Distribution to Specific Organs

One of the most difficult challenges of administering cytotoxic chemotherapeutics involves unwanted exposure to non-cancer cells and to tissue and organ compartments not involved with the disease. Nanoparticles carrying a chemotherapeutic can reduce the undesirable distribution of such compounds as they are restricted from some compartments of the body such as the brain.59 Oppositely, nanoparticles can be modified, e.g., conjugation to chelators, to acquire the capacity to transport across the blood-brain barrier or BBB.124 Alternately, nanoparticles coupled to certain protein ligands such as apolipoprotein E can be used to target and transport across the BBB.125 In both cases, these nanoparticle delivery approaches lead to the unique distributions of materials that must be cleared and/or metabolized. Therefore, one consequence of targeting cancers cells is that the fate of these materials, by accessing and localizing to sites where cancer cells reside, may be affected that could affect their overall safety as well as efficacy.

Targeting to some cancers may require overcoming additional hurdles beyond interaction with specific cancer cell or tumor components. Some tumors are located in difficult-to-reach sites such as the brain and testes. Accessing these sites from the systemic vasculature requires that nanoparticle materials must first avoid systemic clearance by the RES and have the capacity to move across either the blood-brain or blood-testes barrier. Whereas some types of nanoparticles can keep materials out of compartments of the body such as the brain,59 other types of nanoparticles may provide access to this difficult-to-reach compartment.126 In general, surface characteristics that can be altered through chemical modifications can be used to regulate the targeted delivery of nano-particles to specific sites within the body such as the brain (reviewed in Olivier14). It has even been reported that coating nanoparticles with polysorbate 80 can facilitate brain targeting by enhancing their interaction with brain microvasculature.127 Alternately, intranasal delivery of macromolecules has been suggested to move in a retrograde fashion into the brain following uptake at the olfactory epithelium.128 Polylactic acid-PEG nanoparticles have been shown to transport across the nasal mucosa129 and could, theoretically, also provide some access to the brain because both materials appear to transport via a transcytosis mechanism.

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