Chenjie Xu

Self-illuminating quantum dot conjugates for in vivo imaging.

Fluorescent semiconductor quantum dots hold great potential for molecular imaging in vivo. However, the utility of existing quantum dots for in vivo imaging is limited because they require excitation from external illumination sources to fluoresce, which results in a strong autofluorescence background and a paucity of excitation light at nonsuperficial locations. Here we present quantum dot conjugates that luminesce by bioluminescence resonance energy transfer in the absence of external excitation. The conjugates are prepared by coupling carboxylate-presenting quantum dots to a mutant of the bioluminescent protein Renilla reniformis luciferase. We show that the conjugates emit long-wavelength (from red to near-infrared) bioluminescent light in cells and in animals, even in deep tissues, and are suitable for multiplexed in vivo imaging. Compared with existing quantum dots, self-illuminating quantum dot conjugates have greatly enhanced sensitivity in small animal imaging, with an in vivo signal-to-background ratio of > 103 for 5 pmol of conjugate.

PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles

The purpose of this study was to develop a bifunctional iron oxide (IO) nanoparticle probe for PET and MRI scans of tumor integrin αvβ3 expression. Methods: Polyaspartic acid (PASP)–coated IO (PASP-IO) nanoparticles were synthesized using a coprecipitation method, and particle size and magnetic properties were measured. A phantom study was used to assess the efficacy of PASP-IO as a T2-weighted MRI contrast agent. PASP-IO nanoparticles with surface amino groups were coupled to cyclic arginine-glycine-aspartic (RGD) peptides for integrin αvβ3 targeting and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″,-tetraacetic acid (DOTA) chelators for PET after labeling with 64Cu. IO nanoparticle conjugates were further tested in vitro and in vivo to determine receptor targeting efficacy and feasibility for dual PET/MRI. Results: PASP-IO nanoparticles made by single-step reaction have a core size of 5 nm with a hydrodynamic diameter of 45 ± 10 nm. The saturation magnetization of PASP-IO nanoparticles is about 117 emu/g of iron, and the measured r2 and r2* are 105.5 and 165.5 (s·mM)−1, respectively. A displacement competitive binding assay indicates that DOTA-IO-RGD conjugates bound specifically to integrin αvβ3 in vitro. Both small-animal PET and T2-weighted MRI show integrin-specific delivery of conjugated RGD-PASP-IO nanoparticles and prominent reticuloendothelial system uptake. Conclusion: We have successfully developed an IO-based nanoprobe for simultaneous dual PET and MRI of tumor integrin expression. The success of this bifunctional imaging approach may allow for earlier tumor detection with a high degree of accuracy and provide further insight into the molecular mechanisms of cancer.

Porous Hollow Fe3O4 Nanoparticles for Targeted Delivery and Controlled Release of Cisplatin

We report a new approach to cisplatin storage and release using porous hollow nanoparticles (PHNPs) of Fe(3)O(4). We prepared the PHNPs by controlled oxidation of Fe NPs at 250 degrees C followed by acid etching. The opening pores ( approximately 2-4 nm) facilitated the cisplatin diffusion into the cavity of the hollow structure. The porous shell was stable in neutral or basic physiological conditions, and cisplatin escape from the cavity through the same pores was a diffusion-controlled slow process with t(1/2) = 16 h. However, in low pH (<6) conditions, the pores were subject to acidic etching, resulting in wider pore gaps and faster release of cisplatin with t(1/2) < 4 h. Once coupled with Herceptin to the surface, the cisplatin-loaded hollow NPs could target to breast cancer SK-BR-3 cells with IC(50) reaching 2.9 muM, much lower than 6.8 muM needed for free cisplatin. Our model experiments indicate that the low pH-responsive PHNPs of Fe(3)O(4) can be exploited as a cisplatin delivery vehicle for target-specific therapeutic applications.

Ultrasmall c(RGDyK)-Coated Fe3O4 Nanoparticles and Their Specific Targeting to Integrin αvβ3-Rich Tumor Cells

We report a direct synthesis of ultrasmall c(RGDyK) peptide-coated Fe3O4 NPs (<10 nm in hydrodynamic diameter) and demonstrate their in vivo tumor-specific targeting capability. The Fe3O4 NPs are synthesized by thermal decomposition of iron pentacarbonyl in the presence of 4-methylcatechol (4-MC), and the peptide is coupled to the nanoparticles through 4-MC via Mannich reaction. The c(RGDyK)-MC-Fe3O4 NPs have an overall diameter of approximately 8.4 nm and are stable in physiological conditions. When administrated intravenously, these c(RGDyK)-MC-Fe3O4 NPs accumulate preferentially in the integrin alphavbeta3-rich tumor area, which are readily tracked by MRI.

Dumbbell-Like Au-Fe3O4 Nanoparticles for Target-Specific Platin Delivery

Dumbbell-like Au-Fe(3)O(4) nanoparticles (NPs) were made and coupled with Herceptin and a platin complex. The platin-Au-Fe(3)O(4)-Herceptin NPs act as a target-specific nanocarriers for delivery of platin into Her2-positive breast cancer cells (Sk-Br3) with strong therapeutic effects. The conjugate has a half-maximal inhibitory concentration (IC(50)) toward Sk-Br3 cells of 1.76 microg of Pt/mL, which is lower than that needed for cisplatin (3.5 microg/mL). The work demonstrates that the dumbbell-like Au-Fe(3)O(4) NPs are promising nanocarriers for highly sensitive diagnostic and therapeutic applications.

Biofunctional magnetic nanoparticles for protein separation and pathogen detection

Recent successful syntheses of monodispersed magnetic nanoparticles have offered a unique opportunity to control and probe biological interactions using magnetic force. This paper highlights a general strategy to generate biofunctional magnetic nanoparticles, illustrates applications for these nanoparticles in protein separation and pathogen detection, and analyzes the high sensitivity and high selectivity achieved by this system.

New forms of superparamagnetic nanoparticles for biomedical applications.

Magnetic nanoparticles (MNPs) based on iron oxide, especially magnetite (Fe3O4), have been explored as sensitive probes for magnetic resonance imaging and therapeutic applications. Such application potentials plus the need to achieve high efficiency and sensitivity have motivated the search for new forms of superparamagnetic NPs with additional chemical and physical functionalities. This review summarizes the latest development of high moment MNPs, multifunctional MNPs, and porous hollow MNPs for biosensing, molecular imaging, and drug delivery applications.

Accelerating the Translation of Nanomaterials in Biomedicine

Due to their size and tailorable physicochemical properties, nanomaterials are an emerging class of structures utilized in biomedical applications. There are now many prominent examples of nanomaterials being used to improve human health, in areas ranging from imaging and diagnostics to therapeutics and regenerative medicine. An overview of these examples reveals several common areas of synergy and future challenges. This Nano Focus discusses the current status and future potential of promising nanomaterials and their translation from the laboratory to the clinic, by highlighting a handful of successful examples.

pH Controlled Release of Chromone from Chromone-Fe3O4 Nanoparticles

We report a new strategy for coupling chromone to Fe3O4 nanoparticles. The chromone-Fe3O4 NP conjugate shows a dramatic increase in chromone solubility in cell culture medium from less than 2.5 to 633 microg/ml, leading to the enhanced chromone uptake by HeLa cells. Chromone can be released at low pH and as a result, the chromone-Fe3O4 conjugate is much more efficient in inhibiting the HeLa cell proliferation. Such chromone-Fe3O4 NPs are promising as a powerful multifunctional delivery system for both chromone-based diagnostic and therapeutic applications.

FePt nanoparticles as an Fe reservoir for controlled Fe release and tumor inhibition.

Chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) show the controlled release of Fe in low pH solution. The released Fe catalyzes H(2)O(2) decomposition into reactive oxygen species within cells, causing fast oxidation and deterioration of cellular membranes. Functionalized with luteinizing hormone-releasing hormone (LHRH) peptide via phospholipid, the fcc-FePt NPs can bind preferentially to the human ovarian cancer cell line (A2780) that overexpresses LHRH receptors and exhibit high toxicity to these tumor cells. In contrast, the fcc-FePt NPs pre-etched in the low pH (4.8) buffer solution show nonappreciable cytotoxicity. The work demonstrates that fcc-FePt NPs may function as a new type of agent for controlled cancer therapy.