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RISS 인기검색어
- 검색키워드
- 저자 : Xiuru Ji (검색결과 2 건)
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MMP-2-responsive fluorescent nanoprobes for enhanced selectivity of tumor cell uptake and imaging
Sun, Lu,Xie, Shuping,Ji, Xiuru,Zhang, Jingming,Wang, Dongmei,Lee, Seung Jin,Lee, Hyukjin,He, Huining,Yang, Victor C. The Royal Society of Chemistry 2018 Biomaterials Science Vol.6 No.10
<P>It is difficult to develop highly selective substrate-based fluorescent nanoprobes for specific matrix metalloproteinases (MMPs) due to overlapping substrate specificities among the family of MMP enzymes. To resolve this issue, we have developed novel fluorescent nanoprobes that are highly selective for soluble MMP-2. Herein, MMP-2-responsive nanoprobes were prepared by immobilizing fluorescent fusion proteins on nickel ferrite nanoparticles <I>via</I> the His-tag nickel chelation mechanism. The fusion protein consisted of a fluorescent mCherry protein with a cell penetrating peptide (CPP) moiety. An MMP-2 cleavage site was also introduced within the fusion protein, which was directly linked to the nickel ferrite nanoparticles. The selectivity of nanoprobes was modulated by hiding the cleavage site of MMP-2 substrates deeply inside the system, which could result in strong steric hindrance between the nanoprobes and MMPs, especially for membrane-tethered MMPs such as MMP-14. A cell-based assay demonstrated that the nanoprobes could only be activated by tumor cells secreting soluble MMP-2, but not membrane-tethered MMP-14. To further evaluate the contribution of the steric hindrance effect on the nanoprobes, a truncated recombinant MMP-14 was employed to confer their cleavage activity as compared to native membrane-tethered MMP-14. Furthermore, a designed probe with a diminished steric hindrance effect was proved to be activated by membrane-tethered type MMP-14. The results indicated that the design of fluorescent nanoprobes employing the steric hindrance effect can greatly enhance the selectivity of MMP-responsive nanoprobes realizing the specific detection of soluble MMP-2 in a tumor microenvironment. We believe that highly selective MMP-2-responsive fluorescent nanoprobes have broad impacts on biomedical applications including molecular imaging and labeling for tumor detection.</P>
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A self-assembly and stimuli-responsive fusion gelonin delivery system for tumor treatment
Quan Liu,Lu Zhang,Xiuru Ji,Meong Cheol Shin,Shuping Xie,Baoyan Pan,Fei Yu,Jingwen Zhao,Victor C. Yang 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.89 No.-
Ribosome-inactivating proteins (RIPs) are potent protein toxins for cancer therapy, and they have strongability to inhibit protein synthesis and induce cell death via inactivation of ribosomes in eukaryotic cells. However, the delivery of RIPs has been a challenging task due to their large molecular weight and lack oftargeting property. Low molecular weight protamine (LMWP), a transmembrane peptide, has beenproved to effectively promote transmembrane transportation, whereas the enzyme-activatable systemcan enhance the specificity by enhancing the tumor drug concentration through enzymatic reaction. Weherein constructed a self-assembly and stimuli-responsive fusion gelonin delivery system. Gelonin, atypical RIP protein, was assembled with nickel ferrite nanoparticles by self-assembling between hexa-histidine tag (His-tagged) and nickel ions. Both in vitro and in vivo results indicated that the magneticnanoparticle carriers and the applied linkers did not damage the pharmaceutical effect of gelonin, andthe whole drug delivery system showed good biocompatibility, sensitive selectivity, and significantlyenhanced cytotoxic activity. This in turn presented theranostic nanoparticles as efficient delivery vehiclefor clinical use.
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