Targeted of tumors

We have previously developed an in vivo selection method in which peptides that home to specific vascular beds are selected after intravenous administration of a phage display random peptide library [5]. This strategy revealed a vascular address system that allows tissue-specific targeting of normal blood vessels [6-8] and angiogenesis-related targeting of tumor blood vessels [3, 6, 9-12]. While the biologi-... 

In addition to the passive targeting of tumors due to the EPR effect, active targeting of PEGylated liposomes has also been successful. A study by Huwyler and coworkers (1996), for example, showed that coupling a monoclonal antibody to the surface of PEGylated liposomes resulted in significant transfer of the liposomes across the blood-brain barrier, which is difficult to achieve otherwise. The attached... 

This observation opens a window of opportunity, enabling a partially selective targeting of tumor cells in preference to host cells. By designing agents which attack nucleic acids at particular times during the cell cycle, it is possible to devise molecules with improved specificity for tumor cells. 

Favorable results with a new antibody therapy against breast cancer, HER2ncu (Hcrccptin), heralded a new era of tic at me nt based on molecular targeting of tumor cells... 

A. Targeting of Tumor-specific Dysfunctions in Cells Cycle Control or Apoptosis by Adenovirus Mutants... 

Liu S, Bugge TH, Leppla SH. Targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin. J Biol Chem 2001 276(21) 17976-17984. 

Kellner, R., Lichteneels, R., Atkins, D., Bukur,J., Ackermann, a.. Beck, J., Brenner, W., Melchior, S., Seliger, B. (2002). Targeting of tumor-associated antigens in renal cell carcinoma using proteome-based analysis and their clinical significance. Proteomics 2, 1743-1751. 

Recent work has been published on the use of SERS reporters for in vivo analysis. In 2008, Shuming Nie published work on the in vivo targeting of tumors in live mice [65]. The SERRS particles consisted of 60 nm gold nanoparticles functionalized with a Raman reporter dye molecule and then stabilized with thiolated polyethylene glycols (PEGs). Targeted SERS nanoparticles were prepared by having a mixed monolayer of thiolated PEG and a heterofunctional thiolated PEG with a carboxylic... 

Graff, C.P. and Wittrup, K.D., 2003. Theoretical analysis of antibody targeting of tumor spheroids importance of dosage for penetration, and affinity for retention, Cancer Res., 93, pp. 1288-1296. 

Vaidyanathan G, Affleck D J, Bigner D D, et al. (2002). Improved xenograft targeting of tumor-specific anti-epidermal growth factor receptor variant 111 antibody labeled using N-succinimidyl 4-guanidinomethyl-3-iodobenzoate. Nucl. Med. Biol. 29 1-11. 

Targeting Strategies Active Targeting of Tumor Vasculature and Tumor Cells... 264... 

There are a variety of interesting studies that successfully used B12 derivatives for selective targeting of tumor cells. In vitro, tumor cells have been specifically killed by cytotoxic B12 derivatives, involving a TC- and CD320-dependent uptake mechanism. In preclinical in vivo studies, radiolabeled or fluorescent B12 derivatives have been shown to accumulate in tumors. Consequently, tumors could be imaged in patients with an "Tn-labeled B12 derivative. However, the high uptake of B12 derivatives in healthy tissue poses a challenge for the successful use of cytotoxic B12 derivatives for cancer therapy. 

Z. Poon, D. Chang, X. Zhao, and P.T. Hammond, Layer-by-layer nanoparticles with a pH-sheddable layer for in vivo targeting of tumor hypoxia, ACS Nano, 5 (6), 4284-92,2011. 

Fain, H.D., Barrows, L, and Gao, Z. (2004) Ultrasound-triggered drug targeting of tumors in vitro and in vivo. Ultrasonics, 42, 943-950. 

The use of nanocontainers, such as low-density lipoproteins (LDL) or liposomes is the important approach directed to selective delivery of therapeutics into tumors. One of the observed differences between tumor cells and their normal counterparts is the rate of metabolism of low-density lipoproteins (LDLs). The LDL vesicle comprises a phospholipids/cholesterol shell with a diameter of approximately 15-20 nm, filled with cholesteryl and glyceryl esters of long-chain alkyl carboxylic acids. This difference is based on the increased need that tumor cells possess for cholesterol to facilitate new membrane formation. The overexpression of the LDL receptors on the tumor cell membrane is responsible for its LDL accretion. This provides a basis for cellular differentiation and the targeting of tumor cells with boron if cholesteryl esters of the LDL core are replaced with a boron species that would simulate cholesterol in its physiochanical properties. This concept was proposed by Kahl in the early 1990s. The initial compounds synthesized were esters of carborane carboxylic acid with various fatty acid alcohols [80]. Later, some other derivatives of cholesterol were synthesized [81,82] and LDLs were proposed as tumor delivery agents for carborane-containing porphyrins [83]. 

Danhier, R, Vroman, B., Lecouturier, N., Crokart, N., Pourcelle, V., Rreichels, H., Jerome, C., Marchand-Brynaert, J., Reron, O., Preat, V.J. Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with PacUtaxel. J. Control Release 140, 166-173 (2009)... 

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