Tumor-targeting

Poly(malic acid) is of pharmaceutical interest because its chemical derivatives may harbor both tissue-specific homing molecules and therapeutic effectors to be used for tissue (tumor) targeting in chemotherapy [2]. Because of its efficient production by fermentation, its biodegradability and nontoxicity, it is also considered as raw material in the industrial production of detergents, glues, and plastic materials. 

M. (1987). Tumor targeting potential of liposomes encapsulating Ga-67 and antibody to Dalton s lymphoma associated antigen (anti-DLAA), Int. J. Rad. Oncol. Biol. Phys.. 13, 1713-1719. 

Carrier for targeting to cancer Hydrolyzable targeting carrier for cancer Lung targeting tumor targeting Lysosomotropic carrier for cytotoxics Lysosomotropic carrier for cytotoxics... 

Pasqualini, R., Koivunen, E., and Ruoslahti, E. (1997). Alpha V integrins as receptors for tumor targeting by circulating ligands. Nat. Biotechnol. 15, 542-546. 

Koivunen E, Arap W, Valtanen H et al. Tumor targeting with a selective gelati-nase inhibitor. Nature Biotechnol 1999 17 768-774. 

Bloch, S., Lesage, F., McIntosh, L., Gandjbakhche, A., Liang, K. and Achilefu, S. (2005). Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice. J. Biomed. Opt. 10, 054003. 

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. 

Various researchers have applied the receptor-targeted strategy in pharmacological models for tumor-targeted delivery of pDNA expressing tumor necrosis factor alpha (TNFa). For example, Tf- or Tf-PEG-shielded PEI polyplexes have been used... 

Tf-containing PEG-shielded polyplexes have also been applied for systemic tumor-targeted delivery of siRNA [106-108]. Systemic treatment of Neuro 2A tumorbearing mice using Tf-PEG-shielded crosslinked oligoethylenimines for delivery of siRNA against Ras-related nuclear protein (Ran) led to >80% reduced Ran protein expression, associated with tumor apoptosis and reduced tumor growth [108]. 

Ogris M, Wagner E (2002) Tumor-targeted gene transfer with DNA polyplexes. Somat Cell Mol Genet 27 85-95... 

Kircheis R, Schuller S, Brunner S, Ogris M, Heider KH, Zauner W, Wagner E (1999) Polycation-based DNA complexes for tumor-targeted gene delivery in vivo. J Gene Med 1 111-120... 

Bellocq NC, Pun SH, Jensen GS, Davis ME (2003) Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene delivery. Bioconjug Chem 14 1122-1132... 

Koppu S, Oh YJ, Edrada-Ebel R, Blatchford DR, Tetley L, Tate RJ, Dufes C (2010) Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA. J Control Release 143 215-221... 

Chiu SJ, Ueno NT, Lee RJ (2004) Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin) conjugated polyethylenimine. J Control Release 97 357-369... 

Figure 7.16 The creation of a tumor-targeting dendrimer conjugate can take advantage of the multivalent character of the dendrimer polymer. This figure illustrates the attachment of five different groups to an amine-dendrimer to produce a chemotherapeutic construct.

Sato, N., Kobayashi, H., Saga, T., Nakamoto, Y., Ishimori, T., Togashi, K., Fujibayashi, Y., Konishi, J., and Brechbiel, M.W. (2001) Tumor targeting and imaging of intraperitoneal tumors by use of anti-sense oligo-DNA complexed with dendrimers and/or avidin in mice. Clin. Cancer Res. 7, 3606-3612. 

Gardner, C.R., Wasserman, A.J., and Laskin, D.L., Liver macrophage-mediated cytotoxicity toward mastocytoma cells involves phagocytosis of tumor targets, Hepatology, 14, 318, 1991. 

This applies primarily to such drugs as cancer chemotherapeutics that covalently bind to nucleic acids or other potential tumor targets and therefore have the inherent capability... 

McDevitt MR, Chattopadhyay D, Kappel BJ, Jaggi JS, Schififinan SR, Antczak C, Njardarson JT, Brentjens R, Scheinberg DA (2007) Tumor targeting with antibody-functionalized, radiolabeled carbon nanotubes. J. Nucl. Med. 48 1180-1189. 

Sonvico F, Mornet S, Vasseur S, Dubernet C, Jaillard D, Degrouard J, Hoebeke J, Duguet E, Colombo P, Couvreur P (2005) Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators synthesis, physicochemical characterization, and in vitro experiments. Bioconjugate Chemistry 16 1181-1188. 

McDevitt et al. (2007) reported that multiple copies of tumor-specific monoclonal antibodies were covalently attached to the carbon nanotubes. These tumor-specific antibodies should allow the carbon nanotubes to specifically target tumor cells. This will undoubtedly be beneficial to a patient and will most likely cause reduced side effects. These specific tumor-targeting CNTs may also have reduced... 

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