Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor <i>in vitro</i> and <i>in vivo</i>

Li, Huipeng; Yuan, Dongfen; Sun, Minjie; Ping, Qineng

doi:10.1080/10717544.2016.1209797

Cited by 20 publications

(9 citation statements)

References 48 publications

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“…Various amounts of M-CTX-Fc such as 5, 10, 15 or 20 nmol conjugated to liposome encapsulating doxorubicin was prepared, respectively. The mean particle size of these liposomes was almost 150 nm, which was not significantly affected by the amount of ligand as previously described [ 27 , 28 ]. The optimal amount of M-CTX-Fc conjugated to liposomes was determined by the IC 50 ( Figure 4 B).…”

Section: Resultssupporting

confidence: 65%

Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein

Mahmud

Kasai

Khayrani

et al. 2018

IJMS

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We recently have established a successful xenograft model of human glioblastoma cells by enriching hyaluronic acid-dependent spheroid-forming populations termed U251MG-P1 cells from U251MG cells. Since U251MG-P1 cells have been confirmed to express CD44 along with principal stemness marker genes, OCT3/4, SOX2, KLF4 and Nanog, this CD44 expressing population appeared to majorly consist of undifferentiated cells. Evaluating the sensitivity to anti-cancer agents, we found U251MG-P1 cells were sensitive to doxorubicin with IC50 at 200 nM. Although doxorubicin has serious side-effects, establishment of an efficient therapy targeting undifferentiated glioblastoma cell population is necessary. We previously designed a chlorotoxin peptide fused to human IgG Fc region without hinge sequence (M-CTX-Fc), which exhibited a stronger growth inhibitory effect on the glioblastoma cell line A172 than an original chlorotoxin peptide. Combining these results together, we designed M-CTX-Fc conjugated liposomes encapsulating doxorubicin and used U251MG-P1 cells as the target model in this study. The liposome modified with M-CTX-Fc was designed with a diameter of approximately 100–150 nm and showed high encapsulation efficiency, adequate loading capacity of anticancer drug, enhanced antitumor effects demonstrating increasing uptake into the cells in vitro; M-CTX-Fc-L-Dox shows great promise in its ability to suppress tumor growth in vivo and it could serve as a template for targeted delivery of other therapeutics.

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Section: Resultssupporting

confidence: 65%

Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein

Mahmud

Kasai

Khayrani

et al. 2018

IJMS

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“…On the other hands, liposomes have the disadvantage of being not specific to cancer cells and to vehiculate AMPs into mitochondrial membranes of normal cells causing damaging. Only if liposomes are tagged with ligands specific to tumor cells they may become safe for human in vivo testing [ 69 ].…”

Section: Critical Issues Possible Solutions For Clinical Use Of Amentioning

confidence: 99%

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

et al. 2020

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Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.

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“…An AMP delivered inside a eukaryotic cell will probably interact with mitochondria as it would with a bacterial cell, based on similarities between a bacterial cell and mitochondrial membranes. One strategy that is already developed is to tag the lysosome with a cancer cell-specific ligand for targeted delivery of the peptide [188]. Finally, designing AMPs as part of nanoparticles for delivery is another strategy that may improve PK properties of AMPs and should be explored [189–191].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications

2017

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In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs.

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Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor in vitro and in vivo

Cited by 20 publications

References 48 publications

Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein

Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications

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