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Controllable thermosensitive peptide nano valve modified core-shell mesoporous silica nano-particles as well as preparation method and application thereof

A technology of mesoporous silica and nanoparticles, which is applied in the direction of medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, and can solve problems that are only applicable to certain organisms or organisms. In some local locations, it is difficult to achieve release, etc., to achieve the effect of controlled release and mild release conditions

Active Publication Date: 2018-05-18
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To date, several MSN-based systems have been proposed using short peptides as nanovalves for controlled release, for example, there are currently short peptide-MSN systems with enzyme responsiveness (e.g., elastase, thermolysin) , as well as reports of short peptide-MSN systems with redox responsiveness (usually glutathione), if these short peptide-MSN systems are used in biological applications, the triggering of specific triggers is required to achieve the inclusion of entrapped substances. release, but this trigger based on enzymes or redox reactions may only be applicable to certain organisms or certain local locations of organisms, and it is difficult to achieve effective and controllable release

Method used

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  • Controllable thermosensitive peptide nano valve modified core-shell mesoporous silica nano-particles as well as preparation method and application thereof
  • Controllable thermosensitive peptide nano valve modified core-shell mesoporous silica nano-particles as well as preparation method and application thereof
  • Controllable thermosensitive peptide nano valve modified core-shell mesoporous silica nano-particles as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] In this example, the preparation of core-shell mesoporous silica nanoparticles (SPNC@MSN-PEP) modified by controllable thermosensitive peptide nanovalve is as follows:

[0063] (1) Preparation of manganese-doped magnetic iron oxide (MnFe 2 o 4 ) nanoparticles

[0064] 2mmol Fe(acac) 3 , 1mmol Mn(acac) 2 , 10mmol 1,2-dodecanediol, 6mmol oleic acid and 6mmol oleylamine were dissolved in 20mL benzyl ether, heated to 200°C under nitrogen atmosphere and vigorous stirring, then kept at 200°C for 2h, and then heated at 298°C ℃ reflux reaction for 1h to obtain MnFe-containing 2 o 4 The reaction liquid of nanoparticle, this reaction liquid is cooled to room temperature, adds in 40mL ethanol and precipitates MnFe 2 o 4 nanoparticles, MnFe by centrifugation 2 o 4 The nanoparticles were further separated and redispersed in 10 mL of n-hexane for storage.

[0065] Detection of MnFe by Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) 2 o 4 The molar ratio...

Embodiment 2

[0098] In this example, the thermosensitive release behavior of MSN-PEP prepared in Comparative Example 1 under conventional heating conditions, and the thermosensitive release behavior of SPNC@MSN-PEP prepared in Example 1 and under superparamagnetic heating conditions were investigated.

[0099] (1) Add 15mg of MSN-PEP to 1.5mL of 1mmol / L aqueous solution of fluorescein sodium, and ultrasonically disperse evenly. Considering the self-assembly properties and CD data of amphiphilic short peptides at room temperature, set the temperature at 50°C For pore opening and dye loading, the test tube containing MSN-PET and sodium fluorescein aqueous solution was incubated in a water bath at 50 °C for 2 h to load sodium fluorescein on MSN-PEP, and then the test tube was left at room temperature for 12 h In order to ensure the re-self-assembly of the grafted amphiphilic short peptide on MSN, the drug-loaded MSN-PEP was obtained.

[0100]3 mg of drug-loaded MSN-PEP was dispersed in 250 μL...

Embodiment 3

[0105] In this example, the anticancer drug daunorubicin (DNR) is loaded on SPNC@MSN-PEP, and the steps are as follows:

[0106] Add 15mg of SPNC@MSN-PEP to 1.5mL of 2mg / mL DNR aqueous solution, ultrasonically disperse evenly, and incubate the test tube containing SPNC@MSN-PEP and DNR aqueous solution in a water bath at 50°C for 2h to load DNR on SPNC @MSN-PEP, and then let the test tube stand at room temperature for 12h to ensure that the grafted amphiphilic short peptide on SPNC@MSN-PEP re-assembles, and the DNR-loaded SPNC@MSN-PEP is obtained, denoted as DNR@SPNC@ MSN-PEP.

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Abstract

The invention provides controllable thermosensitive peptide nano valve modified core-shell mesoporous silica nano-particles which consist of core-shell type mesoporous silica nano-particles and amphiphilic oligopeptide grafted on the surfaces of the core-shell type mesoporous silica nano-particles by long-chain amidogen. The core-shell type mesoporous silica nano-particles consist of superparamagnetic nano-particle cores and mesoporous silica shell layers coating the superparamagnetic nano-particle cores; the amphiphilic oligopeptide grafted on the surfaces of the core-shell type mesoporous silica nano-particles by the long-chain amidogen can respond to changes of a temperature to self-assemble or relieve self-assembling so as to enable pore passages on the mesoporous silica shell layers to be in a blocked or opening state; the amphiphilic oligopeptide has an amino acid sequence of Boc-Phe Phe Gly Gly-COOH; the long-chain amidogen is (with reference to the specification) or (with reference to the specification). The invention further provides a preparation method of the controllable thermosensitive peptide nano valve modified core-shell mesoporous silica nano-particles and application of the controllable thermosensitive peptide nano valve modified core-shell mesoporous silica nano-particles as a drug carrier.

Description

technical field [0001] The invention belongs to the field of drug carrier materials, and relates to a core-shell mesoporous silica nanoparticle modified by a controllable thermosensitive peptide nanovalve and a preparation method thereof, and a core-shell mesoporous silica nanoparticle modified by the controllable thermosensitive peptide nanovalve. Applications of silica nanoparticles as drug carriers. Background technique [0002] Mesoporous silica nanoparticles (MSNs) have been widely studied as drug carriers due to their large surface area, porous structure, and good biocompatibility. Short peptides have been widely exploited due to their tunable functions, biodegradability, and good biocompatibility. Amphiphilic peptides have attracted more and more attention as building blocks of molecular design based on their self-assembly properties, and have broad application prospects in three-dimensional cell culture, hemostasis, and drug delivery. To date, several MSN-based sys...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K41/00A61K47/02A61K47/04A61K47/18A61K31/704A61P35/00
CPCA61K9/0009A61K9/5115A61K9/5123A61K31/704A61K41/00
Inventor 阮丽萍梅显斌
Owner SICHUAN UNIV
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