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Demethoxycurcumin-Carrying Chitosan–Antibody Core–Shell Nanoparticles with Multitherapeutic Efficacy toward Malignant A549 Lung Tumor: From in Vitro Characterization to in Vivo Evaluation
journal contribution
posted on 2015-04-06, 00:00 authored by Wei-Ting Huang, Mikael Larsson, Yen-Jen Wang, Shih-Hwa Chiou, Hui-Yi Lin, Dean-Mo LiuTargeting
controlled release core–shell nanocarriers with the potential
to overcome multidrug resistant (MDR) lung cancer were prepared based
on demethoxycurcumin (DMC) loaded amphiphilic chitosan nanoparticles
coated with an anti-EGFR antibody layer. The nanocarriers were characterized
with regard to size with dynamic light scattering, SEM, and TEM. The
characterization confirmed the nanocarriers to have a surface coating
of the anti-EGFR antibody and a final size excellently suited for
circulating targeting nanocarriers, i.e., <200 nm in diameter.
In vitro drug release revealed extended quasi-Fickian release from
the nanocarriers, with the anti-EGFR layer further reducing the release
rate. Cell culture experiments using normoxic and MDR hypoxic cells
overexpressing EGFR confirmed improved DMC delivery for anti-EGFR
coated particles and revealed that the DMC was delivered to the cytoplasmic
region of the cells, forming nanoprecipitates in lysosomes and endosomes.
The effective endocytosis and targeting of the core–shell nanoparticles
resulted in the nanocarriers achieving high cytotoxicity also against
MDR cells. The therapeutic potential was further confirmed in an A549
xenograft lung tumor mouse model, where DMC loaded core–shell
nanocarriers achieved about 8-fold reduction in tumor volume compared
with control group over the 8 weeks of the investigation. Both in
vitro and in vivo data suggest the anti-EGFR coated core–shell
nanocarriers as highly promising for treatment of hypoxic MDR cancers,
especially for non-small cell lung cancer.
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MDR cellssurface coatingVivo EvaluationTargetingMDR hypoxic cells overexpressing EGFRtumor volumehypoxic MDR cancersMultitherapeutic Efficacy549 xenograft lung tumor mouse modelcontrol groupcorecell culture experimentsrelease rateDMC deliverynanocarrierTEMamphiphilic chitosan nanoparticlesSEM8 weeksvivo datacytoplasmic regiondrug release549 Lung TumorVitro Characterizationlung cancer
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