Tumor vasculature targeting

NGR-TNF MolMed TNF fused to CNGRCG, a tumor vasculature-targeting (CD13) peptide Advanced solid tumors... 

Schiffelers RM et al (2003) Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. J Control Release 91 115-122... 

Taniguchi, K., Harada, N., Ohizumi, 1., Tsut-sumi, Y, Nakagawa, S., Kaiho, S., and Mayu-mi, T. (2000) Recognition of human activated CD44 by tumor vasculature-targeted antibody Biochem Biophys Res Commun 269, 671-675. 

Normalization of tumor vasculature Targeting vascular endothelial growth factor (VEGF) receptors to prune the immature, abnormal blood vessels, so more efficient drug penetration is achieved 147... 

Abu Lila, A.S. Ishida, T. Kiwada, H. Recent advances in tumor vasculature targeting using liposomal drug delivery systems. Expert Opin. Drug Deliv. 2009, 6 (12), 1297-1309. 

G. C. Krijger, M. M. Fretz, U. D. Woroniecka, O. M. Steinebach, W. Jiskoot, G. Storm, G. A. Koning. Tumor cell and tumor vasculature targeted liposomes for neutron capture therapy. Radiochim. Acta, 2005, 93, 589-593. 

Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279 377-380... 

In cancer treatment, passive targeting of macromolecular carriers to tumors is a commonly used approach. This passive targeting is based on the enhanced permeability and retention (EPR) effect, which leads to an accumulation of the high molecular weight carrier in the tumor tissue. The EPR effect arises from the different physiology of tumor vasculature, where the vessel walls are highly porous and lack the tight junctions that are present in healthy tissue. As a result, macromolecular carriers extravasate and accumulate preferentially in tumor tissue relative to normal tissues [63, 64]. 

Shielded polyplexes with improved blood circulating properties are interesting tools for systemic cancer therapy (see Sect. 4.2). Nanoparticles can take advantage of the enhanced permeability and retention (EPR effect) [89] for passive tumor targeting. The EPR effect is based on the leakiness of tumor vasculature, due to neovascularization in growing tumors, combined with an inadequate lymphatic drainage. Nanoparticles with an elongated plasma circulation time can extravasate and passively accumulate at the tumor site. 

The neoangiogenic tumor vasculature overexpresses certain integrins and other surface markers, which can also be used for targeting of polyplexes. The RGD peptide motif has been successfully applied for integrin-targeted pDNA [125-128] and siRNA [129, 130] delivery. In many cases, the PEG motif-containing peptide was attached to the polycation via a PEG spacer. For RGD-PEG-PEI/pDNA polyplexes, an optimum grafting with RGD-PEG was required because transfection... 

Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41 189-207... 

Mauceri HJ, Hanna NN, Wayne JD, et al. Tumor necrosis factor alpha (TNF-alpha) gene therapy targeted by ionizing radiation selectively damages tumor vasculature. Cancer Res 1996 56 4311-4314. 

Zhong H, Bowen JP. Antiangiogenesis drug design multiple pathways targeting tumor vasculature. Curr Med Chem. 2006 13 849-862. 

Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature, Science 275 547-550 (1997). 

Backer, M. V., Gaynutdinov, T. I., Patel V., et al. (2005) Vascular endothelial growth factor selectively targets boronated dendrimers to tumor vasculature. Mol. Cancer. Ther. 4, 1423-1429. 

Metastasis, the spread of cancer cells from a primary tumor to remote sites in the body, is frequently the ultimate cause of death from solid tumors. Current options for treatment or prevention of metastasis are very limited. Since vascularization of tumors (angiogenesis) provides conduits required for the spread of the tumor cells to other sites (metastasis), targeting tumor vasculature not only offers a noncytotoxic approach to eradicating primary solid tumors, it should also aid in preventing their spread via metastasis. 

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