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SCIENCE CHINA Materials, Volume 59, Issue 4: 254-264(2016) https://doi.org/10.1007/s40843-016-5035-6

光热响应的Cu7S4@pNIPAm纳米载体应用于可控的药物/光热治疗

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  • ReceivedMar 13, 2016
  • AcceptedApr 8, 2016
  • PublishedApr 15, 2016

Abstract

Drug delivery systems (DDSs) have been getting more and more attention in the field of cancer therapy with the development of nanotechnology. But remote and noninvasive controlled drug release for improving treatment efficacy and reducing side effects faces great challenge. We report a kind of “smart” nanocomposites (NCs) that is sensitive to the surrounding temperature by grafting a layer of thermo-sensitive polymer, poly(N-isopropylacrylamide) (pNIPAm), on the surface of single Cu7S4 nanoparticle (NP) via atom-transfer radical polymerization (ATRP). These NCs demonstrate a photothermal conversion efficiency of 25.4% under 808-nm near infrared (NIR) light irradiation and a drug loading content of 19.4% (drug/total NCs, w/w) with a lower critical solution temperature (LCST) of ~38°C. At normal physiological temperature (37°C), only 10.8% of the loaded doxorubicin (DOX) was released at physiological pH value (pH 7.4) within 10 h. In the presence of 808-nm irradiation, due to the temperature increment as a result of photothermal effects, DOX was rapidly released.


Acknowledgment

This research was supported by the National Natural Science Foundation of China (21475007, 21275015 and 21505003), the Fundamental Research Funds for the Central Universities (YS1406, buctrc201507 and buctrc201608), the “Innovation and Promotion Project of Beijing University of Chemical Technology”, the “Public Hatching Platform for Recruited Talents of Beijing University of Chemical Technology, the High-Level Faculty Program of Beijing University of Chemical Technology (buctrc201325), and BUCT Fund for Disciplines Construction and Development (XK1526)”.


Interest statement

The authors have declared that they have no conflict of interest.


Contributions statement

Wang L proposed the research direction and guided the project. Li Y and Xu M designed and performed the synthesis of the nanocarriers. Bai X performed the in vitro experiments. Hu G, Xu S and Wang L analyzed and discussed the experimental results, and drafted the manuscript. All the authors checked the manuscript.


Author information

Yuanbao Li is currently a third-year Master candidate in chemistry under the supervision of Prof. Leyu Wang at Beijing University of Chemical Technology (BUCT) since 2013. His research interest is focused on drug delivery and photothermal therapy with multifunctional nanocarriers.


Leyu Wang is a professor of chemistry at BUCT. He received his PhD in chemistry from Tsinghua University with Prof. Yadong Li in 2007. Then he joined Prof. Huang’s group at the University of California at Los Angeles (UCLA) as a postdoctoral researcher from 2007 to 2009. He moved to BUCT’s Department of Chemistry in October 2009. His research interests span from the controlled synthesis of upconversion luminescence nanoparticles (UCNPs), localized surface plasmon resonance (LSPR) near-infrared (NIR) semiconductor nanoparticles, magnetic nanomaterials, metal-semiconductor heteronanostructures, and molecularly imprinted polymers (MIPs) nanomaterials to the applications including electrocatalysis, artificial photosynthesis, biochemical sensing, multimodal imaging, drug/gene delivery and photothermo/chemo therapy.


Supplement

Supporting data are available in the online version of the paper.


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  • Scheme 1

    Scheme for the synthesis of photothermo sensitive nanocomposites and NIR light triggered release of DOX.

  • Figure 1

    TEM images (a, b) and DLS size distribution (c, d) of Cu7S4 NPs (a, c) and the NCs (b, d), respectively. (e) DLS size evolution plot of the NCs versus different temperatures. (f) DLS size analysis of the NCs by switching the temperature between 37 and 41°C.

  • Figure 2

    The temperature elevation profiles of the NCs suspension with continuous irradiation under 808-nm light: (a) 0.4 mg mL-1 of NCs suspension at different power densities; (b) different concentrations of NCs suspension at the same power density (1.0 W cm-2). The corresponding photothermal images after irradiation for 6 min were placed at the right side. (c) The temperature change profile of the NCs suspension under NIR irradiation (808 nm, 0.5 W cm-2) for 6 min and then the light source was shut off. (d) The linear fitting of the time from the cooling period of (c) vs. negative natural logarithm of driving force temperature.

  • Figure 3

    (a) DOX release profile of the NCs-DOX in PBS buffer (pH 7.4) at different temperatures; (b) DOX release profile of the NCs-DOX in PBS buffer (pH 7.4) in the absence and presence of 808-nm light (10 min, 1.0 W cm-2).

  • Figure 4

    Cell viability tests of the NCs and NCs-DOX on HeLa cell lines with and without 808-nm irradiation (1.0 W cm-2, 5 min) for a period of 24 (a) and 48 h (b), respectively.

  • Figure 5

    Fluorescence imaging of HeLa cell lines incubated with DOX-loaded NCs that were irradiated with (a–c) and without (d–f) 808-nm (1.0 W cm-2) light for 10 min. (g and h) The line-scanning fluorescence spectra along the line in the circle of (b) and (e), respectively.

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