F3 peptide-functionalized PEG-PLA nanoparticles co-administrated with tLyp-1 peptide for anti-glioma drug delivery

Hu, Quanyin; Gu, Guangzhi; Liu, Zhongyang; Jiang, Mengyin; Kang, Ting; Miao, Deyu; Tu, Yifan; Pang, Zhiqing; Song, Qing; Yao, Lei; Xia, Huimin; Chen, Hongzhan; Jiang, Xinguo; Gao, Xiaoling; Chen, Jun

doi:10.1016/j.biomaterials.2012.10.048

Cited by 177 publications

(103 citation statements)

References 49 publications

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“…Various molecular markers, selectively expressed on tumor cell surfaces, that distinguish tumor cells from normal cells provide the basis for the design of targeted, molecular-based cancer therapies. To date, various approaches based on ligand-targeted therapeutics (ie, antibodies, tumor-homing peptides or small molecular ligands) that can specifically bind to tumor-associated markers (ie, receptors) have been utilized to selectively kill tumor cells [4][5][6] . As an active targeting tool, antibodies bound to the cell surface antigens can promote the induction of antitumor immune responses by manipulating tumor-related signaling [7] or concentrate conjugated drug molecules to tumor cells expressing specific antigens [8,9] .…”

Section: Introductionmentioning

confidence: 99%

Molecular tumor targeting of gelonin by fusion with F3 peptide

2017

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Therapeutically potent macromolecular drugs have shown great promise for overcoming the limitations of small-molecule anti-cancer drugs. But tumor cell-selective intracellular delivery of the macromolecules remains a major hurdle for their successful clinical application. To overcome this challenge, we engineered a novel genetic fusion protein (F3-Gel) that composed of F3 peptide, a tumorhoming peptide, and gelonin, a plant-derived ribosome-inactivating protein (RIP), and then evaluated its anti-cancer activity in vitro and in vivo. The F3-Gel-encoding gene was synthesized by genetic recombination, and F3-Gel was successfully expressed in E coli. The anti-cancer activity of the produced F3-Gel was evaluated by various in vitro assays, which revealed that F3-Gel maintained equipotent protein synthesis inhibition activity (IC 50 =11 pmol/L) as unmodified gelonin (IC 50 =10 pmol/L). Furthermore, F3-Gel displayed enhanced cellular uptake into cancer cells (U87 MG, HeLa, LnCaP and 9L) than noncancerous cells (293 HEK and SVGp12). Compared with gelonin, F3-Gel exerted significantly higher cytotoxicity against these cancer cells. F3-Gel displayed significantly greater inhibition of protein translation in U87 MG cells: F3-Gel (0.5 μmol/L) was able to reduce the protein level to less than 50%, while gelonin (1 μmol/L) did not affect the intracellular protein level. In a U87 MG xenograft tumor-bearing mouse model, F3-Gel was accumulated in the tumor site at much higher levels and maintained for a prolonged time compared with gelonin. Administration of F3-Gel (0.5, 0.75 mol/kg, iv) caused 36% and 66%, respectively, inhibition of tumor growth in U87 MG xenograft mice, suggesting that it is a promising candidate drug for cancer treatment. Furthermore, this study demonstrates that fusion of F3 peptide to a potent macromolecule could provides an effective method for targeting tumors and eventually could improve their druggability.

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Section: Introductionmentioning

confidence: 99%

Molecular tumor targeting of gelonin by fusion with F3 peptide

2017

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“…Another tripeptide Asn-Gly-Arg (NGR) has been conjugated to different nanomedicines to target aminopeptidase N (CD 13) [75]. Moreover, the ability of the F3 peptide and the AS1411 aptamer to bind to nucleolin has been exploited to actively target nanomedicines to the brain tumor tissue [76,77].…”

Section: Systemic Delivery Of Nanomedicinesmentioning

confidence: 99%

Managing CNS Tumors: The Nanomedicine Approach

Aparicio-Blanco¹,

Torres-Suárez²

2017

New Approaches to the Management of Primary and Secondary CNS Tumors

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Albeit the rapidly evolving knowledge about tumor biochemistry enables various new drug molecules to be designed as treatments, malignant central nervous system (CNS) tumors remain untreatable due to the failure to expose the entire tumor to such therapeutics at pharmacologically meaningful quantities. Therefore, drug delivery in CNS tumors must be properly addressed, as otherwise, novel therapies will continue to fail. In this regard, nanomedicine poses an appealing platform for efficient drug delivery to the CNS, since it may be targeted to improve the drug availability in the site of action, which would be translated into lower drug doses and fewer side effects. Hence, the accumulation of data about the CNS physiology and their relevant receptors, the widening therapeutic armamentarium of drugs potentially useful in CNS chemotherapy and the alternative routes for administration may envisage nanomedicines as a forthcoming routine approach. Indeed, on the basis of the promising results gathered from preclinical studies of nanomedicine-based therapy both systemically and locally administered, some nanomedicines have already been approved for clinical trials in a variety of CNS tumor conditions to serve as the first steps in the translation of nanotherapy to clinic. Their outcome will steer research directions for further improvements.

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“…expressed, were used as the models of tumor cells and tumor neovascular endothelial cells, respectively. 20,22,23,47,48 Low cytotoxicity of the carrier itself is a primary concern in the development of a drug delivery system. Figure 6A and B shows the viability of MDA-MB-231 cells and HUVECs incubated with HMSN, pHMSN, or tHMSN for 48 hours (as determined by CCK-8 assay).…”

Section: Evaluation Of Drug-loading and Drug-release Propertiesmentioning

confidence: 99%

“…tLyp-1 (sequence CGNKRTR), 20,21 a newly reported heptapeptide which are screened by phage display library, is a ligand which is selectively targeted both to NRP1 and NRP2. Therefore, tLyp-1-decorated nanoparticles may be expected to have dual-targeting functions, and previous studies 22,23 have shown that such polymer nanoparticles have precise dual-targeting efficacy and penetrate extensively into tumor parenchyma.…”

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confidence: 99%

Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells

Liu¹,

Chen²,

Xu³

et al. 2015

IJN

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Background The purpose of this study was to construct hollow mesoporous silica nanoparticles (HMSN) decorated with tLyp-1 peptide (tHMSN) for dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells. Methods HMSN were synthesized de novo using a novel cationic surfactant-assisted selective etching strategy and were then modified with tLyp-1. Multiple methods, including transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, bicinchoninic acid assay, and nitrogen adsorption and desorption isotherms, were used to characterize the tHMSN. Doxorubicin were chosen as the model cargo, and the uptake of doxorubicin-loaded tHMSN into MDA-MB-231 cells and human umbilical vein endothelial cells (HUVECs), as models of tumor cells and tumor neovascular endothelial cells, respectively, were observed and detected by confocal laser scanning microscopy and flow cytometry. An in vitro pharmacodynamic study and a study of the mechanism via which the nanoparticles were endocytosed were also performed. Results HMSN with a highly uniform size and well oriented mesopores were synthesized. After tHMSN were characterized, enhanced uptake of the cargo carried by tHMSN into MDA-MB-231 cells and HUVECs compared with that of their unmodified counterparts was validated by confocal laser scanning microscopy and flow cytometry at the qualitative and quantitative levels, respectively. Further, the pharmacodynamic study suggested that, compared with their unmodified counterparts, doxorubicin-loaded tHMSN had an enhanced inhibitory effect on MDA-MB-231 cells and HUVECs in vitro. Finally, a preliminary study on the mechanism by which the nanoparticles were endocytosed indicated that the clathrin-mediated endocytosis pathway has a primary role in the transport of tHMSN into the cytoplasm. Conclusion tHMSN might serve as an effective active targeting nanocarrier strategy for anti-mammary cancer drug delivery.

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F3 peptide-functionalized PEG-PLA nanoparticles co-administrated with tLyp-1 peptide for anti-glioma drug delivery

Cited by 177 publications

References 49 publications

Molecular tumor targeting of gelonin by fusion with F3 peptide

Molecular tumor targeting of gelonin by fusion with F3 peptide

Managing CNS Tumors: The Nanomedicine Approach

Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells

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F3 peptide-functionalized PEG-PLA nanoparticles co-administrated with tLyp-1 peptide for anti-glioma drug delivery

Cited by 177 publications

References 49 publications

Molecular tumor targeting of gelonin by fusion with F3 peptide

Molecular tumor targeting of gelonin by fusion with F3 peptide

Managing CNS Tumors: The Nanomedicine Approach

Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and&nbsp;angiogenic blood vessel cells

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Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells