Ligand-targeted particulate nanomedicines undergoing clinical evaluation: Current status

Meel, Roy van der; Vehmeijer, Laurens J. C.; Kok, Robbert J.; Storm, Gert; Gaal, Ethlinn V.B. van

doi:10.1016/j.addr.2013.08.012

Cited by 346 publications

(161 citation statements)

References 106 publications

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“…The in vivo results demonstrated that the expression level of VEGF165 protein in the CDG2-cRGD-5 group was significantly elevated compared with that in the CDG2 group (P,0.01) (Figure 8). This is consistent with previous studies 17,20 that on arrival at the target site, the ligand-conjugated delivery systems provide benefits in terms of cellular internalization.…”

Section: Discussionsupporting

confidence: 93%

“…19 Nevertheless, the ligand-conjugated delivery systems provide benefits in terms of cell internalization on arriving at their target cells. 20 Because systemic delivery remains one of the biggest challenges in clinical gene therapy, local gene delivery has been an attractive consideration when the target sites are locally confined or readily accessible, such as eyes, lung, and other organs. Local administration can avoid or delay RES uptake, reduce systemic toxicity, provide organ specificity, and help the delivery system reach the target cells.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial cell-targeted pVEGF165 polyplex plays a pivotal role in inhibiting intimal thickening after vascular injury

Tian¹,

Cao²,

Zou³

et al. 2015

IJN

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Upregulation of vascular endothelial growth factor (VEGF) expression can inhibit intimal thickening after vascular injury. However, the lack of efficient gene delivery systems leads to insufficient VEGF expression, which prevents its application in gene therapy. In the present study, to improve the delivery of the plasmid vector with the VEGF gene (pVEGF165) to the injured vessel wall, we explored the potentially important difference between endothelial cell-targeted and nontargeted polymeric carriers. The α v β 3 integrin is overexpressed on activated endothelial cells but not on normal quiescent vessels. In this study, CDG2-cRGD, synthesized by conjugating an α v β 3 integrin-binding cyclic arginylglycylaspartic acid (cRGD) peptide with the Generation 2 polycation polyamidoamine (PAMAMG2)-g-cyclodextrin (termed as CDG2), was developed as a targetable carrier. It was observed that the specific integrin–ligand interactions greatly enhanced cellular internalization of CDG2-cRGD in human umbilical vein endothelial cells (HUVECs), which are notoriously difficult to transfect. Consequently, HUVECs were found to show remarkably high levels of VEGF165 expression induced by the CDG2-cRGD polyplex. Interestingly, VEGF165 overexpression in vivo was more complex than that in vitro, and in vivo assays demonstrated that the stimulus response to balloon injury in arteries could obviously upregulate VEGF165 expression in the saline-treated group, although it was not enough to prevent intimal thickening. In gene-transfected groups, intravascular delivery of pVEGF165 with the CDG2-cRGD polyplex into rabbits after vascular injury resulted in a significant inhibition of intimal thickening at 4 weeks, whereas the low therapeutic efficacy in the nontargeted CDG2-treated group was only comparable to that in the saline-treated group. It is becoming clear that the conflicting results of VEGF165 gene therapy in two gene-transfected groups are reflective of the pivotal role of the cRGD-conjugated carriers in achieving the beneficial therapeutic effects of vascular gene therapy.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Endothelial cell-targeted pVEGF165 polyplex plays a pivotal role in inhibiting intimal thickening after vascular injury

Tian¹,

Cao²,

Zou³

et al. 2015

IJN

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“…With respect to immunoliposomes, although many preclinical studies can be found in the literature [24,215,275,276] and a few clinical trials are in progress [18,75,[277][278][279] an siRNA that targets PKN3 [18,286], or TKM-PLK1 that includes siRNA against PLK1 for the treatment of neuroendocrine tumors and adrenocortical carcinomas (phase I/II clinical trials) [283,287,288]. The phase I liposomic formulation SGT-53 includes plasmidic DNA that expresses the tumor suppressor gene p53 to treat solid tumors [280,289].…”

Section: Nl Cpt-11mentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,460

754

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Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

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“…252,253 However, this receptormediated endocytosis is a saturated pathway due to the limited number of receptors and the recycling of receptors during endocytosis. [254][255][256][257] On the other hand, most receptors such as ASGPR and FR are not only expressed on hepatoma cells but also on some normal cells, resulting in unfavorable uptake in these non-targeted cells.…”

Section: Dual-ligand Modification To Further Enhance Active Targetingmentioning

confidence: 99%

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

Li¹,

Zhang²,

Wang³

et al. 2016

IJN

117

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Ligand-targeted particulate nanomedicines undergoing clinical evaluation: Current status

Cited by 346 publications

References 106 publications

Endothelial cell-targeted pVEGF165 polyplex plays a pivotal role in inhibiting intimal thickening after vascular injury

Endothelial cell-targeted pVEGF165 polyplex plays a pivotal role in inhibiting intimal thickening after vascular injury

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

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