Functionalized O-carboxymethyl-chitosan/polyethylenimine based novel dual pH-responsive nanocarriers for controlled co-delivery of DOX and genes
作者： Mingfang Wang , Tingxian Liu , Leiqiang Han , Wenwen Gao , Shaomei Yang
DOI: 10.1039/C5PY00013K
关键词:
摘要: A novel dual pH-sensitive co-delivery system, programmed to respond tumor extracellular pH (6.0–7.0) and intracellular (4.5–6.5) environments, was designed for the controlled of DOX genes. Tumor cationic doxorubicin (DOX)–poly(ethyleneimine) (PEI) conjugates (DOX–PEI, DP) were synthesized via hydrazone bonds. As O-carboxymethyl-chitosan (CMCS) possesses charges under 6.5 is anionically charged above 7.0, triggered charge reversal CMCS–poly(ethylene glycol) (PEG)–aspargine–glycine–arginine (NGR) copolymers (CMCS–PEG–NGR, CPN) synthesized. The two materials with different properties help construct system. First, DP interacts anionic pDNA form a gene co-loaded DP/pDNA (DPD) core. Then, CPN adsorbed on surfaces positive DPD CPN/DPD (CDPD). CDPD exhibited spherical shapes, uniform particle size distributions (137.4 ± 2.7 nm 80.0 4.2 nm, respectively), zeta potentials (8.25 mV 23.59 mV, respectively). Targeted cellular uptakes confirmed (cellular 92.49 2.28% 67.82 0.07% in CD13-positive A549 cells CD13-negative HepG2 cells, dissociation from at acidic tissue evaluated (transfection efficiencies 7.4 6.0 11.43 0.59% 20.20 1.21%, internalized programmable release investigated simulated endosomal conditions. results suggest that conducive targeted delivery functional ensured successful construction using simple method.
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