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Polypeptide, lipoprotein-like nano particle and application thereof

A nanoparticle and lipoprotein technology, applied in apolipoproteins, fusion polypeptides, animal/human proteins, etc., can solve the application limitations of high-density lipoprotein nanoparticles, high cost of ApoA-I protein synthesis, difficult functional modification, etc. problem, to achieve the effect of multi-function, high stability and easy functionalization

Active Publication Date: 2017-06-13
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the synthesis cost of ApoA-I protein is high, and it is difficult to carry out functional modification, which limits the application of high-density lipoprotein nanoparticles.

Method used

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  • Polypeptide, lipoprotein-like nano particle and application thereof
  • Polypeptide, lipoprotein-like nano particle and application thereof
  • Polypeptide, lipoprotein-like nano particle and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0107] In the lipoprotein-like nanoparticles based on the helix-loop-helix structure polypeptide of this embodiment, the helix-loop-helix structure polypeptide (ALA polypeptide) is composed of an α-helix polypeptide, a cyclization sequence and an α-helix polypeptide in the form of a covalent bond concatenated. Wherein the amino acid sequence of the α-helical polypeptide is: GSFLSALEEWTKKLN, but it is not limited to this sequence. The cyclized polypeptide sequences are respectively SGS, SGSGS, and SGSGSGS, but are not limited to this sequence, and may also be other sequences with specific functions.

[0108] One of the AL 5 The synthesis process of A polypeptide is as follows: adopt solid-phase synthesis method (refer to literature 1 and literature 2), use Fmoc amino acid, dichlorotrityl resin as carrier, carry out the sequence from C-terminal to N-terminal on it according to the designed sequence Amino acid condensation reaction, after the last amino acid in the polypeptide ...

Embodiment 2

[0120] According to embodiment 1 result shows the synthetic AL 3 A.AL 5 A.AL 7 A polypeptide can successfully stabilize lipoprotein-like nanoparticles. In this example, the drug-loading ability of lipoprotein-like nanoparticles was studied. to AL 3 A peptide was taken as an example to study. In this embodiment, the steps of the method for preparing lipoprotein-like nanoparticles and the amount of reactants are basically the same as in Example 1, except that 3 μmol DMPC, 0.15 μmol cholesteryl lipid (Cholesteryl oleate, CO for short), 0.2μmol Ir(ppy) 2-DIP in chloroform. Filling the hydrophobic core of lipoprotein-like nanoparticles with the fluorescent and toxic compound Ir(ppy) 2 -DIP. Figure 12 and Figure 13 Show AL 3 A-LNP coated with Ir(ppy)2-DIP can still form lipoprotein-like nanoparticles (AL 3 A-LNP(Ir)). Figure 14 Packaged Ir(ppy) in storage environment as shown 2 -DIP of A-LNP unstable, 48 hours Ir(ppy) 2 -DIP release up to 50%. Package Ir(ppy) 2 -D...

Embodiment 3

[0122] In this example, the -HHHHH- sequence with specific functions was inserted into the circularized structure for functional research. In this example, lipoprotein-like nanoparticles (A(His) 5 A-LNP (Ir)) preparation method steps and the amount of reactants are basically the same as in Example 2, the difference is that in step (6), the helix-loop-helix polypeptide is A(His) 5 a. After step (6), the lipoprotein-like nanoparticles were purified with a 100K ultrafiltration tube to remove free molecules. Detection by DLS and TEM, the results showed that the package Ir(ppy) 2 -A(His) of DIP 5 A-LNP forms nanoparticles with uniform particle size, see Figure 15-Figure 16 . A(His) 5 After A-LNP(Ir) was purified by ultrafiltration, the peptide was quantified, and then incubated with a certain amount of Ni column at room temperature for 1 hour, centrifuged, and the supernatant was sucked for fluorescence detection. Figure 17 It shows that when the cyclic sequence is HHHHH, ...

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Abstract

The invention discloses a polypeptide, a lipoprotein-like nano particle (LNP) and application thereof. The LNP contains at least one phospholipid and at least one polypeptide. A polypeptide series helix-ring-helix structure polypeptide contains at least two amphiphilic alpha helixes, and the two amphiphilic alpha helixes are connected through at least one connecting peptide containing a cyclic structure. The helix part of the polypeptide is imbedded into a lipoprotein-like nano particle surface layer, stable formation of lipid nano particles with uniform size and relatively small particle diameters can be promoted, meanwhile cyclic sequences stretch out of the surfaces of the lipoprotein-like nano particles, and functional sequence insertion is further facilitated, so that multi-functionalization of the LNP is realized. Moreover, the application of the LNP can be further expanded by using an LNP packaged lyophobically functional substance, and for example, the LNP can be used as a drug delivery system; the drug delivery system has the characteristics of being low in toxicity and high in stability, facilitating functionalization and the like, and a simple, convenient and effective means is provided for target killing of cancer cells and cell and tissue imaging.

Description

technical field [0001] The invention specifically relates to a helix-loop-helix structure polypeptide, a lipoprotein-like nanoparticle based on the helix-loop-helix structure polypeptide and its application as a drug-carrying system, belonging to the field of nanobiotechnology. Background technique [0002] In the field of drug delivery, liposomes are widely used in the delivery of cytotoxic drugs, genes, proteins and other substances due to their good biocompatibility, low toxicity and sustained release. Nanoscale liposomes can easily penetrate the vasculature and intercellular spaces of tumor tissues, thereby greatly promoting the delivery and diffusion of drugs in tumor tissues. However, the smaller the particle size of the liposome, the greater the surface tension, which will easily lead to the fusion of the liposome, resulting in the collapse of the structure and the release of the content. In addition, liposomes non-specifically combine with serum proteins, cells, tis...

Claims

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Application Information

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IPC IPC(8): C07K19/00A61K47/42A61K47/28A61K9/51A61P35/00A61P35/02
CPCA61K9/5123A61K9/5169C07K14/775C07K2319/00A61K9/51A61K47/24A61K47/42C07K19/00
Inventor 费浩王乔马晓川贾俊丽
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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