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Magneto-fluorescent core-shell supernanoparticles.

Chen O, Riedemann L, Etoc F, Herrmann H, Coppey M, Barch M, Farrar CT, Zhao J, Bruns OT, Wei H, Guo P, Cui J, Jensen R, Chen Y, Harris DK, Cordero JM, Wang Z, Jasanoff A, Fukumura D, Reimer R, Dahan M, Jain RK, Bawendi MG - Nat Commun (2014)

Bottom Line: A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality.We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked.Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.

ABSTRACT
Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magneto-fluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle 'core', which is fully surrounded by a 'shell' of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.

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Silica-CS-SPs in biological applicationsa, Force applied to individual silica-CS-SPs as a function of the distance from the magnetic tip (Supplementary Movie 6). A power law (red curve) fits the data. b, Tracking of individual silica-CS-SPs during their manipulation inside a Cos7 cell (Supplementary Movie 4). Positions along each trajectory are color-coded according to the time. Scale bar is 15 μm. c, Left: Fluorescence imaging of individual silica-CS-SPs (yellow) in the dashed line region of panel b and before the manipulation. The barycenter of the individual localizations is shown as a yellow cross. Right: superposition of the silica-CS-SPs fluorescence after 2 minutes (red), the barycenter of the individual localizations is shown as a red cross. d, Left: Transmission picture of a Hela cell in which silica-CS-SPs have been microinjected. By bringing the magnetic tip in and out (blue bars), a reversible accumulation of silica-CS-SPs (yellow region) can be created at the cell periphery (indicated by red dashed line), in the direction of the magnetic tip (Supplementary Movie 5). Scale bar is 15 μm. Methoxy-polyethylene-glycol silane (mPEG-silane, MW5000) functionalized silica-CS-SPs (200μL, 2mg/mL) were intravenously injected into C3H mice bearing brain metastasis of a murine mammary carcinoma (MCaIV) with a cranial window model. Intravital multiphoton microscopy through the cranial window was carried out at different time point: pre-injection (e), 4-hour post-injection (f), and 24-hour post-injection (g). Scale bar is 150 μm. Images from red and green channels are shown in small panels (top: red channel, bottom: green channel). Green emission signals are generated from a blood vessel tracer (Fluorescein isothiocyanate–dextran, FITC-Dextran) and red emission signals are generated by mPEG functionalized silica-CS-SPs. In vivo T2-weighted magnetic resonance images of pre- (h) and 24-hour post- (i) injection of mPEG-silane functionalized silica-CS-SPs. 24-hour post-injection image show clear tumor visualization (denoted by the red-dash line). Scale bar is 3 mm. j, The corresponding T2 relaxation (relax.) time fitting results for the tumor region at time points of pre-injection (Pre., blue bar) and 24-hour post-injection (Post., red bar). n = 5 mice, *** P < 0.001 (Student’s t test).
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Figure 4: Silica-CS-SPs in biological applicationsa, Force applied to individual silica-CS-SPs as a function of the distance from the magnetic tip (Supplementary Movie 6). A power law (red curve) fits the data. b, Tracking of individual silica-CS-SPs during their manipulation inside a Cos7 cell (Supplementary Movie 4). Positions along each trajectory are color-coded according to the time. Scale bar is 15 μm. c, Left: Fluorescence imaging of individual silica-CS-SPs (yellow) in the dashed line region of panel b and before the manipulation. The barycenter of the individual localizations is shown as a yellow cross. Right: superposition of the silica-CS-SPs fluorescence after 2 minutes (red), the barycenter of the individual localizations is shown as a red cross. d, Left: Transmission picture of a Hela cell in which silica-CS-SPs have been microinjected. By bringing the magnetic tip in and out (blue bars), a reversible accumulation of silica-CS-SPs (yellow region) can be created at the cell periphery (indicated by red dashed line), in the direction of the magnetic tip (Supplementary Movie 5). Scale bar is 15 μm. Methoxy-polyethylene-glycol silane (mPEG-silane, MW5000) functionalized silica-CS-SPs (200μL, 2mg/mL) were intravenously injected into C3H mice bearing brain metastasis of a murine mammary carcinoma (MCaIV) with a cranial window model. Intravital multiphoton microscopy through the cranial window was carried out at different time point: pre-injection (e), 4-hour post-injection (f), and 24-hour post-injection (g). Scale bar is 150 μm. Images from red and green channels are shown in small panels (top: red channel, bottom: green channel). Green emission signals are generated from a blood vessel tracer (Fluorescein isothiocyanate–dextran, FITC-Dextran) and red emission signals are generated by mPEG functionalized silica-CS-SPs. In vivo T2-weighted magnetic resonance images of pre- (h) and 24-hour post- (i) injection of mPEG-silane functionalized silica-CS-SPs. 24-hour post-injection image show clear tumor visualization (denoted by the red-dash line). Scale bar is 3 mm. j, The corresponding T2 relaxation (relax.) time fitting results for the tumor region at time points of pre-injection (Pre., blue bar) and 24-hour post-injection (Post., red bar). n = 5 mice, *** P < 0.001 (Student’s t test).

Mentions: One of the persistent challenges in cell biology is to understand how a series of biomolecular activities can be integrated and modulated in the intracellular space. Several recent experiments have shown how magnetic nanoparticles could be used as actuators for remote control of signaling processes at the single cell level with subcellular resolution40, 41. Yet, experimental failure is quite common, mainly due to particle polydispersities in size and magnetic content that not only make microinjection of nanoparticles difficult, but also render intracellular manipulation fragile due to the viscoelasticity of the cytoplasm. As a consequence, there is a pressing need for the fabrication of nanoparticles that have a small and uniform size but still show strong magnetism for efficient response, and are also highly fluorescent for monitoring their intracellular spatial distribution. The specifications of our silica-CS-SPs meet all these requirements. Given a particle diameter of ~100 nm, forces on the order of 1 pN, similar to the force generated by a molecular motor42, can be generated with a magnetic tip (Fig. 4a). These forces were sufficient to efficiently manipulate silica-CS-SPs across whole cells within minutes (Fig. 4b–d and Supplementary Movie 4 and 5). The movement of the silica-CS-SPs appears to be only marginally hindered by the cytoplasmic meshwork (Fig. 4b–d). The silica-CS-SPs are bright enough that their individual trajectories can be tracked with great accuracy (a pointing accuracy of ~15nm) throughout their transport within the cytoplasm (Fig. 4b and c). The key for success and reproducibility of these experiments is the superior homogeneity in both particle size and magnetic content of these silica-CS-SPs. We thus expect silica-CS-SPs, once decorated with targeting or signaling molecules, to constitute a powerful platform for the magnetic control/manipulation of intracellular processes.


Magneto-fluorescent core-shell supernanoparticles.

Chen O, Riedemann L, Etoc F, Herrmann H, Coppey M, Barch M, Farrar CT, Zhao J, Bruns OT, Wei H, Guo P, Cui J, Jensen R, Chen Y, Harris DK, Cordero JM, Wang Z, Jasanoff A, Fukumura D, Reimer R, Dahan M, Jain RK, Bawendi MG - Nat Commun (2014)

Silica-CS-SPs in biological applicationsa, Force applied to individual silica-CS-SPs as a function of the distance from the magnetic tip (Supplementary Movie 6). A power law (red curve) fits the data. b, Tracking of individual silica-CS-SPs during their manipulation inside a Cos7 cell (Supplementary Movie 4). Positions along each trajectory are color-coded according to the time. Scale bar is 15 μm. c, Left: Fluorescence imaging of individual silica-CS-SPs (yellow) in the dashed line region of panel b and before the manipulation. The barycenter of the individual localizations is shown as a yellow cross. Right: superposition of the silica-CS-SPs fluorescence after 2 minutes (red), the barycenter of the individual localizations is shown as a red cross. d, Left: Transmission picture of a Hela cell in which silica-CS-SPs have been microinjected. By bringing the magnetic tip in and out (blue bars), a reversible accumulation of silica-CS-SPs (yellow region) can be created at the cell periphery (indicated by red dashed line), in the direction of the magnetic tip (Supplementary Movie 5). Scale bar is 15 μm. Methoxy-polyethylene-glycol silane (mPEG-silane, MW5000) functionalized silica-CS-SPs (200μL, 2mg/mL) were intravenously injected into C3H mice bearing brain metastasis of a murine mammary carcinoma (MCaIV) with a cranial window model. Intravital multiphoton microscopy through the cranial window was carried out at different time point: pre-injection (e), 4-hour post-injection (f), and 24-hour post-injection (g). Scale bar is 150 μm. Images from red and green channels are shown in small panels (top: red channel, bottom: green channel). Green emission signals are generated from a blood vessel tracer (Fluorescein isothiocyanate–dextran, FITC-Dextran) and red emission signals are generated by mPEG functionalized silica-CS-SPs. In vivo T2-weighted magnetic resonance images of pre- (h) and 24-hour post- (i) injection of mPEG-silane functionalized silica-CS-SPs. 24-hour post-injection image show clear tumor visualization (denoted by the red-dash line). Scale bar is 3 mm. j, The corresponding T2 relaxation (relax.) time fitting results for the tumor region at time points of pre-injection (Pre., blue bar) and 24-hour post-injection (Post., red bar). n = 5 mice, *** P < 0.001 (Student’s t test).
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Figure 4: Silica-CS-SPs in biological applicationsa, Force applied to individual silica-CS-SPs as a function of the distance from the magnetic tip (Supplementary Movie 6). A power law (red curve) fits the data. b, Tracking of individual silica-CS-SPs during their manipulation inside a Cos7 cell (Supplementary Movie 4). Positions along each trajectory are color-coded according to the time. Scale bar is 15 μm. c, Left: Fluorescence imaging of individual silica-CS-SPs (yellow) in the dashed line region of panel b and before the manipulation. The barycenter of the individual localizations is shown as a yellow cross. Right: superposition of the silica-CS-SPs fluorescence after 2 minutes (red), the barycenter of the individual localizations is shown as a red cross. d, Left: Transmission picture of a Hela cell in which silica-CS-SPs have been microinjected. By bringing the magnetic tip in and out (blue bars), a reversible accumulation of silica-CS-SPs (yellow region) can be created at the cell periphery (indicated by red dashed line), in the direction of the magnetic tip (Supplementary Movie 5). Scale bar is 15 μm. Methoxy-polyethylene-glycol silane (mPEG-silane, MW5000) functionalized silica-CS-SPs (200μL, 2mg/mL) were intravenously injected into C3H mice bearing brain metastasis of a murine mammary carcinoma (MCaIV) with a cranial window model. Intravital multiphoton microscopy through the cranial window was carried out at different time point: pre-injection (e), 4-hour post-injection (f), and 24-hour post-injection (g). Scale bar is 150 μm. Images from red and green channels are shown in small panels (top: red channel, bottom: green channel). Green emission signals are generated from a blood vessel tracer (Fluorescein isothiocyanate–dextran, FITC-Dextran) and red emission signals are generated by mPEG functionalized silica-CS-SPs. In vivo T2-weighted magnetic resonance images of pre- (h) and 24-hour post- (i) injection of mPEG-silane functionalized silica-CS-SPs. 24-hour post-injection image show clear tumor visualization (denoted by the red-dash line). Scale bar is 3 mm. j, The corresponding T2 relaxation (relax.) time fitting results for the tumor region at time points of pre-injection (Pre., blue bar) and 24-hour post-injection (Post., red bar). n = 5 mice, *** P < 0.001 (Student’s t test).
Mentions: One of the persistent challenges in cell biology is to understand how a series of biomolecular activities can be integrated and modulated in the intracellular space. Several recent experiments have shown how magnetic nanoparticles could be used as actuators for remote control of signaling processes at the single cell level with subcellular resolution40, 41. Yet, experimental failure is quite common, mainly due to particle polydispersities in size and magnetic content that not only make microinjection of nanoparticles difficult, but also render intracellular manipulation fragile due to the viscoelasticity of the cytoplasm. As a consequence, there is a pressing need for the fabrication of nanoparticles that have a small and uniform size but still show strong magnetism for efficient response, and are also highly fluorescent for monitoring their intracellular spatial distribution. The specifications of our silica-CS-SPs meet all these requirements. Given a particle diameter of ~100 nm, forces on the order of 1 pN, similar to the force generated by a molecular motor42, can be generated with a magnetic tip (Fig. 4a). These forces were sufficient to efficiently manipulate silica-CS-SPs across whole cells within minutes (Fig. 4b–d and Supplementary Movie 4 and 5). The movement of the silica-CS-SPs appears to be only marginally hindered by the cytoplasmic meshwork (Fig. 4b–d). The silica-CS-SPs are bright enough that their individual trajectories can be tracked with great accuracy (a pointing accuracy of ~15nm) throughout their transport within the cytoplasm (Fig. 4b and c). The key for success and reproducibility of these experiments is the superior homogeneity in both particle size and magnetic content of these silica-CS-SPs. We thus expect silica-CS-SPs, once decorated with targeting or signaling molecules, to constitute a powerful platform for the magnetic control/manipulation of intracellular processes.

Bottom Line: A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality.We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked.Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.

ABSTRACT
Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magneto-fluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle 'core', which is fully surrounded by a 'shell' of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.

Show MeSH
Related in: MedlinePlus