Controllable Assembly and Properties of Brain Targeting Peptides with Tetrahedral Framework Nucleic Acids

doi:10.19894/j.issn.1000-0518.220038

Chinese Journal of Applied Chemistry ›› 2022, Vol. 39 ›› Issue (10): 1501-1509.DOI: 10.19894/j.issn.1000-0518.220038

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Controllable Assembly and Properties of Brain Targeting Peptides with Tetrahedral Framework Nucleic Acids

Mei-Ling YAN¹^,⁴, Hong-Zhen PENG¹^,², Ting-Ting ZUO¹^,⁴, Tian TIAN³(), Ying ZHU¹^,², Yan-Hong SUN¹^,²()

^1.CAS Key Laboratory of Interfacial Physics and Technology，Shanghai Institute of Applied Physics，Chinese Academy of Sciences，Shanghai 201800，China
^2.The Interdiciplinary Research Center，Shanghai Advanced Research Institute，Chinese Academy of Sciences，Shanghai 201210，China
^3.Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China
^4.University of Chinese Academy of Sciences，Beijing 100049，China

Received:2022-02-17 Accepted:2022-06-06 Published:2022-10-01 Online:2022-10-05
Contact: Tian TIAN,Yan-Hong SUN
About author:sunyanhong@sinap.ac.cn
tiantian@shutcm.edu.cn；
Supported by:
the National Science Foundation of China(22022410);Shanghai Municipal Science and Technology Commission(19JC1410300)

Abstract

Abstract:

In this study， the armed tetrahedral DNA nanostructures （TDN） are designed to bind single or three complementary strands of armed chain （1-ANG-TDN， 3-ANG-TDN） which is modified with angiopep-2 or other brain targeting peptides （TAT， TGN）. We compare the cell viability and cellular uptake of 1-ANG-TDN or 3-ANG-TDN in brain capillary endothelial （bEnd.3） cells and Uppsala 87 malignant glioma （U87） cells. In addition， the cell viability and cellular uptake of ANG-TDN， TAT-TDN and TGN-TDN in bEnd.3 cells are investigated respectively. The results show that these probes are not cytotoxic to bEnd.3 cells and U87 cells at concentrationsbelow 100 nmol/L. After being incubated with bEnd.3cells for 0.5 h， the cellular uptake of 3-ANG-TDN is higher than that of 1-ANG-TDN （P<0.01）. After being incubated with U87 cells for 1h， the cellular uptake of 3-ANG-TDN is higher than that of 1-ANG-TDN （P<0.01）. After 2 h， there is no obvious difference in cellular uptake between 1-ANG-TDN and 3-ANG-TDN. ANG-TDN， TAT-TDN and TGN-TDN are up-taken by bEnd.3 cells much more than TDN （P<0.01）. However， there isno statistical difference among ANG-TDN， TAT-TDN and TGN-TDN （P>0.05）. These results indicate that the targeting of ANG-TDN probe can be improved by increasing the number of peptides or prolonging the co-incubation time. This discovery providesareference for the multifunctional modification of tetrahedral framework nucleic acid. When a single peptidelinked with TDN achieves the brain targeting， other sites of TDN can be modified by other functional groups to expand the structure and function. Tetrahedral framework nucleic acids can be used not only as an assembly platform for ANG peptides， but also for the assembly of other brain-targeting peptides （TAT and TGN） to design brain-targeting probes.

Key words: Tetrahedral framework nucleic acid, Brain-targeting probes, Controllable assembly, Targeted uptake

CLC Number:

O655

Mei-Ling YAN, Hong-Zhen PENG, Ting-Ting ZUO, Tian TIAN, Ying ZHU, Yan-Hong SUN. Controllable Assembly and Properties of Brain Targeting Peptides with Tetrahedral Framework Nucleic Acids[J]. Chinese Journal of Applied Chemistry, 2022, 39(10): 1501-1509.

Figures/Tables 4

Fig.1 Structural characterization of tetrahedral DNA nanostructures modified with different numbers of Angiopep-2-peptides（ANG）A. Schematic diagram of the probe structures； B. PAGE analysis of tetrahedral DNA nanostructures modified with different numbers of Angiopep-2 peptides （line 1： DNA marker， line 2： TDN， line 3： armed-TDN， line 4： 1-ANG-TDN，line 5： 3-ANG-TDN）； C. AFM images of TDN； D. AFM images of ANG-TDN

Fig.2 Cytotoxicity of tetrahedral DNA （TDN） modified with different numbers of ANG peptides （ANG-TDN）A-C. Cell viability of bEnd.3 cellsafter incubating with TDN， 1-ANG-TDN and 3-ANG-TDN cells for 24 h； D-F. Cell viability of U 87 cells after incubating with TDN， 1-ANG-TDN and 3-ANG-TDN for 24 h

Fig.3 Cell uptake of TDN， 1-ANG-TDN and 3-ANG-TDN in bEend.3 and U87 cellsA-C. Confocal images（4 h）， flow analysis（0.5，1，2，4 h） and statistical analysis （0.5， 1， 2 h） of cellular uptake of TDN， 1-ANG-TDN and 3-ANG-TDN in bEend.3 cells. D-F. Confocal images， flow analysis and statistical analysis of cellular uptake of TDN， 1-ANG-TDN and 3-ANG-TDN in U87 cells. In （B），（C），（E），（F）， Mean Fluorescence Intensity， MFI.（* represents P<0.05，** represents P<0.01，ns represents P>0.05）

Fig.4 Structural characterization， cytotoxicity and cellular uptake of different brain targetedframe nucleic acid probes（TGN-TDN， ANG-TDN and TAT-TDN）A. PAGE gel electrophoresis analysis of TGN-TDN， ANG-TDN and TAT-TDN （line 1： DNA marker， line 2： TDN， line 3：Armed-TDN， line 4： TGN-TDN， line 5： ANG-TDN， line 6： TAT-TDN）. B-C. Cytotoxicity of TGN-TDN， ANG-TDN and TAT-TDN. D. Cellular uptake of TGN-TDN， ANG-TDN and TAT-TDN in bEnd.3 cells. E. Statistical analysis of cellular uptake of TDN， TGN-TDN，ANG-TDN and TAT-TDN in bEnd.3 cells（* represents P<0.05，** represents P<0.01，ns represents P>0.05）

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Controllable Assembly and Properties of Brain Targeting Peptides with Tetrahedral Framework Nucleic Acids

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