A proapoptotic peptide conjugated to penetratin selectively inhibits tumor cell growth

Alves, Isabel D.; Carré, Manon; Montero, Marie-Pierre; Castano, Sabine; Lecomte, Sophie; Marquant, Rodrigue; Lécorché, Pascaline; Burlina, Fabienne; Schatz, Christophe; Sagan, Sandrine; Chassaing, Gérard; Braguer, Diane; Lavielle, Solange

doi:10.1016/j.bbamem.2014.04.025

Cited by 58 publications

(37 citation statements)

References 56 publications

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“…In such cases, the linker should be cleaved to permit release of the drug conjugated to the CPP. For this purpose, cleavable linkers, such as an acid-labile hydrazone bond [41] or a reductioncleavable disulfide bond [42], have been used. A peptidic bond that can be broken by protease may also be applied [43].…”

Section: Challenges To Cpp Use In Cancer Treatmentmentioning

confidence: 99%

Cell-penetrating peptides: strategies for anticancer treatment

Raucher

Ryu

2015

Trends in Molecular Medicine

200

159

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Section: Challenges To Cpp Use In Cancer Treatmentmentioning

confidence: 99%

Cell-penetrating peptides: strategies for anticancer treatment

Raucher

Ryu

2015

Trends in Molecular Medicine

200

159

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“…The infant SGF and SIF were prepared as ascribed in the studies of Liu et al, 29 and Dupont et al 30 with slight modification. The pH of SGF and SIF were adjusted to 3.0 and 7.4, respectively.…”

Section: Digestion Of Lf Liposomes Under Simulated Gastric and Small mentioning

confidence: 99%

Structural characterization and biological fate of lactoferrin‐loaded liposomes during simulated infant digestion

Tian

Han

et al. 2019

J Sci Food Agric

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BACKGROUND Limited information is concerned on the structure changes of liposomal delivery system under infant conditions. Positively charged lactoferrin (LF)‐loaded liposomes, with the entrapment efficiency (EE) of 52.3 ± 6.3%, were prepared from soybean‐derived phospholipids using a thin‐layer dispersion method. The structure changes and digestibility of LF‐loaded liposomes under infant conditions, including simulated gastric fluid (SGF) and simulated small intestinal fluid (SIF), were characterized in terms of the average particle size, zeta potential, turbidity, fourier transform infrared, transmission electron microscopy, lipolysis and protein hydrolysis. RESULTS This study showed that the functional groups, favorable membrane structure and the EE of liposomes were slightly changed as a function of time when the liposome digested under SGF conditions. However, the intact bilayer structures were damaged and the EE of LF‐loaded liposomes decreased to 28.5% after digestion in infant SIF. CONCLUSION These results suggested that liposomal membrane could prevent the gastric degradation and the structure of liposomes was not completely destroyed with a low concentration of pancreatin and bile salts under infant conditions. Present study provided information on the insight into the characteristics of liposomes during infant gastrointestinal digestion, which was useful for the development of microcapsule systems in infant diet. © 2018 Society of Chemical Industry

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“…Another study showed that the proapoptotic peptide (KLAKLAK) 2 conjugated to penetratin led to selective inhibition of tumor cell growth. [55] To promote delivery of (KLAKLAK) 2 specifically to the GBM cells, we generated a recombinant protein IL-13-D2-KK2, which targets IL-13RA2. After biotin conjugation and detection with streptavidin, we showed that IL-13-D2-KK2 was effectively internalized into the GBM cells and co-localized with ATP-synthase.…”

Section: Discussionmentioning

confidence: 99%

Novel molecular multilevel targeted antitumor agents

et al. 2017

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A multifunctional fusion protein, IL-13.E13K-D2-NLS, effectively recognizes glioblastoma (GBM) cells and delivers its portion to the cell nucleus. IL-13.E13K-D2-NLS is composed of a cancer cell targeting ligand (IL-13.E13K), specialized cytosol translocation bacterial toxin domain 2 of Pseudomonas exotoxin A (D2) and SV40 T antigen nuclear localization signal (NLS). We have now tested whether we can produce proteins that would serve as a delivery vehicle to lysosomes and mitochondria as well. Moreover, we examined whether IL-13.E13K-D2-NLS can deliver anti-cancer drugs like doxorubicin to their nuclear site of action in cancer cells. We have thus constructed two novel proteins: IL-13.E13K-D2-LLS which incorporates lysosomal localization signal (LLS) of a human lysosomal associated membrane protein (LAMP-1) for targeting to lysosomes and IL-13-D2-KK2, which incorporates a pro-apoptotic peptide (KLAKLAK)2 (KK2) exerting its action in mitochondria. Furthermore, we have produced IL-13.E13K-D2-NLS and IL-13.E13K-D2-LLS versions containing a cysteine for site-specific conjugation with a modified doxorubicin, WP936. We found that single-chain recombinant proteins IL-13.E13K-D2-LLS and IL-13-D2-KK2 are internalized and localized mostly to the lysosomal and mitochondrial compartments, respectively, without major trafficking to cells’ nuclei. We also determined that IL-13.E13K-D2-NLS-cys[WP936], IL-13.E13K-D2-LAMP-cys[WP936] and IL-13-D2-KK2 were cytotoxic to GBM cells overexpressing IL-13RA2, while much less cytotoxic to GBM cell lines expressing low levels of the receptor. IL-13.E13K-D2-NLS-cys[WP936] was the most potent of the tested anti-tumor agents including free WP936. We believe that our receptor-directed intracellular organelle-targeted proteins can be employed for numerous specific and safer treatment applications when drugs have specific intracellular sites of their action.

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A proapoptotic peptide conjugated to penetratin selectively inhibits tumor cell growth

Cited by 58 publications

References 56 publications

Cell-penetrating peptides: strategies for anticancer treatment

Cell-penetrating peptides: strategies for anticancer treatment

Structural characterization and biological fate of lactoferrin‐loaded liposomes during simulated infant digestion

Novel molecular multilevel targeted antitumor agents

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