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Folate-conjugated pH-controllable fluorescent nanomicelles acting as tumor targetable drug carriers

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Abstract

The authors describe biocompatible nanomicelle based drug carriers that can be used for simultaneous (a) fluorescence tracking, (b) pH-controlled release of the cancer drug doxorubicin (DOX), and (c) targeting the folate receptor. The pH-sensitive triblock copolymer is composed of poly-2-(diisopropylamino) ethyl methacrylate and methoxypoly (ethylene glycol) which were prepared by radical polymerization and ‘click’ chemistry. The copolymers undergo self-assembly to form spherical micelles with diameters between 100 and 200 nm and a pH-trigger capability at pH values from 5.8 to 6.2. The micelles enabled DOX to be released at pH 5.0 at a much higher rate than at pH 7.4. Studies on cellular uptake revealed selective internalization of the DOX-loaded nanomicelles into HeLa cells where they can be imaged fluorometrically. Quantitative analysis of the green fluorescence indicated that the FITC-labeled micelles possess a transfection efficiency of about 79% while that of the nanomicellles with folate is only ∼40% under the same conditions. Confocal laser scanning microscopy indicates that the micelles invade the lysosome of HeLa cells and that the DOX released by micelles causes strong cell lethality. In our preception, this work provides useful insights in terms of designing multifunctional drug carriers and of improving the applicability of copolymer micelles for drug delivery systems.

Schematic of the preparation of multi-functional nanomicelles through self-assembly of amphipathic polymers. The micelles act as tumor targeting and pH-controllable drug carriers. FITC/FA/P100-M can invade the lysosome of HeLa cells and release DOX inside cells, this leading to strongt cell lethality.

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Acknowledgements

Financial support for this work was provided by the National Natural Science Foundation of China (No. 21276074), National Natural Science Foundation of China for Innovative Research Groups (No. 51621002).

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Authors and Affiliations

  1. Key Laboratory for Advanced Materials and Department of Chemistry, East China University of Science and Technology, Shanghai, 200237, China

    Weiju Hao, Tong Wang, Danyang Liu, Yazhuo Shang, Shouhong Xu & Honglai Liu

  2. Key Laboratory of Medical Molecular Virology (Ministry of Health and Ministry of Education), School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, People’s Republic of China

    Junqi Zhang

Authors
  1. Weiju Hao
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  2. Tong Wang
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  3. Danyang Liu
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  4. Yazhuo Shang
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  5. Junqi Zhang
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  6. Shouhong Xu
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  7. Honglai Liu
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Correspondence to Junqi Zhang or Shouhong Xu.

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Weiju Hao and Tong Wang equally contributed to this work.

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Hao, W., Wang, T., Liu, D. et al. Folate-conjugated pH-controllable fluorescent nanomicelles acting as tumor targetable drug carriers. Microchim Acta 184, 2881–2891 (2017). https://doi.org/10.1007/s00604-017-2255-7

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  • DOI: https://doi.org/10.1007/s00604-017-2255-7

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