Assessing the therapeutic efficacy of VEGFR-1-targeted polymer drug conjugates in mouse tumor models

Golan, Moran; Tyomkin, Dalia; David, Ayelet

doi:10.1016/j.jconrel.2016.03.024

Cited by 22 publications

(10 citation statements)

References 34 publications

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“…Realizing the importance of selectins in cancer development and their potential for therapeutic targeting, several selectin-directed delivery systems were recently synthesized. Shamay and colleagues demonstrated an anti-tumor activity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugated to an E-selectin binding peptide and loaded with different anti-cancer agents ( Shamay et al, 2016b ; Shamay et al, 2015 ). Another P-selectin targeted drug delivery system was designed by encapsulating chemotherapies with fucoidan (Fi), an algae-derived polysaccharide with an affinity to P-selectin.…”

Section: Discussionmentioning

confidence: 99%

Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome

Ferber

Tiram

Sousa-Hervés

et al. 2017

eLife

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Glioblastoma is a highly aggressive brain tumor. Current standard-of-care results in a marginal therapeutic outcome, partly due to acquirement of resistance and insufficient blood-brain barrier (BBB) penetration of chemotherapeutics. To circumvent these limitations, we conjugated the chemotherapy paclitaxel (PTX) to a dendritic polyglycerol sulfate (dPGS) nanocarrier. dPGS is able to cross the BBB, bind to P/L-selectins and accumulate selectively in intracranial tumors. We show that dPGS has dual targeting properties, as we found that P-selectin is not only expressed on tumor endothelium but also on glioblastoma cells. We delivered dPGS-PTX in combination with a peptidomimetic of the anti-angiogenic protein thrombospondin-1 (TSP-1 PM). This combination resulted in a remarkable synergistic anticancer effect on intracranial human and murine glioblastoma via induction of Fas and Fas-L, with no side effects compared to free PTX or temozolomide. This study shows that our unique therapeutic approach offers a viable alternative for the treatment of glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome

Ferber

Tiram

Sousa-Hervés

et al. 2017

eLife

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“…Recently, we also demonstrated that 125 I-F56 11 and 64 Cu-DOTA-F56 12 could specifically target VEGFR1 for noninvasive molecular imaging of gastric tumors. Moreover, some groups designed F56-conjugated nanoparticles for neovasculature imaging 13 or utilized the specificity of F56 to enhance the therapeutic effect of cytotoxic drugs 14 , 15 . Thus, F56 offers potent benefits for cancer therapy and diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Development of a novel albumin-based and maleimidopropionic acid-conjugated peptide with prolonged half-life and increased in vivo anti-tumor efficacy

Feng¹,

Zhao²,

Wang³

et al. 2018

Theranostics

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Angiogenesis plays a critical role in tumor aggressiveness, and a lot of anti-angiogenic agents have been used in clinical therapy. The therapeutic efficacy of peptides are generally restricted by the short in vivo life-time, thus, we were interested in developing a novel albumin-based and maleimidopropionic acid-conjugated peptide to prolong the half-life and improve the anti-tumor effect.Methods: We developed a peptide F56 with a maleimidopropionic acid (MPA) at the C-terminal (denoted as F56-CM), which allows immediate and irreversible conjugation with serum albumin. Biological property and anti-tumor activity of F56-CM were evaluated in vitro and in vivo.Results: We showed that F56-CM reduced migration and tube formation of endothelial cells in vitro and inhibited the generation of subintestinal vessels (SIV) in zebrafish embryos in vivo. F56-CM inhibited vascular endothelial growth factor (VEGF) induced phosphorylation of VEGFR1 and activation of the PI3K-AKT axis. Furthermore, F56-CM rapidly conjugated with albumin upon intravenous injection and extended the biological half-life of F56 from 0.4249 h to 6.967 h in rats. Compared with F56, F56-CM exhibited stronger anti-tumor activity on both BGC-823 gastric cancer and HT-29 colon cancer xenografts in nude mice, and the statistical difference was remarkable. More significantly, the efficacy of F56-CM inhibiting lung metastasis of BGC-823 cells was also better than that of F56. The inhibition rates were 62.1% and 78.9% for F56 and F56-CM respectively when administrated every day, and 43.8% and 63.1% when administrated every four days at equal dose.Conclusions: Taken together, our results demonstrated that F56-CM has considerable potential for cancer therapy.

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“…Shamay et al prepared vascular endothelial growth factor receptor (VEGFR)-1-targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugate incorporated with doxorubicin. The binding and internalization profiles of HPMA-doxorubicin conjugate indicated that this conjugate is superior to endothelial cells when compared to cancer cells [136]. The cytotoxicity studies of the polymer-drug conjugate indicated an IC 50 value of 0.15 µM against bEnd.3 cells, which was 370-fold cytotoxic when compared to the peptide-doxorubicin.…”

Section: Polymer-anticancer Drug Conjugates For Lung Cancer Treatmentmentioning

confidence: 96%

Polymer-Drug Conjugate, a Potential Therapeutic to Combat Breast and Lung Cancer

2020

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Cancer is a chronic disease that is responsible for the high death rate, globally. The administration of anticancer drugs is one crucial approach that is employed for the treatment of cancer, although its therapeutic status is not presently satisfactory. The anticancer drugs are limited pharmacologically, resulting from the serious side effects, which could be life-threatening. Polymer drug conjugates, nano-based drug delivery systems can be utilized to protect normal body tissues from the adverse side effects of anticancer drugs and also to overcome drug resistance. They transport therapeutic agents to the target cell/tissue. This review article is based on the therapeutic outcomes of polymer-drug conjugates against breast and lung cancer.

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Assessing the therapeutic efficacy of VEGFR-1-targeted polymer drug conjugates in mouse tumor models

Cited by 22 publications

References 34 publications

Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome

Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome

Development of a novel albumin-based and maleimidopropionic acid-conjugated peptide with prolonged half-life and increased in vivo anti-tumor efficacy

Polymer-Drug Conjugate, a Potential Therapeutic to Combat Breast and Lung Cancer

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