CoChat
Sign Up
Cited by 168

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy

Zhan, Qi, Yi, Kaikai, Qi, Hongzhao, Li, Sidi, Li, Xueping, Wang, Qixue, Wang, Yunfei, Liu, Chaoyong, Qiu, Mingzhe, Yuan, Xubo, Zhao, Jin, Hou, Xin, Kang, Chunsheng·2020·Theranostics
DOI 10.7150/thno.45028PMC PMC7359100
Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.7150/thno.45028

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Figures

Scheme 1 Schematic representation of engineered blood exosomes for effective gene/chemo combined antitumor therapy. Taking full use of the structure and properties of the exosome membrane, such blood exosome-based co-delivery nanosystem tactfully integrates three moieties: co-loading of drugs and nucleic acids with high-payloads, tumor targeting and endosomal escaping. After intravenous injection, the engineered exosomes can accumulate at the tumor site with high-efficiency under an external magnetic field, following cellular uptake, the presence of endosomolytic peptide facilitates the effective release of therapeutic RNAs and chemotherapeutic drugs, resulting in a significantly improved gene/chemo combination antitumor effect.
Scheme 1 Schematic representation of engineered blood exosomes for effective gene/chemo combined antitumor therapy. Taking full use of the structure and properties of the exosome membrane, such blood exosome-based co-delivery nanosystem tactfully integrates three moieties: co-loading of drugs and nucleic acids with high-payloads, tumor targeting and endosomal escaping. After intravenous injection, the engineered exosomes can accumulate at the tumor site with high-efficiency under an external magnetic field, following cellular uptake, the presence of endosomolytic peptide facilitates the effective release of therapeutic RNAs and chemotherapeutic drugs, resulting in a significantly improved gene/chemo combination antitumor effect.CC BY · PubMed Central
Figure 1 Characterization of D-Exos/miR21i-L17E. (A, B) The particle size distribution and representative TEM images of SMNC-Exos and D-Exos/miR21i-L17E, respectively. (scale bar: 20 nm) (C) Western blots analysis of specific Tf receptors and exosome marker proteins (CD63, CD81 and CD9) of SMNC-Exos, D-Exos/miR21i and D-Exos/miR21i-L17E. (D) Detection of fluorescent signals in purified SMNC-Exos, D-Exos, D-Exos/miR21i and D-Exos/miR21i-L17E at different excitation/emission (Ex/Em) wavelength. The SMNC-Exos and chol-miR21i contained in each sample were labeled by FITC and Cy5, respectively. (E) UV-vis spectra of the SMNC-Exos, Dox, chol-miR21i-Cy5, L17E and D-Exos/miR21i-L17E. The inset shows the magnified UV-vis spectra from 600 to 700 nm. (F) Gel retention assay of D-Exos/miR21i prepared with D-Exos and varied concentrations of cholesterol-conjugated miR-21i or non-cholesterol-conjugated miR-21i. The Cy5-labeled miR-21i bands are displayed. (G) Schematic of the methods for confirming the localization of chol-miR21i on D-Exos/miR21i. Cy5-labeled miR-21 is complementary to chol-miR21i on D-Exos/miR21i. If miR-21i is completely display on the surface of exosomes, Cy5-miR21 will bind to D-Exos/miR21i, otherwise it will not. (H) Analysis for the binding of Cy5-miR21 to D-Exos/miR21i by gel electrophoresis. The Cy5-labeled miR-21 bands are displayed here. (I) Release profiles of Dox from D-Exos/miR21i-L17E in PBS (pH=7.4) and acetate buffer (pH=5.0) for 24 h. Data in (I) are presented as the mean ± standard deviation (SD) from three independent experiments (n=3).
Figure 1 Characterization of D-Exos/miR21i-L17E. (A, B) The particle size distribution and representative TEM images of SMNC-Exos and D-Exos/miR21i-L17E, respectively. (scale bar: 20 nm) (C) Western blots analysis of specific Tf receptors and exosome marker proteins (CD63, CD81 and CD9) of SMNC-Exos, D-Exos/miR21i and D-Exos/miR21i-L17E. (D) Detection of fluorescent signals in purified SMNC-Exos, D-Exos, D-Exos/miR21i and D-Exos/miR21i-L17E at different excitation/emission (Ex/Em) wavelength. The SMNC-Exos and chol-miR21i contained in each sample were labeled by FITC and Cy5, respectively. (E) UV-vis spectra of the SMNC-Exos, Dox, chol-miR21i-Cy5, L17E and D-Exos/miR21i-L17E. The inset shows the magnified UV-vis spectra from 600 to 700 nm. (F) Gel retention assay of D-Exos/miR21i prepared with D-Exos and varied concentrations of cholesterol-conjugated miR-21i or non-cholesterol-conjugated miR-21i. The Cy5-labeled miR-21i bands are displayed. (G) Schematic of the methods for confirming the localization of chol-miR21i on D-Exos/miR21i. Cy5-labeled miR-21 is complementary to chol-miR21i on D-Exos/miR21i. If miR-21i is completely display on the surface of exosomes, Cy5-miR21 will bind to D-Exos/miR21i, otherwise it will not. (H) Analysis for the binding of Cy5-miR21 to D-Exos/miR21i by gel electrophoresis. The Cy5-labeled miR-21 bands are displayed here. (I) Release profiles of Dox from D-Exos/miR21i-L17E in PBS (pH=7.4) and acetate buffer (pH=5.0) for 24 h. Data in (I) are presented as the mean ± standard deviation (SD) from three independent experiments (n=3).CC BY · PubMed Central
Figure 2 RNA transfection ability of SMNC-Exos modified with L17E peptide. (A) Fluorescence images of U87-GFP cells transfected with SMNC-Exos or SMNC-Exos-L17E carrying GFP siRNA (siGFP). The nucleus were stained with Hoechst 33342 (blue). The scale bar is 100 μm. (B) Western blot analysis of GFP protein expression. (C) Schematic representation of the luciferase reporter system (luc-hPEST-miR21). Luc: Firefly luciferase; hPEST: Protein degradation sequence (human-proline, glutamic acid, serine and threonine). Once exogenous miR-21i are transfected into cells via different nanocarriers and released into the cytoplasm, they block miR-21 associated with the 3'UTR of luciferase, which leads to decreased luciferase activity. (D) The bioluminescence of U87 cells after transfection of miR-21i into cells stably expressing luc-hPEST-miR21 by PEI, SMNC-Exos and SMNC-Exos-L17E. The results are expressed as RLU / mg protein. (E) Cell viability of U87 cells after treatment with SMNC-Exos containing different concentrations of L17E peptides for 24 h and 48 h. All data in (D) and (E) are presented as the mean ± SD from three independent experiments (n=3). The significant levels are shown as * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 2 RNA transfection ability of SMNC-Exos modified with L17E peptide. (A) Fluorescence images of U87-GFP cells transfected with SMNC-Exos or SMNC-Exos-L17E carrying GFP siRNA (siGFP). The nucleus were stained with Hoechst 33342 (blue). The scale bar is 100 μm. (B) Western blot analysis of GFP protein expression. (C) Schematic representation of the luciferase reporter system (luc-hPEST-miR21). Luc: Firefly luciferase; hPEST: Protein degradation sequence (human-proline, glutamic acid, serine and threonine). Once exogenous miR-21i are transfected into cells via different nanocarriers and released into the cytoplasm, they block miR-21 associated with the 3'UTR of luciferase, which leads to decreased luciferase activity. (D) The bioluminescence of U87 cells after transfection of miR-21i into cells stably expressing luc-hPEST-miR21 by PEI, SMNC-Exos and SMNC-Exos-L17E. The results are expressed as RLU / mg protein. (E) Cell viability of U87 cells after treatment with SMNC-Exos containing different concentrations of L17E peptides for 24 h and 48 h. All data in (D) and (E) are presented as the mean ± SD from three independent experiments (n=3). The significant levels are shown as * p < 0.05, ** p < 0.01, *** p < 0.001.CC BY · PubMed Central
Figure 3 Cellular uptake and intracellular distribution of D-Exos/miR21i-L17E. (A) Confocal images of U87 cells incubated with D-Exos/miR21i and D-Exos/miR21i-L17E for different times (1 h, 2 h, 4 h). The fluorescence spots of Dox (red) and chol-miR21i-Cy5 (purple) were observed. The nucleus and endo/lysosome were stained with DAPI (blue) and Lysotracker Green (green), respectively. (B) Co-localization ratio of the miR-21i signals (purple) in D-Exos/miR21i and D-Exos/miR21i-L17E to endosome signals (green) at different time points. (C) Flow cytometry profile of U87 cells incubated with free Dox and chol-miR21i, D-Exos, Exos/miR21i, D-Exos/miR21i and D-Exos/miR21i-L17E for 4 h. The y-axis represents cell counts and the x-axis represents the Dox and chol-miR21i-Cy5 fluorescence intensity, respectively. Data in (B) are presented as the mean ± SD (n>50) from three independent experiments (n=3). The significant levels are shown as ** p < 0.01, *** p < 0.001.
Figure 3 Cellular uptake and intracellular distribution of D-Exos/miR21i-L17E. (A) Confocal images of U87 cells incubated with D-Exos/miR21i and D-Exos/miR21i-L17E for different times (1 h, 2 h, 4 h). The fluorescence spots of Dox (red) and chol-miR21i-Cy5 (purple) were observed. The nucleus and endo/lysosome were stained with DAPI (blue) and Lysotracker Green (green), respectively. (B) Co-localization ratio of the miR-21i signals (purple) in D-Exos/miR21i and D-Exos/miR21i-L17E to endosome signals (green) at different time points. (C) Flow cytometry profile of U87 cells incubated with free Dox and chol-miR21i, D-Exos, Exos/miR21i, D-Exos/miR21i and D-Exos/miR21i-L17E for 4 h. The y-axis represents cell counts and the x-axis represents the Dox and chol-miR21i-Cy5 fluorescence intensity, respectively. Data in (B) are presented as the mean ± SD (n>50) from three independent experiments (n=3). The significant levels are shown as ** p < 0.01, *** p < 0.001.CC BY · PubMed Central
Figure 4 In vitro gene/chemo combination anticancer activity. (A, B) Relative expression levels of miR-21 in U87 (A) and MDA-MB-231 (B) cells after treatment with different samples. (C, D) Western blot analysis of AKT, BCL-2 and Caspase-3 protein expression in U87 (C) and MDA-MB-231 (D) cells after incubating with PBS, SMNC-Exos, D-Exos, D-Exos/miR21i, and D-Exos/miR21-L17E, respectively. Cell cytoskeleton protein (β-Actin) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are used as the loading control. (E) Cell apoptosis of U87 cells in each treatment group. Cell apoptosis ratios were assessed using flow cytometry. The data in (A, B) are presented as the mean ± SD from three independent experiments (n=3). The significance levels are shown as * p < 0.05, ** p < 0.01.
Figure 4 In vitro gene/chemo combination anticancer activity. (A, B) Relative expression levels of miR-21 in U87 (A) and MDA-MB-231 (B) cells after treatment with different samples. (C, D) Western blot analysis of AKT, BCL-2 and Caspase-3 protein expression in U87 (C) and MDA-MB-231 (D) cells after incubating with PBS, SMNC-Exos, D-Exos, D-Exos/miR21i, and D-Exos/miR21-L17E, respectively. Cell cytoskeleton protein (β-Actin) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are used as the loading control. (E) Cell apoptosis of U87 cells in each treatment group. Cell apoptosis ratios were assessed using flow cytometry. The data in (A, B) are presented as the mean ± SD from three independent experiments (n=3). The significance levels are shown as * p < 0.05, ** p < 0.01.CC BY · PubMed Central
Figure 5 Tumor targeting efficiency of engineered exosomes in tumor-bearing mice in vivo. (A) In vivo NIRF imaging of U87 tumor-bearing nude mice after intravenous injection of Cy5.5-labeled D-Exos/miR21i-L17E with/without an external MF at 1 h, 4 h and 24 h post-injection. (B) Quantitative analysis of the tumor accumulation of the D-Exos/miR21i-L17E based on the fluorescence intensity from the in vivo images. (C) The accumulation of Dox and Cy5-miR21i in the tumor section, where red represents Dox, green represents miR21i and cell nucleus was stained by DAPI. The scale bar is 100 μm. Data in (B) are presented as the mean ± SD (n=5).
Figure 5 Tumor targeting efficiency of engineered exosomes in tumor-bearing mice in vivo. (A) In vivo NIRF imaging of U87 tumor-bearing nude mice after intravenous injection of Cy5.5-labeled D-Exos/miR21i-L17E with/without an external MF at 1 h, 4 h and 24 h post-injection. (B) Quantitative analysis of the tumor accumulation of the D-Exos/miR21i-L17E based on the fluorescence intensity from the in vivo images. (C) The accumulation of Dox and Cy5-miR21i in the tumor section, where red represents Dox, green represents miR21i and cell nucleus was stained by DAPI. The scale bar is 100 μm. Data in (B) are presented as the mean ± SD (n=5).CC BY · PubMed Central
Figure 6 Gene/chemo combination antitumor efficacy of D-Exos/miR21i-L17E in vivo. (A) Tumor growth curves of U87 subcutaneous tumor in nude mice injected with PBS, SMNC-Exos, Dox, D-Exos, Exos/miR21i, D-Exos/miR21i and D-Exos/miR21i-L17E. Every mouse was applied with a MF of 1T. Tumor volume was examined every 3 days for 18 consecutive days. (B) Ex vivo photograph of the tumors from the treated mice at 18 days' post-injection. (C) Comparison of the weight of collected tumor tissues from the mice treated with different formulations. (D) Changes in body weight of the mice with different treatment. (E) RNA in situ hybridization presenting the expression of miR-21 in the tumor tissue from the mice of each treatment group. Nucleus is stained blue, and miR-21 is stained brown. The scale bar is 50 μm. (F) Immunohistochemistry analyses of the expression of p-Akt, Bcl-2 and Caspase-3 in each treatment group. Nuclei are stained blue, and the proteins are stained brown. The scale bar is 200 μm. (G) TUNEL analysis of the tumor tissues from the mice in each treatment group. Normal cell nuclei are stained blue, and apoptotic cell nuclei are stained red. The scale bar is 100 μm. Data in (A) are presented as the mean ± SEM, and data in (C, D) are presented as the mean ± SD (n=5). The significance levels are shown as * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 6 Gene/chemo combination antitumor efficacy of D-Exos/miR21i-L17E in vivo. (A) Tumor growth curves of U87 subcutaneous tumor in nude mice injected with PBS, SMNC-Exos, Dox, D-Exos, Exos/miR21i, D-Exos/miR21i and D-Exos/miR21i-L17E. Every mouse was applied with a MF of 1T. Tumor volume was examined every 3 days for 18 consecutive days. (B) Ex vivo photograph of the tumors from the treated mice at 18 days' post-injection. (C) Comparison of the weight of collected tumor tissues from the mice treated with different formulations. (D) Changes in body weight of the mice with different treatment. (E) RNA in situ hybridization presenting the expression of miR-21 in the tumor tissue from the mice of each treatment group. Nucleus is stained blue, and miR-21 is stained brown. The scale bar is 50 μm. (F) Immunohistochemistry analyses of the expression of p-Akt, Bcl-2 and Caspase-3 in each treatment group. Nuclei are stained blue, and the proteins are stained brown. The scale bar is 200 μm. (G) TUNEL analysis of the tumor tissues from the mice in each treatment group. Normal cell nuclei are stained blue, and apoptotic cell nuclei are stained red. The scale bar is 100 μm. Data in (A) are presented as the mean ± SEM, and data in (C, D) are presented as the mean ± SD (n=5). The significance levels are shown as * p < 0.05, ** p < 0.01, *** p < 0.001.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 5 references

Research works printed but not linked: 49

  1. [1]Shi J Kantoff PW Wooster R Farokhzad OC Cancer nanomedicine: progress, challenges and opportunities Nat Rev Cancer 2017 17 20 37 27834398 PMC5575742
  2. [2]Xu X Ho W Zhang X Bertrand N Farokhzad O Cancer nanomedicine: from targeted delivery to combination therapy Trends Mol Med 2015 21 223 32 25656384 PMC4385479
  3. [3]Hu Q Sun W Wang C Gu Z Recent advances of cocktail chemotherapy by combination drug delivery systems Adv Drug Deliv Rev 2016 98 19 34 26546751 PMC4998845
  4. [4]Sun Q Zhou Z Qiu N Shen Y Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization Adv Mater 2017 29 1606628 28234430
  5. [5]van der Meel R Sulheim E Shi Y Kiessling F Mulder WJM Lammers T Smart cancer nanomedicine Nat Nanotechnol 2019 14 1007 17 31695150 PMC7227032
  6. [6]Huang W Chen L Kang L Jin M Sun P Xin X Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs Adv Drug Deliv Rev 2017 115 82 97 28624478
  7. [7]Ding Y Su S Zhang R Shao L Zhang Y Wang B Precision combination therapy for triple negative breast cancer via biomimetic polydopamine polymer core-shell nanostructures Biomaterials 2017 113 243 52 27829203
  8. [8]Li C Yang XQ Zhang MZ Song YY Cheng K An J In vivo Imaging-Guided Nanoplatform for Tumor Targeting Delivery and Combined Chemo-, Gene- and Photothermal Therapy Theranostics 2018 8 5662 75 30555572 PMC6276300
  9. [9]Prencipe G Tabakman SM Welsher K Liu Z Goodwin AP Zhang L PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation J Am Chem Soc 2009 131 4783 7 19173646 PMC2827329
  10. [11]Allen TM Ligand-targeted therapeutics in anticancer therapy Nat Rev Cancer 2002 2 750 63 12360278
  11. [12]Vaughan HJ Green JJ Tzeng SY Cancer-Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery Adv Mater. 2019: e1901081 PMC6923623 31222852
  12. [13]Samal SK Dash M Van Vlierberghe S Kaplan DL Chiellini E van Blitterswijk C Cationic polymers and their therapeutic potential Chem Soc Rev 2012 41 7147 94 22885409
  13. [14]Yu H Guo C Feng B Liu J Chen X Wang D Triple-Layered pH-Responsive Micelleplexes Loaded with siRNA and Cisplatin Prodrug for NF-Kappa B Targeted Treatment of Metastatic Breast Cancer Theranostics 2016 6 14 27 26722370 PMC4679351
  14. [15]Mura S Nicolas J Couvreur P Stimuli-responsive nanocarriers for drug delivery Nat Mater 2013 12 991 1003 24150417
  15. [17]Wang S Huang P Chen X Stimuli-Responsive Programmed Specific Targeting in Nanomedicine ACS Nano 2016 10 2991 4 26881288 PMC5223089
  16. [18]El-Sawy HS Al-Abd AM Ahmed TA El-Say KM Torchilin VP Stimuli-Responsive Nano-Architecture Drug-Delivery Systems to Solid Tumor Micromilieu: Past, Present, and Future Perspectives ACS Nano 2018 12 10636 64 30335963
  17. [19]Wang C Li Z Cao D Zhao YL Gaines JW Bozdemir OA Stimulated release of size-selected cargos in succession from mesoporous silica nanoparticles Angew Chem Int Ed Engl 2012 51 5460 5 22505218
  18. [20]Sun Q Sun X Ma X Zhou Z Jin E Zhang B Integration of nanoassembly functions for an effective delivery cascade for cancer drugs Adv Mater 2014 26 7615 21 25328159
  19. [21]Chen B Dai W He B Zhang H Wang X Wang Y Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment Theranostics 2017 7 538 58 28255348 PMC5327631
  20. [22]Saw PE Yao H Lin C Tao W Farokhzad OC Xu X Stimuli-Responsive Polymer-Prodrug Hybrid Nanoplatform for Multistage siRNA Delivery and Combination Cancer Therapy Nano Lett 2019 19 5967 74 31381852
  21. [23]Mathieu M Martin-Jaular L Lavieu G Théry C Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication Nat Cell Biol 2019 21 9 17 30602770
  22. [24]Syn NL Wang L Chow EK Lim CT Goh BC Exosomes in Cancer Nanomedicine and Immunotherapy: Prospects and Challenges Trends Biotechnol 2017 35 665 76 28365132
  23. [25]Yang B Chen Y Shi J Exosome Biochemistry and Advanced Nanotechnology for Next-Generation Theranostic Platforms Adv Mater 2019 31 e1802896 30126052
  24. [26]Lener T Gimona M Aigner L Borger V Buzas E Camussi G Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper J Extracell Vesicles 2015 4 30087 26725829 PMC4698466
  25. [28]Pegtel DM Gould SJ Exosomes Annu Rev Biochem 2019 88 487 514 31220978
  26. [29]S ELA Mäger I Breakefield XO Wood MJ Extracellular vesicles: biology and emerging therapeutic opportunities Nat Rev Drug Discov 2013 12 347 57 23584393
  27. [30]Valadi H Ekström K Bossios A Sjöstrand M Lee JJ Lötvall JO Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells Nat Cell Biol 2007 9 654 9 17486113
  28. [31]Alvarez-Erviti L Seow Y Yin H Betts C Lakhal S Wood MJ Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes Nat Biotechnol 2011 29 341 5 21423189
  29. [33]Yong T Zhang X Bie N Zhang H Zhang X Li F Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy Nat Commun 2019 10 3838 31444335 PMC6707218
  30. [34]Cheng Q Shi X Han M Smbatyan G Lenz HJ Zhang Y Reprogramming Exosomes as Nanoscale Controllers of Cellular Immunity J Am Chem Soc 2018 140 16413 7 30452238 PMC6469991
  31. [35]Sancho-Albero M Rubio-Ruiz B Perez-Lopez AM Sebastian V Martin-Duque P Arruebo M Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis Nat Catal 2019 2 864 72 31620674 PMC6795537
  32. [37]Gong C Tian J Wang Z Gao Y Wu X Ding X Functional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy J Nanobiotechnology 2019 17 93 31481080 PMC6721253
  33. [38]Blanc L De Gassart A Géminard C Bette-Bobillo P Vidal M Exosome release by reticulocytes-an integral part of the red blood cell differentiation system Blood Cells Mol Dis 2005 35 21 6 15946868
  34. [39]Qi H Liu C Long L Ren Y Zhang S Chang X Blood Exosomes Endowed with Magnetic and Targeting Properties for Cancer Therapy ACS Nano 2016 10 3323 33 26938862
  35. [40]Akishiba M Takeuchi T Kawaguchi Y Sakamoto K Yu HH Nakase I Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide Nat Chem 2017 9 751 61 28754944
  36. [41]Pi F Binzel DW Lee TJ Li Z Sun M Rychahou P Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression Nat Nanotechnol 2018 13 82 9 29230043 PMC5762263
  37. [42]Wan Y Wang L Zhu C Zheng Q Wang G Tong J Aptamer-Conjugated Extracellular Nanovesicles for Targeted Drug Delivery Cancer Res 2018 78 798 808 29217761 PMC5811376
  38. [43]Yerneni SS Lathwal S Shrestha P Shirwan H Matyjaszewski K Weiss L Rapid On-Demand Extracellular Vesicle Augmentation with Versatile Oligonucleotide Tethers ACS Nano 2019 13 10555 65 31436946 PMC6800810
  39. [44]Armstrong JP Holme MN Stevens MM Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics ACS Nano 2017 11 69 83 28068069 PMC5604727
  40. [45]Kooijmans SAA Stremersch S Braeckmans K de Smedt SC Hendrix A Wood MJA Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles J Control Release 2013 172 229 38 23994516
  41. [47]Rogers S Wells R Rechsteiner M Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis Science 1986 234 364 8 2876518
  42. [48]Selby LI Cortez-Jugo CM Such GK Johnston APR Nanoescapology: progress toward understanding the endosomal escape of polymeric nanoparticles Wiley Interdiscip Rev Nanomed Nanobiotechnol 2017 9 e1452 28160452
  43. [49]Lewinski N Colvin V Drezek R Cytotoxicity of nanoparticles Small 2008 4 26 49 18165959
  44. [50]Deng H Lin L Wang S Yu G Zhou Z Liu Y X-ray-Controlled Bilayer Permeability of Bionic Nanocapsules Stabilized by Nucleobase Pairing Interactions for Pulsatile Drug Delivery Adv Mater 2019 31 e1903443 31379091
  45. [51]Zhu S Wu H Wu F Nie D Sheng S Mo YY MicroRNA-21 targets tumor suppressor genes in invasion and metastasis Cell Res 2008 18 350 9 18270520
  46. [52]Hong L Han Y Zhang Y Zhang H Zhao Q Wu K MicroRNA-21: a therapeutic target for reversing drug resistance in cancer Expert Opin Ther Targets 2013 17 1073 80 23865553
  47. [53]Zhou X Ren Y Moore L Mei M You Y Xu P Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status Lab Invest 2010 90 144 55 20048743
  48. [54]Han L Liu C Qi H Zhou J Wen J Wu D Systemic Delivery of Monoclonal Antibodies to the Central Nervous System for Brain Tumor Therapy Adv Mater 2019 31 e1805697 30773720
  49. [55]Usman WM Pham TC Kwok YY Vu LT Ma V Peng B Efficient RNA drug delivery using red blood cell extracellular vesicles Nat Commun 2018 9 2359 29907766 PMC6004015

Cited by

Sorted by citations

Metadata

Authors
Zhan, Q., Yi, K., Qi, H., Li, S., Li, X., Wang, Q., Wang, Y., Liu, C., Qiu, M., Yuan, X., Zhao, J., Hou, X., & Kang, C.
Venue
Theranostics
Publisher
Ivyspring International Publisher
Published
2020
Volume
10
Issue
17
Pages
7889-7905
ISSN
1838-7640
DOI
10.7150/thno.45028
PMC
PMC7359100
Cited by
168
References
5
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review