Original Article
CuS as a gatekeeper of mesoporous upconversion nanoparticles-based drug controlled release system for tumor-targeted multimodal imaging and synergetic chemo-thermotherapy

https://doi.org/10.1016/j.nano.2017.03.008Get rights and content

Highlights

  • The mesoporous core-shell upconversion NPs were synthesized as a drug carrier.

  • Disulfide bond was synthesized in a simple way.

  • UCL/MR/PAT guided intra-treatment monitor and post-treatment assessment of tumor.

Abstract

In this work, a tumor-targeted multifunctional mesoporous upconversion nanoparticle-based drug controlled release system was developed for UCL/MRI/PAT guided synergetic chemo-thermotherapy. Herein, the core-shell mesoporous upconversion nanoparticles served as drug carrier exhibiting higher upconversion luminescence emission intensity, with CuS as a gatekeeper through a cleavable disulfide bond under the influence of glutathione. CuS could not only prevent drug from early release during the delivery but also improve the delivery system function with the ability of photothermal therapy and photoacoustic tomography. Hyaluronic acid grafted on the surface of mesoporous upconversion nanoparticles could interact with CD44 receptors over-expressed in tumor cells, facilitating the drug delivery system to accumulate in tumor tissues. The synergy between chemotherapy and photothermal therapy was studied in vitro and in vivo, showing powerful anti-tumor effect. In cooperation with the multi-mode imaging, the size, site and morphology of tumor were clearly observed throughout the disease's progression.

Graphical Abstract

In this work, the core-shell mUCNPs served as drug carrier exhibiting higher UCL emission intensity, with CuS as a gatekeeper through disulfide bond cleavable under the influence of GSH. CuS could not only prevent drug from early release during the delivery but also improve the delivery system function with the ability of photothermal therapy and photoacoustic tomography. HA grafted on the surface of mUCNPs could interact with CD44 receptors overexpressed in tumor cells, facilitating the drug delivery system to accumulate in tumor tissues with high targeting ability. In cooperation with the UCL/MR/PAT imaging, the size, site and morphology of tumor were clearly observed throughout the tumor disease. As a whole, the smart drug delivery system will exert potential theranostic effect in future tumor diagnosis and treatment.

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Section snippets

Preparation and characterization of mUCNPs@DOX/CuS/HA

Details of the experiments about preparation and characterization of mUCNPs@DOX/CuS/HA were described in Supplementary data.

Redox stimuli responsive release of DOX from mUCNPs@DOX/CuS/HA system

To investigate the redox stimuli responsive release, mUCNPs@DOX/CuS/HA samples containing 1 mg DOX in dialysis bags (MWCO of 8, 000) were dialyzed in 50 mL PBS under different conditions, shaking at 140 rpm (37 °C). At specified time intervals, 1 mL samples of the release solution were taken out and replaced with an equal volume of fresh fluid. The release of DOX from the

Synthesis and characterization of nanoparticles.

The synthetic process of the mUCNPs-based nanoparticles connecting with CuS and HA via disulfide bonds was summarized in Figure 1. The core-shell mUCNPs were prepared through two step thermo-decomposition reaction. Via an amidation reaction, CuS and HA were covalently grafted onto the surfaces of mUCNPs. The solubility of the mUCNPs@DOX/CuS/HA nanocomposites was better than mUCNPs@DOX/CuS, owing to HA improving its biocompatibility, as shown in Figure 2, A.

The size and zeta potential of

Discussion

In this paper, we synthesized and characterized the mUCNPs@DOX/CuS/HA nanocomposites. Owing to HA, the solubility of the mUCNPs@DOX/CuS/HA nanocomposites was significantly improved. The TEM images showed that CuS evenly distributed on the surface and HA attached on the surface of samples. Moreover, the mesoporous NaGdF4 grown on the surface of NaYF4:Yb3+, Er3+ could significantly enhance the UCL emission intensity. Because the NaGdF4 shell had similar lattice constant with the core, which could

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  • Cited by (0)

    Source of finding: This work was supported by the National Natural Science Foundation of China (grant number 81503038) and Innovation Team Project of Zhengzhou City (grant number 121PCXTD521).

    Conflict of interest: None.

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