Original Article
Superior temperature sensing of small-sized upconversion nanocrystals for simultaneous bioimaging and enhanced synergetic therapy

https://doi.org/10.1016/j.nano.2019.102135Get rights and content

Abstract

The upconversion nanoparticles (UCNPs) exhibit versatility applications aiming at biological domains for decades on account of superior optical characteristics. Nevertheless, the UCNPs are confronted with tremendous difficulties in biological field owing to large grain size, low fluorescence efficiency, and single function. Herein, the small-sized CaF2: Yb3+/Er3+ UCNPs coated with NaGdF4 shells (activator and inert, UCNPs-RBHA-Pt-PEG) not only burst out strong fluorescence, but also provide prominent diagnosability by taking advantage of magnetic resonance (MR) imaging as well as temperature sensing and inhibiting capability for CT26 tumor tissues based on synergetic therapy modality of photodynamic therapy (PDT) and chemotherapy. Ultimately, the tumor sizes decrease visibly after injected with UCNPs-RBHA-Pt-PEG and simultaneously irradiated with near infrared (NIR) light at low power density (0.35 W/cm2, 6 min). In summary, the small-sized and strong-fluorescent single nanoparticles with multi-functions may provide a valuable enlightenment for diagnosis and treatment of cancer in the future.

Graphical abstract

The small-sized and enhanced-fluorescent CaF2 UCNPs emit strong fluorescence after coated with NaGdF4 shells (activator and inert). The ample PDT efficacy is achieved relied on the fluorescence resonance energy transfer owing to a large overlap between upconversion emission and rose-bengal hexanic acid absorption (UCNPs-RBHA). At the same time, the UCNPs-RBHA conjugated with platinum (IV) and polyethylene glycol possesses high cell apoptosis for the CT26 cells due to high endocytosis. The UCL and MR imaging, temperature sensing, and strong antitumor effect based on the synergetic therapy of PDT and chemotherapy are achieved on the single nanoparticles.

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Section snippets

Cells and animals

CT26 cells (murine colon carcinoma cell line) were used to test, which bought from the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. The cells were cultured in RPMI-1640 medium (1640, GIBCO), which including 10% fetal bovine serum (FBS, Kang Yuan Biology), 100 units mL−1 penicillin, and 100 μg mL−1 streptomycin (Sigma) in an atmosphere of 5% CO2 at 37 °C. Balb/c mice (25–30 g) were purchased from Center for Experimental Animals, Jilin University (Changchun, China).

Sample preparation and characterization

CaF2, CaF2@NaGdF4 and CaF2@NaGdF4@NaGdF4 UCNPs are obtained by solvothermal process.30 The TEM images of them are shown in Figure 1, AC, it can be found that the UCNPs are homogeneous and the average sizes are 8.6, 10.0, and 13.6 nm, respectively. The size of sample is smaller than common rare earth fluoride by same method (same ratio between OA and ODE), such as NaYF4.31., 32. In addition, the particle size is related to charge compensation effects while calcium ions are replaced by rare

Discussion

In this study, the small-sized and abundant-fluorescent CaF2: Yb3+/Er3+ UCNPs are achieved by solvothermal route. In particular, the charge compensation effects and core-shell structure have made a great contribution for it, respectively. After coated by PEI, the RBHA and DSP can be combined with UCNPs by the dehydration condensation between amine and carboxyl group, which lays the foundation for the realization of dual functions of PDT and chemotherapy. In addition, the temperature test in

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    Conflicts of Interest: the authors declare no conflicts of interest.

    Acknowledgements: This project is financially supported by Science and Technology Cooperation Project between Chinese and Australian Governments (2017YFE0132300), the National Natural Science Foundation of China (Grant Nos. NSFC 51720105015, 11874182, 51672269, 51772124, 51922097, and 51872282), Science and Technology Development Planning Project of Jilin Province (Grant 20170101188JC, and 20180520163JH), Youth Innovation Promotion Association of CAS (Grant No. 2017273), Overseas, Hong Kong & Macao Scholars Collaborated Researching Fund (Grant No. 21728101), Science and Technology Project of the 13th Five-Year Plan of Jilin Provincial Department of Education (No. JJKH20190179KJ) and provincial industrial innovation in Jilin Province (No. 2018C043-4).

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