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A biodegradable brush-type copolymer PHF-g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.

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Gemcitabine [2 0 ,2 0 -difluoro-2 0 -deoxycytidine (dFdC)], firstline treatment for pancreatic cancer in the clinic, is a cytotoxic nucleoside analogue. Nucleoside transporters are required in the transport of gemcitabine into cells since it is a hydrophilic compound. Actually, there are significant drawbacks for the application of gemcitabine in clinic, including a short half-life and serious side effects. In order to overcome the mentioned drawbacks, a novel prodrug, cholesteryl hemisuccinate-gemcitabine (CHSdFdC), was synthesized through covalently coupling the amino group of gemcitabine with the carboxylic group of cholesteryl hemisuccinate. The amphiphilic prodrug self-assembled spontaneously as nanoparticles in aqueous media confirmed by transmission electron microscopy (TEM). Dynamic light scattering (DLS) measurement revealed that the mean particle size is approximately 200 nm in aqueous media. The CHSdFdC nanoparticles displayed accumulative controlled drug release in simulated lysosome conditions (pH 5.0 NaAc buffer solution containing cathepsin B); the amount of drug release reached up to 80% within 10 h. However, there was almost no drug release in pH 7.4 PBS and pH 5.0 NaAc buffer solutions without cathepsin B. All these results indicated the intracellularly controlled drug release manner of the CHSdFdC nanoparticles. The controlled release of dFdC from the CHSdFdC nanoparticles was related closely to cleavage of amide bonds by cathepsin B. The CHSdFdC nanoparticles exhibited increased ability to inhibit cell growth compared with gemcitabine in vitro. Meanwhile, the CHSdFdC nanoparticles exhibited enhanced cellular uptake ability against Bxpc-3 cells, and the amount of CHSdFdC was about 15 fold of gemcitabine during the 2.5 h incubation. All these results showed that the CHSdFdC nanoparticle prodrug has great potential in the treatment of pancreatic cancer.

To enhance biocompatibility and physiological stability of hydrophobic MnO nanoparticles as contrast agent of T 1weighted magnetic resonance imaging (MRI), dopamine-functionalized poly(ethylene glycol) (PEG) was used to coat the surface of about 5 nm MnO nanoparticles. Although hydrophilic coating might decrease longitudinal relaxivity due to inhibiting the intimate contact between manganese of nanoparticle surface and proton in water molecules, higher longitudinal relaxivity was still maintained by manipulating the PEGylation degree of MnO nanoparticles. Moreover, in vivo MRI demonstrated considerable signal enhancement in liver and kidney using PEGylated MnO nanoparticles. Interestedly, the PEGylation induced the formation of about 120 nm clusters with high stability in storing and physiological conditions, indicating passive targeting potential to tumor and prolonged circulation in blood. In addition, the cytotoxicity of PEGylated MnO nanoparticles also proved negligible. Consequently, the convenient PEGylation strategy toward MnO nanoparticles could not only realize a good "trade-off" between hydrophilic modification and high longitudinal relaxivity but also contribute additional advantages, such as passive targeting to tumor and long blood circulation, to MRI diagnosis of tumor.