tumor passive uptake of MFNP nanoparticles is likely due to the enhanced permeability and retention (EPR)effect of cancerous tumors and may be utilized for in vivo imaging-guided photothermal/magnetic hyperthermia ablation of tumors in the future.
Finally,MFNPs were also used for multimodal mapping of lymph nodes in mice.As local lymphatic drainage is an important route for the metastasis of cancer cells,identifica-tion of the sentinel lymph nodes has become a common staging procedure for cancers.[9,32]We intracutaneously injected PEG–MFNPs (15m L,2.5mg mL à1)into one rear paw of a mouse to monitor the lymphatic drainages in the lower trunk.The primary lymph node to which MFNPs migrated by lymphatic drainage was visualized by in vivo
UCL imaging two hours after injection (Figure 5g,Support-ing Information Figure S17).The dark spot observed in MR images was also unambiguously assigned to the brachial lymph node on the basis of the detailed anatomical informa-tion provided by MRI (Figure 5h,Supporting Information Figure S15).
In summary,MFNPs based on UCNPs with combined optical and magnetic properties are synthesized via a simple LBL self-assembly strategy.PEG-ylated MFNPs can be used for in vitro targeted UCL,MR,and dark-field imaging;for molecular and magnetic targeted PTT of cancer cells;and as a contrast agent for in vivo dual-modal UCL/MR imaging in mice.Our work shows a facile method to prepare a novel class of multimodality imaging nanoprobes with a wide range of useful functionalities.The UCNP is the core and substrate of this MFNP system and offers UCL emission for optical imaging.IONPs afford the nanocomposites superparamag-netic properties useful in T 2-weighted MR imaging and magnetic targeted therapy and also serve as a “buffer”layer between the luminescent UCNP core and the outside gold shell to reduce the UCL quenching effect.The gold shell grown on top of the IONP layer allows easy chemical functionalization of MFNPs through the widely applied gold–thiol chemistry and also exhibits surface plasmon resonance in the visible and NIR regions,which can be utilized in PTT and dark-field scattering imaging as well as possibly for photoacoustic and Raman imaging.[33,34]The multimodal UCL optical/MR imaging could combine the advantages of each single imaging tool for enhanced sensi-tivity and improved tissue penetration.The dual molecular/magnetic targeting may allow more selective and localized therapies.Although further work may be needed to optimize their sizes and surface coatings for reduced RES uptake,as well as to demonstrate the in vivo molecular targeted imaging and photothermal therapy using MFNPs,the UCNP-based MFNPs developed herein are promising for many applica-tions in biomedicine,including multimodality imaging,cell tracking,and imaging-guided novel targeted cancer therapies.
Received:February 27,2011Revised:April 27,2011
Published online:June 28,2011
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Keywords:imaging agents ·multifunctional systems ·nanoparticles ·photothermal therapy ·upconversion
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Figure 5.Dual-modal UCL/MR in vivo imaging.a–c)The bright field (a),UCL (b),and merged (c)images of a KB tumor-bearing mouse one hour after intravenous injection of PEG–MFNP.Strong UCL signals were observed from the liver and tumor sites (arrow)of the mouse.d)Ex vivo UCL imaging showing accumulation of MNFPs in the liver,spleen,tumor,bone,and lung of the injected mouse at 24h post injection.UCL signals from other organs were barely detectable.e,f)T 2-weighted images of KB-tumor bearing nude mice with (e)and without (f)injection of MFNPs.Obvious darkening contrast was shown in the mouse liver and tumor.g,h)Multimodal UCL (g)and MR (h)imaging for in vivo lymphangiography mapping using MFNPs.MR images were taken before (left)and after (right)injection of
MFNPs.
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2011Wiley-VCH Verlag GmbH &Co.KGaA,Weinheim
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