Co-reporter:Penghui Zhang, Chen Wang, Jingjing Zhao, Anqi Xiao, Qi Shen, Linting Li, Jianxin Li, Junfeng Zhang, Qianhao Min, Jiangning Chen, Hong-Yuan Chen, and Jun-Jie Zhu
ACS Nano 2016 Volume 10(Issue 3) pp:3637
Publication Date(Web):February 23, 2016
DOI:10.1021/acsnano.5b08145
In chemotherapy, it is a great challenge to recruit endogenous stimuli instead of external intervention for targeted delivery and controlled release; microRNAs are the most promising candidates due to their vital role during tumorigenesis and significant expression difference. Herein, to amplify the low abundant microRNAs in live cells, we designed a stimuli-responsive DNA Y-motif for codelivery of siRNA and Dox, in which the cargo release was achieved via enzyme-free cascade amplification with endogenous microRNA as trigger and ATP (or H+) as fuel through toehold-mediated strand displacement. Furthermore, to realize controlled release in tumor cells, smart nanocarriers were constructed with stimuli-responsive Y-motifs, gold nanorods, and temperature-sensitive polymers, whose surfaces could be reversibly switched between PEG and RGD states via photothermal conversion. The PEG corona kept the nanocarriers stealth during blood circulation to protect the Y-motifs against nuclease digestion and enhance passive accumulation, whereas the exposed RGD shell under near-infrared (NIR) irradiation at tumor sites facilitated the specific receptor-mediated endocytosis by tumor cells. Through modulating NIR laser, microRNA, or ATP expressions, the therapy efficacies to five different cell lines were finely controlled, presenting NIR-guided accumulation, massive release, efficient gene silence, and severe apoptosis in HeLa cells; in vivo study showed that a low dosage of nanocarriers synergistically inhibited the tumor growth by silencing gene expression and inducing cell apoptosis under mild NIR irradiation, though they only brought minimum damage to normal organs. The combination of nanomaterials, polymers, and DNA nanomachines provided a promising tool for designing smart nanodevices for disease therapy.Keywords: aptamer; DNA nanomachine; drug delivery; microRNA; smart nanocarriers
Co-reporter:Zixuan Chen; Jingjing Li; Xueqin Chen; Juntao Cao; Jianrong Zhang; Qianhao Min;Jun-Jie Zhu
Journal of the American Chemical Society 2015 Volume 137(Issue 5) pp:1903-1908
Publication Date(Web):January 21, 2015
DOI:10.1021/ja5112628
This article describes a multimodified core–shell gold@silver nanoprobe for real-time monitoring the entire autophagy process at single-cell level. Autophagy is vital for understanding the mechanisms of human pathologies, developing novel drugs, and exploring approaches for autophagy controlling. A major challenge for autophagy study lies in real-time monitoring. One solution might come from real-time detection of in situ superoxide radicals (O2•–), because it is the main regulator of autophagy. In this work, our proposed nanoprobes were etched by O2•– and gave a notable wavelength change in the plasmon resonance scattering spectra. Both the experimental and simulated results suggested the wavelength change rate correlated well with O2•– level. This response enabled its application in real-time in situ quantification of O2•– during autophagy course. More importantly, with the introduction of “relay probe” operation, two types of O2•–-regulating autophagy processes were successfully traced from the beginning to the end, and the possible mechanism was also proposed.
Co-reporter:Xueqin Chen, Siyuan Li, Xiaoxia Zhang, Qianhao Min and Jun-Jie Zhu
Nanoscale 2015 vol. 7(Issue 13) pp:5815-5825
Publication Date(Web):29 Jan 2015
DOI:10.1039/C4NR07041K
Qualitative and quantitative characterization of phosphopeptides by means of mass spectrometry (MS) is the main goal of MS-based phosphoproteomics, but suffers from their low abundance in the large haystack of various biological molecules. Herein, we introduce two-dimensional (2D) metal oxides to tackle this biological separation issue. A nanocomposite composed of titanoniobate nanosheets embedded with Fe3O4 nanocrystals (Fe3O4–TiNbNS) is constructed via a facile cation-exchange approach, and adopted for the capture and isotope labeling of phosphopeptides. In this nanoarchitecture, the 2D titanoniobate nanosheets offer enlarged surface area and a spacious microenvironment for capturing phosphopeptides, while the Fe3O4 nanocrystals not only incorporate a magnetic response into the composite but, more importantly, also disrupt the restacking process between the titanoniobate nanosheets and thus preserve a greater specific surface for binding phosphopeptides. Owing to the extended active surface, abundant Lewis acid sites and excellent magnetic controllability, Fe3O4–TiNbNS demonstrates superior sensitivity, selectivity and capacity over homogeneous bulk metal oxides, layered oxides, and even restacked nanosheets in phosphopeptide enrichment, and further allows in situ isotope labeling to quantify aberrantly-regulated phosphopeptides from sera of leukemia patients. This composite nanosheet greatly contributes to the MS analysis of phosphopeptides and gives inspiration in the pursuit of 2D structured materials for separation of other biological molecules of interests.
Co-reporter:Penghui Zhang, Zhimei He, Chen Wang, Jiangning Chen, Jingjing Zhao, Xuena Zhu, Chen-Zhong Li, Qianhao Min, and Jun-Jie Zhu
ACS Nano 2015 Volume 9(Issue 1) pp:789
Publication Date(Web):December 19, 2014
DOI:10.1021/nn506309d
MicroRNAs (miRNAs), as key regulators in gene expression networks, have participated in many biological processes, including cancer initiation, progression, and metastasis, indicative of potential diagnostic biomarkers and therapeutic targets. To tackle the low abundance of miRNAs in a single cell, we have developed programmable nanodevices with MNAzymes to realize stringent recognition and in situ amplification of intracellular miRNAs for multiplexed detection and controlled drug release. As a proof of concept, miR-21 and miR-145, respectively up- and down-expressed in most tumor tissues, were selected as endogenous cancer indicators and therapy triggers to test the efficacy of the photothermal nanodevices. The sequence programmability and specificity of MNAzyme motifs enabled the fluorescent turn-on probes not only to sensitively profile the distributions of miR-21/miR-145 in cell lysates of HeLa, HL-60, and NIH 3T3 (9632/0, 14147/0, 2047/421 copies per cell, respectively) but also to visualize trace amounts of miRNAs in a single cell, allowing logic operation for graded cancer risk assessment and dynamic monitoring of therapy response by confocal microscopy and flow cytometry. Furthermore, through general molecular design, the MNAzyme motifs could serve as three-dimensional gatekeepers to lock the doxorubicin inside the nanocarriers. The drug nanocarriers were exclusively internalized into the target tumor cells via aptamer-guided recognition and reopened by the endogenous miRNAs, where the drug release rates could be spatial-temporally controlled by the modulation of miRNA expression. Integrated with miRNA profiling techniques, the designed nanodevices can provide general strategy for disease diagnosis, prognosis, and combination treatment with chemotherapy and gene therapy.Keywords: DNAzyme; drug delivery; intracellular imaging; logic operation; microRNAs;
Co-reporter:Penghui Zhang;Fangfang Cheng;Ri Zhou;Dr. Juntao Cao;Dr. Jingjing Li;Dr. Clemens Burda;Dr. Qianhao Min;Dr. Jun-Jie Zhu
Angewandte Chemie International Edition 2014 Volume 53( Issue 9) pp:2371-2375
Publication Date(Web):
DOI:10.1002/anie.201308920
Abstract
The design of an ideal drug delivery system with targeted recognition and zero premature release, especially controlled and specific release that is triggered by an exclusive endogenous stimulus, is a great challenge. A traceable and aptamer-targeted drug nanocarrier has now been developed; the nanocarrier was obtained by capping mesoporous silica-coated quantum dots with a programmable DNA hybrid, and the drug release was controlled by microRNA. Once the nanocarriers had been delivered into HeLa cells by aptamer-mediated recognition and endocytosis, the overexpressed endogenous miR-21 served as an exclusive key to unlock the nanocarriers by competitive hybridization with the DNA hybrid, which led to a sustained lethality of the HeLa cells. If microRNA that is exclusively expressed in specific pathological cell was screened, a combination of chemotherapy and gene therapy should pave the way for a targeted and personalized treatment of human diseases.
Co-reporter:Penghui Zhang;Fangfang Cheng;Ri Zhou;Dr. Juntao Cao;Dr. Jingjing Li;Dr. Clemens Burda;Dr. Qianhao Min;Dr. Jun-Jie Zhu
Angewandte Chemie 2014 Volume 126( Issue 9) pp:2403-2407
Publication Date(Web):
DOI:10.1002/ange.201308920
Abstract
The design of an ideal drug delivery system with targeted recognition and zero premature release, especially controlled and specific release that is triggered by an exclusive endogenous stimulus, is a great challenge. A traceable and aptamer-targeted drug nanocarrier has now been developed; the nanocarrier was obtained by capping mesoporous silica-coated quantum dots with a programmable DNA hybrid, and the drug release was controlled by microRNA. Once the nanocarriers had been delivered into HeLa cells by aptamer-mediated recognition and endocytosis, the overexpressed endogenous miR-21 served as an exclusive key to unlock the nanocarriers by competitive hybridization with the DNA hybrid, which led to a sustained lethality of the HeLa cells. If microRNA that is exclusively expressed in specific pathological cell was screened, a combination of chemotherapy and gene therapy should pave the way for a targeted and personalized treatment of human diseases.
