Hybrid Organic Nanotubes with Dual Functionalities Localized on Cylindrical Nanochannels Control the Release of Doxorubicin

Abstract

A method to control the release of the anti-cancer drug doxorubicin (Dox) from cylindrical nanocapsules, known as organic nanotubes (ONTs), is reported. Co-assembly of a tube-forming glycolipid and its hydrophobized analogue yield novel ONTs with both -COOH and hydrophobic benzyloxycarbonyl groups localized on cylindrical nanochannels. The hydrophobicity of the ONTs nanochannels is easily tunable by adjusting the mixing ratio of the two glycolipids in the co-assembly process. The resultant biologically stable ONTs are able to capture Dox with high efficiency into the cylindrical nanochannels via ion complexation between cationic Dox and anionic -COO(-) , and the release of Dox from hybrid ONTs is effectively controlled by tuning the electrostatic interaction and the hydrophobicity. This controlled release by tuning the hydrophobicity of the ONTs' nanochannels greatly reduces the cytotoxicity of Dox@ONTs for HeLa cells.

Effects of PEGylation on the physicochemical properties and in vivo distribution of organic nanotubes

“…synthesis of Peg-lipid 2 and DOTa-lipid 3 PEG-tethered lipid analogue (PEG-lipid) 2 was synthesized by the coupling of mono-PEGylated eicosanedioic acid (MW of PEG: 2000) 13 with glycyl-glycyl-glycyl-glycine methyl ester 15 using DMT-MM as a coupling agent ( Figure 2). After 4 hours' reaction at room temperature, methanol was removed and the residue was redispersed in water for dialysis (MWCO 3,500).…”

“…DOTA-lipid 3: 19-(N-β-d-glucopyranosyl carbamoyl) nonadecanoyl-glycyl-glycyl-glycyl-ethyl ester was synthesized in a similar process as previously reported. 15 It was aminolyzed with excess ethylenediamine in dimethyl sulfoxide (DMSO) at 80°C. Addition of methanol gave a precipitation of 19-(N-β-d-glucopyranosyl carbamoyl) nonadecanoyl-glycyl-glycyl-glycyl-ethylamine.…”

“…In contrast to those poorly dispersed ONTs, 21,22 we have successfully developed highly water-dispersed and biologically stable ONTs with an outer diameter less than 20 nm. 15,16,23 In our in vitro studies, these ONTs are effective as nanocarriers in terms of high loading for anticancer drugs and proteins and controlled release property, but in vivo validation is indispensable to advance the ONTs into potential drug nanocarriers. We expect that these ONTs having smaller size, higher dispersibility, and higher stability may improve their biodistribution and biological effect.…”

Aging-Related Peculiarities of the Distribution of Myelin Basic Protein in Cerebral Structures of Gerbils

“…The formation of myelin sheaths is based on spiral enlacing of neuronal axons by the processes of specialized glial cells, oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS) [3]. Myelin forms specific membrane structures built by a lipid bilayer and proteins linked with the latter [4,5]. A high lipid/protein ratio is one of the biochemical characteristics differentiating myelin from other protein/lipid complexes.…”

Synthesis and characterization of nanoarchitectures from fatty acid derivatives of 2,6-diaminopyridine and 2-aminopyridine

“…The organic nanotubes can provide suitable hollow cylindrical space for biomacromolecules that are at least 10 times larger in dimension as compared to macrocylic molecules used for host-guest study [16]. Because of the confined nanospace, lipid nanotubes (LNTS) have found potential in chemical and biological applications [17][18][19][20][21][22][23], including controlled drug release [19][20][21][22] and artificial chaperoning of denatured protein [23]. Lipid nanotube was used as template for the synthesis of titania, tantalum oxide and vanadium oxide nanotubes [24].…”