Tumor delivery

Cooke, S.P., R.B. Pedley, R. Boden, R.H. Begent, and K.A. Chester, In vivo tumor delivery of a recombinant single-chain Fvr.tumor necrosis factor a fusion protein. Bioconjug Chem, 2002.13(1) 7-15. 

Polymer platinate SiRNA Platinum tumor delivery Cytotoxic... 

Sung MW, Chen SH, Thung SN, Zhang DY, Huang TG, Mandeli JP, Woo SL. Intra-tumoral delivery of adenovirus-mediated interleukin-12 gene in mice with metastatic cancer in the liver. Hum Gene Ther 2002 6 731 43. 

There are basically two delivery routes for drugs intravenous delivery and intra-tumoral delivery [10, 15]. Intravenous delivery is being extensively used for the chemotherapeutic agent bleomycin, with good success. Indeed there are several aspects that make this a favorable soluhon. First, bleomycin does not readily enter cells. Therefore, an intravenous delivery will have a favorable toxicity profile despite whole-body exposure to the drug. Second, the increase in toxicity is very marked once direct access to the cell cytosol is provided thus even a limited local dose will exert a sufficient effect. Other drugs to be administered intravenously for delivery during electroporahon would need to be able to fulfill this criterion, in order to have both sufficient effects in the treated area as well as a favorable toxicity profile. 

High distribution of [methyl-"C]temozo-lomide, a DNA methylating agent, to tumors has also been demonstrated by PET. In patients with brain tumors, delivery and exposure of the radiotracer was found... 

A. Barel, G. Jori, A. Perin, P. Romandini, A. Pagnan, S. Biffanti (1986). Role of high-, low- and very low-density lipoproteins in the transport and tumor-delivery of hemato-porphyrin in vivo. Cancer Lett., 32, 145-150. 

Enhanced delivery to tumors is a similarly important appUcatiOTi of ultrasound-enhanced drug and gene delivery, since transport of drugs within solid tumors can be very limited. Rapoport and coworkers reported an increase in localised tumor delivery of up to 5-10 fold by using sonic activation (Rapoport et al. 2007 Husseini and Pitt 2008). 

Yin, H. Bae, Y. H. pH-Triggered Micelles for Tumor Delivery, in Drug Delivery in Oncology From Basic Research to Cancer Therapy, Wiley-VCH Weinheim, Germany, 2011. 

K. Sasagawa, T. Kobayashi and M. C. Hisaoka, Enhanced tumor delivery and antitumor activity of palmitoyl rhizoxin using stable lipid emulsions in mice. Pharm. Res., 13,305-310 (19%c). 

Li, C. J., Miyamoto, Y., Kojima, Y., and Maeda, H., 1993, Augmentation of tumor delivery of macromolecular drugs with reduced bone marrow delivery by elevating blood pressure. Br. J. Cancer 67 975-980. 

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]. 

Chapter 10 Boron Tumor Delivery for BNCT Recent Developments and Perspectives...209... 

Torchilin, V Tumor delivery of macromolecular drugs based on the EPR effect. Adv. Drug Deliv. Rev. 63, 131-135 (2011)... 

This eoncept was proposed by Kahl at the begiiming of 1990s. The initial compoimds synthesized were esters of earborane earboxylic aeid with various fatty acid alcohols [187], Later some other derivatives of eholesterol were synthesized [188-193], More recently LDLs were proposed as tumor delivery agents for earborane-eontaining porphyrins [194]. 

An important study by Lee et al. showed, for the first time, the in vivo use of the tetrahedron as a carrier of siRNA sequences for tumor delivery (Fig. 1.6(2) Lee et al., 2012). In this study each edge of the tetrahedron contained a protruding overhang DNA sequence to which an extended siRNA sequence could hybridize. The siRNAs sequences were further modified with folic acid (FA) in such a way that in the final nanostructure siRNA-FA molecules were placed at defined geometrical orientations. The structure was shown to have a hydrodynamic size of around 29 nm. After i.v. delivery in a xenograft tumor mouse model, the nanostructures were seen to specifically accumulate in the tumor and downregulate luciferase from implanted Luc-modified KB cancer cell line. 

Adams GP, Schier R, Marshall K, Wolf EJ, McCall AM, Marks JD, Weiner LM. Increased affinity leads to improved selective tumor delivery of single-chain Fv antibodies. Cancer Res 1998 58 485-490. 

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