Objective:Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery of anticancer drugs to the lungs.
Methods:hTe following nanocarriers were studied:micelles, liposomes, mesoporous silica nanoparticles (MSNs), poly propyleneimine (PPI) dendrimer-siRNA complexes nanoparticles, quantum dots (QDs), and poly (ethylene glycol) polymers. All particles were characterized using the following methods:dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto-and genotoxicity. In vivo organ distribution of all nanoparticles, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice atfer the pulmonary or intravenous delivery.
Results:Signiifcant differences in lung uptake were found atfer the inhalation delivery of lipid-based and non-lipid-based nanoparticles. hTe accumulation of liposomes and micelles in lungs remained relatively high even 24 h atfer inhalation when compared with MSNs, QDs, and PPI dendrimers. hTere were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h atfer inhalation or intravenous administrations, but 24 h atfer intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes signiifcantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer.
Conclusion:hTe results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers atfer the inhalation delivery. hTese particles are most suitable for effective inhalation treatment of lung cancer.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Most of the patients with HCC lose the surgical opportunity at the time of diagno-sis. Some novel therapeutic modalities, like gene therapy, are promising for the treatment of HCC. However, the success of gene therapy depends on two aspects: efficient gene materials and gene delivery vectors. The present study was to develop new chitosan-based nanoparticles for a midkine-siRNA (anti-HCC gene drug) delivery.
METHODS: The novel gene delivery vector (MixNCH) was syn-thesized by hybrid-type modification of chitosan with 2-chloro-ethylaminehydrochlorideandN,N-dimethyl-2-chloroethylamine hydrochloride. The chemical structure of MixNCH was char-acterized by FT-IR and 1HNMR. The cytotoxicity of MixNCH was determined by MTS assay. The gene condensation ability and size, zeta potential and morphology of MixNCH/MK-siRNA nanoparticles were measured. The in vitro transfection and gene knockdown efficiency of midkine by MixNCH/MK-siRNA nanoparticles was detected by qRT-PCR and Western blotting. Gene knockdown effect at the molecule level on the proliferation of HepG2 in vitro was determined by MTS assay.
RESULTS: MixNCH was successfully acquired by aminoalkyl-ation modification of chitosan. The MixNCH could condense MK-siRNA well above the weight ratio of 3. The average size of MixNCH/MK-siRNA nanoparticles was 100-200 nm, and the surface charge was about +5 mV. Morphologically, MixNCH/MK-siRNA nanoparticles were in regular spherical shape with no aggregation. Regarding to the in vitro transfection of nanoparticles, the MixNCH/MK-siRNA nanoparticles reduced MK mRNA level to 14.03%±4.03%, which were comparable to Biotrans (8.94%±3.77%). MixNCH/MK-siRNA effectively inhibited the proliferation of HepG2 in vitro.
CONCLUSION: MixNCH/MK-siRNA nanoparticles could be effective for the treatment of hepatocellular carcinoma.