Tumor tissues targeting

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]. 

Tumor tissues overexpress matrix metalloproteinases (MMPs). A liposomal pDNA carrier (MEND) was developed containing PEG conjugated to lipid via a peptide linker that is a target sequence for MMPs. In this strategy, PEG is removed from the carrier via MMP-triggered cleavage [198]. Intravenous administration in... 

Pun SH, Tack F, Bellocq NC, Cheng J, Grubbs BH, Jensen GS, Davis ME, Brewster M, Janicot M, Janssens B, Floren W, Bakker A (2004) Targeted delivery of RNA-cleaving DNA enzyme (DNAzyme) to tumor tissue by transferrin-modified, cyclodextrin-based particles. Cancer Biol Ther 3 641-650... 

Fig. 2.2-1. A neutron capture event seen in relation to the size of the target. Electron microscopic image of uncontrasted tumor tissue, stained for boron by antibodies. The smaller structure surrounded by clusters of dots is the nucleus. The thin structure lined with dots is the cell membrane. The dots are gold particles attached to the antibodies which are specifically directed against the...

When specific compounds for BNCT are to be prepared, the cluster compounds must be covalently attached to organic moieties. The chemistry of such reactions will be the focus of this chapter. It should be borne in mind, however, that the boron spedes might in themselves already constitute suitable candidates for selective accumulation or retention in tumors, and perhaps also possess other pharmacological properties. Thus, Na2Bi2HnSH (BSH) (see Section 2.2.5.1), which is clinically used for BNCT of glioblastoma [2], and its thiocyanate derivative Na2Bi2HnSCN [12], are both taken up in tumor tissue without additional targeting units. 

The pharmacokinetics of a gene drug within tumor tissue is a very important issue because cancer becomes one of the major targets for gene therapy, and various protocols are now under clinical trials (Roth and Cristiano, 1997). For in vivo gene delivery protocols, a gene drug, free or complexed with vector, is sometimes... 

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