Abstract
In this article, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. The polymeric mPEG-Chitosan-Ketal (PCK) carrying pH-sensitive ketal group as hydrophobic moieties and PEG group as hydrophilic moieties were synthesized. The two pH-sensitive ketal derivatives were employed to fabricate nanoparticles for anti-tumor drug delivery. The oHM-PCK nanoparticles (oHPN) can spontaneously self-assemble into mixed micellar structure with nano-sized spherical shape of 100–200 nm at pH 7.4 PBS conditions. The oHPN could release encapsulated curcumin with 92.6 % at pH 5.0 compared with 55.3 % at pH 7.4. The results of cytotoxicity assay indicated that encapsulated curcumin in oHPN (Cur-oHPN) have less toxicity compared to curcumin suspension. The anti-tumor efficacy in vivo suggested that Cur-oHPN suppressed tumor growth most efficiently. These results present the promising potential of oHPN as an effective nano-sized pH-sensitive drug delivery system for intracellular delivery.
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Acknowledgments
This study is financially supported by the National Natural Science Foundation of China (no.81302718), Taishan Scholar Project (To Dr. Zimei Wu), Young Core Instructor Visitor Foundation of Shandong Province, China (2014), Young Core Instructor Training Program of Yantai University, China (2014).
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The authors report no conflicts of interest in this work.
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Daquan Chen and Zimei Wu have contributed to this work equally.
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Chen, D., Sun, J., Lian, S. et al. Dual pH-responsive and CD44 receptor targeted multifunctional nanoparticles for anticancer intracellular delivery. J Nanopart Res 16, 2743 (2014). https://doi.org/10.1007/s11051-014-2743-1
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DOI: https://doi.org/10.1007/s11051-014-2743-1