Co-reporter:Xucheng Luo, Zhi Li, Ganglin Wang, Xuewen He, Xiaoqin Shen, Quanhong Sun, Li Wang, Renye Yue, and Nan Ma
ACS Applied Materials & Interfaces October 4, 2017 Volume 9(Issue 39) pp:33624-33624
Publication Date(Web):September 15, 2017
DOI:10.1021/acsami.7b09420
The use of cancer-relevant microRNA molecules as endogenous drug release stimuli is promising for personalized cancer treatment yet remains a great challenge because of their low abundance. Herein, we report a new type of microRNA-catalyzed drug release system based on DNA-programmed gold nanoparticle (GNP)–quantum dot (QD) complex. We show that a trace amount of miRNA-21 molecules could specifically catalyze the disassembly of doxorubicin (Dox)-loaded GNP–QDs complex through entropy driven process, during which the Dox-intercalating sites are destructed for drug release. This catalytic reaction could proceed both in fixed cells and live cells with miRNA-21 overexpression. Dox molecules could be efficiently released in the cells and translocate to cell nuclei. QD photoluminescence is simultaneously activated during catalytic disassembly process, thus providing a reliable feedback for microRNA-triggered drug release. The GNP–QDs–Dox complex exhibits much higher drug potency than free Dox molecules, and therefore represents a promising platform for accurate and effective cancer cell treatment.Keywords: catalysis; doxorubicin; microRNA; quantum dot; therapy;
Co-reporter:Zhi Li, Xuewen He, Xucheng Luo, Li Wang, and Nan Ma
Analytical Chemistry 2016 Volume 88(Issue 19) pp:9355
Publication Date(Web):September 20, 2016
DOI:10.1021/acs.analchem.6b02864
Inorganic nanocrystals, such as quantum dots (QDs), hold great promise as molecular imaging contrast agents because of their superior optical properties. However, the molecular imaging sensitivity of these probes is far from optimized due to the lack of efficient and general method for molecular engineering of nanocrystal into effective bioprobes for signal-amplified imaging. Herein, we develop a strategy to boost the molecular imaging sensitivity of QDs over the limit by copolymerizing QDs and cell-binding aptamers into linear QD-aptamer polymers (QAPs) through DNA-programmed hybridization chain reaction. We show that the cancer cells treated with QAPs exhibit much stronger photoluminescence (PL) signal than those treated with QD-aptamer monomers (QAMs) because of multivalent binding and multi-QD-based signal amplification. The enhanced cell binding and imaging capacity of QAPs significantly improves imaging-based discrimination between different cancer cell types. This approach adds a new dimension for engineering inorganic nanoparticles into effective bioprobes for biomedical applications.
Co-reporter:Xuewen He;Tao Zeng;Zhi Li;Ganglin Wang ; Nan Ma
Angewandte Chemie International Edition 2016 Volume 55( Issue 9) pp:
Publication Date(Web):
DOI:10.1002/anie.201600456
Co-reporter:Xuewen He;Tao Zeng;Zhi Li;Ganglin Wang ; Nan Ma
Angewandte Chemie International Edition 2016 Volume 55( Issue 9) pp:3073-3076
Publication Date(Web):
DOI:10.1002/anie.201509726
Abstract
Molecular imaging is an essential tool for disease diagnostics and treatment. Direct imaging of low-abundance nucleic acids in living cells remains challenging because of the relatively low sensitivity and insufficient signal-to-background ratio of conventional molecular imaging probes. Herein, we report a class of DNA-templated gold nanoparticle (GNP)–quantum dot (QD) assembly-based probes for catalytic imaging of cancer-related microRNAs (miRNA) in living cells with signal amplification capacity. We show that a single miRNA molecule could catalyze the disassembly of multiple QDs with the GNP through a DNA-programmed thermodynamically driven entropy gain process, yielding significantly amplified QD photoluminescence (PL) for miRNA imaging. By combining the robust PL of QDs with the catalytic amplification strategy, three orders of magnitude improvement in detection sensitivity is achieved in comparison with non-catalytic imaging probe, which enables facile and accurate differentiation between cancer cells and normal cells by miRNA imaging in living cells.
Co-reporter:Xuewen He;Tao Zeng;Zhi Li;Ganglin Wang ; Nan Ma
Angewandte Chemie 2016 Volume 128( Issue 9) pp:3125-3128
Publication Date(Web):
DOI:10.1002/ange.201509726
Abstract
Molecular imaging is an essential tool for disease diagnostics and treatment. Direct imaging of low-abundance nucleic acids in living cells remains challenging because of the relatively low sensitivity and insufficient signal-to-background ratio of conventional molecular imaging probes. Herein, we report a class of DNA-templated gold nanoparticle (GNP)–quantum dot (QD) assembly-based probes for catalytic imaging of cancer-related microRNAs (miRNA) in living cells with signal amplification capacity. We show that a single miRNA molecule could catalyze the disassembly of multiple QDs with the GNP through a DNA-programmed thermodynamically driven entropy gain process, yielding significantly amplified QD photoluminescence (PL) for miRNA imaging. By combining the robust PL of QDs with the catalytic amplification strategy, three orders of magnitude improvement in detection sensitivity is achieved in comparison with non-catalytic imaging probe, which enables facile and accurate differentiation between cancer cells and normal cells by miRNA imaging in living cells.
Co-reporter:Xuewen He;Tao Zeng;Zhi Li;Ganglin Wang ; Nan Ma
Angewandte Chemie 2016 Volume 128( Issue 9) pp:
Publication Date(Web):
DOI:10.1002/ange.201600456
Co-reporter:Dan Wu, Guofen Song, Zhi Li, Tao Zhang, Wei Wei, Muzi Chen, Xuewen He and Nan Ma
Chemical Science 2015 vol. 6(Issue 7) pp:3839-3844
Publication Date(Web):08 Apr 2015
DOI:10.1039/C4SC03894K
Ideal theranostics should possess directly correlated imaging and therapy modalities that could be simultaneously activated in the disease site to generate high imaging contrast and therapeutic efficacy with minimal side effects. However, so far it still remains challenging to engineer all these characteristics into a single theranostic probe. Herein, we report a new type of photosensitizer (PS)-derived “two-dimensional” molecular beacon (TMB) that could be specifically activated within tumor cells to exhibit both high imaging contrast and therapeutic efficacy that outperforms conventional photosensitizers for cancer theranostics. The TMB is constructed by integrating a photosensitizer (chlorin e6 (Ce6)), a quantum dot (QD), and a dark quencher (BHQ3) into a hairpin DNA molecule to generate multiple synergistic FRET modes. The imaging modality and therapy modality, which are mediated by FRET between the QD and BHQ3 and FRET between the QD and Ce6 respectively, are interconnected within the TMB and could be simultaneously activated by tumor mRNA molecules. We show that highly effective cancer imaging and therapy could be achieved for cancer cell lines and xenografted tumor models. The reported TMB represents an unprecedented theranostic platform for intelligent cancer theranostics.
Co-reporter:Tao Zeng, Tao Zhang, Wei Wei, Zhi Li, Dan Wu, Li Wang, Jun Guo, Xuewen He, and Nan Ma
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 22) pp:11849
Publication Date(Web):May 13, 2015
DOI:10.1021/acsami.5b01446
Protease represents an important class of biomarkers for disease diagnostics and drug screening. Conventional fluorescence-based probes for in vivo protease imaging suffer from short excitation wavelengths and poor photostability. Upconversion nanoparticles (UCNPs) hold great promise for biosensing and bioimaging because of their deep-tissue excitability, robust photostability, and minimal imaging background. However, producing highly stable and compact biofunctionalized UCNP probes with optimal bioresponsivity for in vivo imaging of protease activities still remains challenging and has not been previously demonstrated. Herein, we report facile preparation of highly compact and stable biofunctionalized UCNPs through peptide-mediated phase transfer for high-sensitive detection of protease in vitro and in vivo. We demonstrate that the polyhistidine-containing chimeric peptides could displace oleic acid molecules capped on UCNPs synthesized in organic solvents and, thereby, directly transfer UCNPs from the chloroform phase to the water phase. The resulting UCNPs possess high stability, programmable surface properties, and a compact coating layer with minimized thickness for efficient luminescence resonance energy transfer (LRET). On the basis of this strategy, we prepared LRET-based UCNP probes with optimal bioresponsivity for in vitro high-sensitive detection of trypsin and in vivo imaging of apoptosis for chemotherapy efficacy evaluation. The reported strategy could be extended to construct a variety of peptide-functionalized UCNPs for various biomedical applications.Keywords: biosensing; in vivo imaging; peptide; phase transfer; protease; upconversion nanoparticle;
Co-reporter:Xuewen He and Nan Ma
Analytical Chemistry 2014 Volume 86(Issue 7) pp:3676
Publication Date(Web):March 16, 2014
DOI:10.1021/ac500590d
Development of rapid, sensitive, and cost-effective DNA detection is of great significance to meet the growing demand of disease diagnostics. Herein, we report a new general strategy for label-free sensitive in-solution DNA detection using quantum dot (QD) doping-induced photoluminescence as a fluorogenic reporter system. The dopant mercury (Hg(II)) ions are initially sequestered in the hairpin-structured probe through T–Hg2+–T mismatch formation. Upon hybridization with the DNA target, the hairpin is disrupted and Hg2+ ions are released and incorporated into ZnSe QDs, leading to a dopant-specific emission peak at 560 nm for DNA detection. Unlike the other methods, this method does not require any chemical modification of the DNA probe. It could provide high signal-to-noise ratio, robust single-base mismatch discrimination capability, and 3 orders of magnitude lower limit of detection (LOD) than the traditional molecular beacon (MB)-based fluorescence spectroscopy without any type of amplification. The method could be used for the detection of a variety of clinical significant DNA targets containing single mutations. To the best of our knowledge, this is the first study on applying chemical transformation of inorganic nanostructures to sensitive DNA detection.
Co-reporter:Wei Wei;Xuewen He ; Nan Ma
Angewandte Chemie International Edition 2014 Volume 53( Issue 22) pp:5573-5577
Publication Date(Web):
DOI:10.1002/anie.201400428
Abstract
Quantum dots (QDs) hold great promise for the molecular imaging of cancer because of their superior optical properties. Although cell-surface biomarkers can be readily imaged with QDs, non-invasive live-cell imaging of critical intracellular cancer markers with QDs is a great challenge because of the difficulties in the automatic delivery of QD probes to the cytosol and the ambiguity of intracellular targeting signals. Herein, we report a new type of DNA-templated heterobivalent QD nanoprobes with the ability to target and image two spatially isolated cancer markers (nucleolin and mRNA) present on the cell surface and in the cell cytosol. Bypassing endolysosomal sequestration, this type of QD nanoprobes undergo macropinocytosis following the nucleolin targeting and then translocate to the cytosol for mRNA targeting. Fluorescence resonance energy transfer (FRET) based confocal microscopy enables unambiguous signal deconvolution of mRNA-targeted QD nanoprobes inside cancer cells.
Co-reporter:Xuewen He;Zhi Li;Muzi Chen ; Nan Ma
Angewandte Chemie International Edition 2014 Volume 53( Issue 52) pp:14447-14450
Publication Date(Web):
DOI:10.1002/anie.201408479
Abstract
Despite the widespread use of quantum dots (QDs) for biosensing and bioimaging, QD-based bio-interfaceable and reconfigurable molecular computing systems have not yet been realized. DNA-programmed dynamic assembly of multi-color QDs is presented for the construction of a new class of fluorescence resonance energy transfer (FRET)-based QD computing systems. A complete set of seven elementary logic gates (OR, AND, NOR, NAND, INH, XOR, XNOR) are realized using a series of binary and ternary QD complexes operated by strand displacement reactions. The integration of different logic gates into a half-adder circuit for molecular computation is also demonstrated. This strategy is quite versatile and straightforward for logical operations and would pave the way for QD-biocomputing-based intelligent molecular diagnostics.
Co-reporter:Xuewen He, Nan Ma
Colloids and Surfaces B: Biointerfaces 2014 Volume 124() pp:118-131
Publication Date(Web):1 December 2014
DOI:10.1016/j.colsurfb.2014.06.002
•Overview of novel QD synthetic methods.•Overview of novel type of QDs.•Overview of QDs for biosensing, bioimaging, and therapy applications.During the past ten years significant advances have been achieved in quantum dot (QD) research field. The new synthetic methods and the discovery of new types of QDs have enabled a variety of new applications of QDs for bioimaging and biosensing. This review will focus on the most recent progress of QDs for biomedical applications. Ample examples will be given in this review on newly developed synthetic methods of QDs, non-toxic QDs, QDs for biomolecule detection, cell and animal imaging, and disease therapy.
Co-reporter:Wei Wei;Xuewen He ; Nan Ma
Angewandte Chemie 2014 Volume 126( Issue 22) pp:5679-5683
Publication Date(Web):
DOI:10.1002/ange.201400428
Abstract
Quantum dots (QDs) hold great promise for the molecular imaging of cancer because of their superior optical properties. Although cell-surface biomarkers can be readily imaged with QDs, non-invasive live-cell imaging of critical intracellular cancer markers with QDs is a great challenge because of the difficulties in the automatic delivery of QD probes to the cytosol and the ambiguity of intracellular targeting signals. Herein, we report a new type of DNA-templated heterobivalent QD nanoprobes with the ability to target and image two spatially isolated cancer markers (nucleolin and mRNA) present on the cell surface and in the cell cytosol. Bypassing endolysosomal sequestration, this type of QD nanoprobes undergo macropinocytosis following the nucleolin targeting and then translocate to the cytosol for mRNA targeting. Fluorescence resonance energy transfer (FRET) based confocal microscopy enables unambiguous signal deconvolution of mRNA-targeted QD nanoprobes inside cancer cells.
Co-reporter:Xuewen He;Zhi Li;Muzi Chen ; Nan Ma
Angewandte Chemie 2014 Volume 126( Issue 52) pp:14675-14678
Publication Date(Web):
DOI:10.1002/ange.201408479
Abstract
Despite the widespread use of quantum dots (QDs) for biosensing and bioimaging, QD-based bio-interfaceable and reconfigurable molecular computing systems have not yet been realized. DNA-programmed dynamic assembly of multi-color QDs is presented for the construction of a new class of fluorescence resonance energy transfer (FRET)-based QD computing systems. A complete set of seven elementary logic gates (OR, AND, NOR, NAND, INH, XOR, XNOR) are realized using a series of binary and ternary QD complexes operated by strand displacement reactions. The integration of different logic gates into a half-adder circuit for molecular computation is also demonstrated. This strategy is quite versatile and straightforward for logical operations and would pave the way for QD-biocomputing-based intelligent molecular diagnostics.
Co-reporter:Jingwen Li, Xinming Li, Xiujuan Shi, Xuewen He, Wei Wei, Nan Ma, and Hong Chen
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 19) pp:9798
Publication Date(Web):September 9, 2013
DOI:10.1021/am4029735
We describe here a simple fluorometric assay for the highly sensitive detection of caspase-3 activities on the basis of the inner-filter effect of gold nanoparticles (AuNPs) on CdTe quantum dots (QDs). The method takes advantage of the high molar absorptivity of the plasmon band of gold nanoparticles as well as the large absorption band shift from 520 to 680 nm upon nanoparticle aggregation. When labeled with a peptide possessing the caspase-3 cleavage sequence (DEVD), the monodispersed Au-Ps (peptide-modified AuNPs) exhibited a tendency to aggregate when exposed to caspase-3, which induced the absorption band transition from 520 to 680 nm and turned on the fluorescence of the CdTe QDs for caspase-3 sensing. Under optimum conditions, a high sensitivity towards caspase-3 was achieved with a detection limit as low as 18 pM, which was much lower than the corresponding assays based on absorbance or other approaches. Overall, we demonstrated a facile and sensitive approach for caspase-3 detection, and we expected that this method could be potentially generalized to design more fluorescent assays for sensing other bioactive entities.Keywords: caspase-3; fluorescence; gold nanoparticle; inner-filter effect; quantum dot;
Co-reporter:Chi Chen, Xuewen He, Li Gao, and Nan Ma
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 3) pp:1149
Publication Date(Web):January 16, 2013
DOI:10.1021/am302933x
Facile aqueous synthesis of near-infrared Ag2Te quantum dots (QDs) and Ag2Te/ZnS core/shell QDs emitting in the second biological window is reported. The QD synthesis is based on a straightforward cation exchange process between CdTe QDs and Ag+ ions conducted in aqueous solution. The prepared Ag2Te QDs possess near-infrared emission ranging from 900 to 1300 nm and a quantum yield up to 2.1%. A ZnS shell was grown on the Ag2Te QD to further enhance the photoluminescence intensity with a quantum yield of 5.6%. These Ag2Te/ZnS core/shell QDs possess robust colloidal stability and photostability with minimum photoluminescence fluctuation upon incubation for 72 h in biological buffer or continuous laser excitation for 120 min. Also, These QDs possess small hydrodynamic size (∼7.6 nm) and are non-cytotoxic to human cells, which is ideal for optical bioimaging in the second biological window.Keywords: bioimaging; cation exchange; near-infrared; photoluminescence; quantum dot; silver chalcogenide;
Co-reporter:Dan Wu, Guofen Song, Zhi Li, Tao Zhang, Wei Wei, Muzi Chen, Xuewen He and Nan Ma
Chemical Science (2010-Present) 2015 - vol. 6(Issue 7) pp:NaN3844-3844
Publication Date(Web):2015/04/08
DOI:10.1039/C4SC03894K
Ideal theranostics should possess directly correlated imaging and therapy modalities that could be simultaneously activated in the disease site to generate high imaging contrast and therapeutic efficacy with minimal side effects. However, so far it still remains challenging to engineer all these characteristics into a single theranostic probe. Herein, we report a new type of photosensitizer (PS)-derived “two-dimensional” molecular beacon (TMB) that could be specifically activated within tumor cells to exhibit both high imaging contrast and therapeutic efficacy that outperforms conventional photosensitizers for cancer theranostics. The TMB is constructed by integrating a photosensitizer (chlorin e6 (Ce6)), a quantum dot (QD), and a dark quencher (BHQ3) into a hairpin DNA molecule to generate multiple synergistic FRET modes. The imaging modality and therapy modality, which are mediated by FRET between the QD and BHQ3 and FRET between the QD and Ce6 respectively, are interconnected within the TMB and could be simultaneously activated by tumor mRNA molecules. We show that highly effective cancer imaging and therapy could be achieved for cancer cell lines and xenografted tumor models. The reported TMB represents an unprecedented theranostic platform for intelligent cancer theranostics.
