Mass Transport via Cellular Barriers and Endocytosis - Intracellular Delivery: Fundamentals and Applications - page 38

Fig. 5 Schematic of mitochondrial translocases (Reprinted from Mokranjac and Neupert ( 2005 ).
Courtesy of Portland Press Limited Publishing Innovation)
lipophilic cell membrane (3) multidrug resistance (4) lysosomal accumulation and
inactivation of nanoparticles and (5) cationic polymer- or lipid-associated plasmid
DNA accumulation around the nucleus in the absence of targeting moieties (Holt
et al. 1988 ); targeting the mitochondria is possible through both “passive” and
“active” strategies. While some scientists suggest that only lower molecular weight
(<5kDa)BODIPY(boron-dipyrromethene)FL-labeledTPP(triphenylphosphonium)-
semitelechelic HPMA (hexamethylphosphoramide) copolymers exhibit significant
organelle localization or uptake (Callahan and Kopecek 2006 ), folate-modified
multifunctional nanoassemblies, approximately 200 nm in size loaded with both
docetaxel and iSur-pDNA (suppressor of metastatic and resistance-related protein
survivin) for hepatocellular carcinoma therapy, showed mitochondrial accumula-
tion (Biasutto et al. 2010 ; Xu et al. 2010 ). A proposed mechanism for mitochon-
drial targeting takes advantage of the negative membrane potential that builds up in
the mitochondria (130-150 mV) (Xu et al. 2010 ). Lipophilic cations such as tetra-
guanidinium oligomers or rhodamine-123 accumulate selectively within mitochon-
dria due to their membrane potential. “DQAsomes” (mitochondria-specific
nanocarrier system prepared from the amphiphilic quinolinium derivative dequal-
inium chloride) loaded with mitochondrial leader sequence-DNA conjugates and
paclitaxel have accumulated in mitochondria and resulted in reduced growth of a
human colon tumor mass in nude mice (Weissig 2003 ; Weissig et al. 2004, 2006 ).
Alternatively, conventional liposomes can be rendered mitochondria-specific via
the attachment of known mitochondriotropic residues to the liposomal surface
(Boddapati et al. 2005, 2008 ). MITO-Porter, a liposome-based carrier with a high
density of fusogenic R8 (octaArg) peptides conjugated to its surface has facilitated