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Polypeptide lipidosome capable of transforming shape in lysosome of tumor cell

A plastid, peptide lipid technology, applied in the field of peptide self-assembly nanosystems, can solve problems such as irritation sensitivity

Active Publication Date: 2017-06-13
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, the lack or decrease in activity of certain phospholipases in lysosomes in tumor cells makes lysosomes fragile and sensitive to stimulation

Method used

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  • Polypeptide lipidosome capable of transforming shape in lysosome of tumor cell
  • Polypeptide lipidosome capable of transforming shape in lysosome of tumor cell
  • Polypeptide lipidosome capable of transforming shape in lysosome of tumor cell

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Utilize benzoic acid and Fmoc-protected L-amino acids (Fmoc-Lys(Boc)-OH, Fmoc-Asp(tBu)-OH, Fmoc-Gly-OH, Fmoc-Ala-OH, purchased from Jill Biochemical (Shanghai) Co., Ltd. ) as a raw material, on dichlorotrityl chloride resin (purchased from Jill Biochemical (Shanghai) Co., Ltd.), under the conditions of coupling reagents and cleavage reagents commonly used in this field, prepared on the resin by solid phase synthesis Polypeptide (the main body is composed of 6 alanines, the C-terminal of the main body is connected to the tumor cell targeting peptide RGD, and the N-terminal of the main body is modified with a benzene ring). After a simple cleavage reaction, the peptide is separated from the resin, and the pure white peptide powder is obtained after subsequent precipitation, washing, and drying.

[0031] The specific experimental process is as follows:

[0032] First, take 1.01 g of dichlorotrityl chloride resin (purchased from Jill Biochemical (Shanghai) Co., Ltd.) to th...

Embodiment 2

[0041] Dissolve 0.1mg of the polypeptide described in Example 1 in 1mL of ultrapure water, adjust the pH to 7.4 with 0.1M HCl solution and 0.1M NaOH solution, sonicate for 1 minute, and let stand for 30 minutes to prepare an electron microscope sample. Observation of the self-assembled morphology shows a liposome-like structure (see figure 1 ).

[0042] Then the pH of the solution was adjusted to 5.0, and left to stand for 30 minutes to prepare an electron microscope sample, which was observed by a transmission electron microscope, showing a nanofiber morphology (see figure 1 ).

Embodiment 3

[0044] Observation of self-assembled nanofibers in cells by transmission electron microscope: Incubate the polypeptide with tumor cell MCF-7, collect the cells after 6 hours, centrifuge at 1000r / min at 4°C for 3 minutes, and remove the old medium on the upper layer. Then the cells were fixed with 2.5% glutaraldehyde and 1% osmic acid, dehydrated with different concentrations of ethanol, and embedded with epoxy resin. Then use Diamond Island to cut the cells into ultra-thin sections with a thickness of 60-90nm, place the sections on copper grids, stain with uranyl acetate and lead citrate, and observe the formation of intracellular fibers under a biological transmission electron microscope (HT7700) ( See figure 2 ).

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Abstract

The invention relates to a self-assembled nano material and in particular to discloses a polypeptide lipidosome capable of transforming shape in a lysosome of a tumor cell. The main body of the polypeptide is a peptide chain formed by six alanines, a benzene ring-containing radial is modified at the terminal N of the peptide chain, and the terminal C of the peptide chain is connected to an RGD polypeptide sequence. The polypeptide under a weakly physiological pH can be self-assembled to form a lipidosome-like structure and is then recognized by the tumor cell and enters the lysosome by means of endocytosis, and the polypeptide responds to the acidic pH in the lysosome. The self-assembled shape lipidosome structure is transformed to nanofibers to induce permeabilization of a lysosome membrane, so that more cathepsins are released to cytoplasms. When the polypeptide lipidosome coats a drug capable of inhibiting lysosome repair or accelerating lysosome to release the cathepsins, the polypeptide lipidosome has a synergistic effect with polypeptide nanofibers, so that the cytotoxicity is enhanced.

Description

technical field [0001] The invention relates to self-assembled nanomaterials, in particular to a polypeptide self-assembled nanosystem with high tumor specificity and lysosome-targeted pH-responsive shape transformation. Background technique [0002] The process of molecular assembly is very common in nature. The coiling and folding of proteins and the double helix of DNA molecules are all biochemical processes under the control of self-assembly. Their delicate and mysterious forces even contain the mystery of the origin of life. The process of molecular self-assembly is a process that is not affected by external forces: it relies on molecular recognition between molecules or between a certain segment of a molecule and another segment, such as hydrogen bonds, van der Waals forces, electrostatic forces, hydrophobic interactions, Non-covalent weak interactions such as π-π stacking effects form molecular aggregates with a specific arrangement order. Once the process of orderly ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K9/127A61K47/42A61K45/00A61P35/00
CPCA61K9/127A61K45/00A61K47/42C07K7/06C07K2319/33
Inventor 赵颖聂广军覃好季天骄
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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