antitumor Activity

Use of stimulatory responsive soft nanoparticles for intracellular drug delivery

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