A multiwalled carbon nanotube (MWNT)-based drug delivery system was developed by covalently combining carbon nanotubes with the antitumor agent 10-hydroxycamptothecin (HCPT) using hydrophilic diaminotriethylene glycol as the spacer between nanotube and drug moieties. The surface functionalizations of the nanotube were carried out by enrichment of carboxylic groups with optimized oxidization treatment, followed by covalently linking hydrophilic diaminotriethylene glycol via amidation reaction, and then HCPT was chemically attached to carbon nanotubes through a cleavable ester linkage. It is demonstrated that the obtained MWNT-HCPT conjugates are superior in antitumor activity both in vitro and in vivo to clinical HCPT formulation. In vivo single photon emission computed tomography (SPECT) imaging and ex vivo gamma scintillation counting analyses reveal that MWNT-HCPT conjugates have relatively long blood circulation and high drug accumulation in the tumor site. These properties together with the enhanced cell uptake and multivalent presentation of HCPT on a single nanotube benefit substantially the antitumor effects and would boost significantly the applications of carbon nanotubes in the biomedicine field.
Chitosan-gold hybrid nanospheres with varying surface zeta potentials were designed as a model system to investigate cell internalization. Gold nanoparticle was selected as optical marker to facilitate the visualization of the hybrid polymeric nanosphere internalization course and the localization in the cell by dark-field optical microscopy and transmission electron microscopy. It is found that surface potential has significant biological implications in the transmembrane efficiency, intracellular fate, and cytotoxicity of the hybrid nanospheres. Compared to those with lower surface potential, the spheres with higher surface potential show a faster cell uptake and enhance the nucleus targeting. However, too high a surface potential may destabilize the cell membrane and induce cell damage as well as cytotoxicity. These finding can help us to design suitable drug or gene nanocarriers with low cytotoxicity and high delivering ability.
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