期刊
ACS APPLIED MATERIALS & INTERFACES
卷 9, 期 16, 页码 13865-13874出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b01120
关键词
swollen micelles; squeezing effect; gating; pH-responsive nanoparticles; doxorubicin
资金
- China Scholarship Council [201506455008]
- National Natural Science Foundation of China [21176257]
- Australian Research Council (ARC)
Natural variations in pH levels of tissues in the body make it an attractive stimuli to trigger drug release from a delivery vehicle. A number of such carriers have been developed but achieving high drug loading combined with low leakage at physiological pH and tunable controlled release at the site of action is an ongoing challenge. Here we report a novel strategy for the synthesis of entirely hydrophilic stimuli-responsive nano carriers with high passive loading efficiency of doxorubicin (DOX), which show good stability at pH 7 and rapid tunable drug release at intracellular pH. The particles (D-h = 120-150 nm), are prepared by cross-linking: the core of swollen micelles of the triblock copolymer poly[poly(ethylene glycol) methyl ether methacrylate-b-N,N'-di(methylamino)ethyl methaerylate-b-tertbutyl methactylate](poly(PEGMEMA)-b-PDMAEMA-b-PtBMA)). After subsequent deptotectiori of the tert-butyl groups a hydrophilic poly(methacrylic acid) (PMAA) core is revealed: Due to the negative charge in the acidic core the particles absorb 100% of the DOX from solution at pH 7 at up to 50 wt % DOX/polymer, Making them extremely simple to load. Unlike other systems, the DMAEMA gating shell ensures low drug leakage at pH 7, whereas physical shrinkage of the MA A. core allows rapid release below pH 6. The,particles deliver DOX with high efficiency to human pancreatic cancer AsPC-1 cell lines, even lowering the IC50 of DOX. As the particles are stable as a dry powder and can be loaded with any mixture of positively charged drugs without complex synthetic or purification steps, we propose they will find use in a range of delivery applications.
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