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Peptide functionalized metal-loaded porphyrin phase-change nanoparticle and preparation method and application thereof

A metalloporphyrin and nanoparticle technology, applied in the field of biomedicine, can solve the problems of reducing the effect of tumor diagnosis and treatment, limited tumor cell killing effect, and inability to realize dual-modal imaging

Active Publication Date: 2020-09-18
CHONGQING MEDICAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the above-mentioned technical solution has the following defects: the reagent cannot achieve the effect of ultrasound / nuclear magnetic resonance dual-mode imaging, which reduces the effect of tumor diagnosis and treatment; liquid fluorocarbons have limited tumor cell killing effect through micro-explosion, and cannot achieve effective tumor treatment

Method used

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  • Peptide functionalized metal-loaded porphyrin phase-change nanoparticle and preparation method and application thereof
  • Peptide functionalized metal-loaded porphyrin phase-change nanoparticle and preparation method and application thereof
  • Peptide functionalized metal-loaded porphyrin phase-change nanoparticle and preparation method and application thereof

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preparation example Construction

[0068] Embodiment 1-embodiment 4 is the preparation process of nanoparticle, wherein mainly used reagent and instrument are as follows:

[0069] Olympus IX71 optical microscope, Nikon AIR laser confocal microscope, Zeta SIZER 3000HS Malvern particle size analyzer, Hitachi H-7600 transmission electron microscope, SHIMADZU UV-2550 ultraviolet spectrophotometer, Sonics&Materials acoustic vibration instrument, Mylab 90 ultrasonic diagnostic instrument ( LA523 linear array probe, frequency 4 ~ 10MHz), Verio-40690 Siemens 3.0T magnetic resonance instrument. Dipalmitoylphosphatidylcholine (DPPC, Avanti), dipalmitoylphosphatidylglycerol (DPPG, Avanti), distearoylphosphatidylethanolamine (DSPE, Avanti), cholesterol (CH, Sigma), blood Porphyrin monomethyl ether-gadolinium (HMME-Gd, Medicin Biotechnology Co., Ltd.), perfluoropentane (PFP, Strem Chemicals Company), chloroform (Chongqing Chuandong Chemical Co., Ltd.), dimethyl sulfoxide (DMSO, Chongqing Chuandong Chemical Co., Ltd.), tumo...

Embodiment 1

[0070] Example 1: Preparation of peptide-functionalized metalloporphyrin phase-change nanoparticles (PFP@tLyP-1-LIP-H(Gd))

[0071] Step (1): DSPE-PEG3400-mal modified with tLyP-1 was used. tLyP-1 was connected with DSPE-PEG3400-mal by maleimide method to obtain DSPE-PEG3400-tLyP-1, which was analyzed and purified. Among them, tLyP-1 was synthesized by Shanghai Qiangyao Biotechnology Co., Ltd. using solid-phase method, and the DSPE modified by tLyP-1 was completed by Chongqing Punovi Biotechnology Co., Ltd.

[0072] Step (2): Preparation of PFP@tLyP-1-LIP-H(Gd).

[0073] Weigh 10mgDPPC, 4mgDSPE-PEG3400-tLyP-1, 3mgDPPG, 3mgCH, 2mgHMME-Gd, and dissolve the above materials in 10ml chloroform to obtain a film-forming system. Under the condition of a water bath at 50°C, the film-forming system was evaporated in vacuum for 1 hour to form a film, and the film was hydrated with 4ml of PBS to obtain a hydration system. Under the condition of ice bath, 400 μL of PFP was added to the ...

Embodiment 2

[0074] Example 2: Preparation of metalloporphyrin-loaded phase-change nanoparticles (PFP@LIP-H(Gd))

[0075] Weigh 10mgDPPC, 4mgDSPE, 3mgDPPG, 3mgCH, 2mgHMME-Gd, fully dissolve in 10ml of chloroform, and evaporate under vacuum for 1 hour in a water bath at 50°C to form a lipid film, and then hydrate with 4ml of deionized water. Under ice-bath conditions, 400 μL of PFP was added, and a vibrator with a power of 100 W (ON 5s, OFF 5s) was used to vibrate for 6 minutes to obtain a system containing PFP@LIP-H(Gd)s. The obtained nanoparticles were centrifuged at low temperature (8000r / min, 5min), and then the solid phase was washed with PBS, repeated 3 times, and finally resuspended with 4ml of PBS to obtain PFP@LIP-H(Gd). Protect from light throughout the preparation process. The particle size of the nanoparticles prepared by this scheme is (262.53 ± 1.98) nm, the potential is (29.17 ± 0.929) mV, and the dispersion coefficient PDI (0.0143 ± 0.00208) (results see image 3 , Figur...

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Abstract

The invention belongs to the field of biomedicine, relates to a nanoparticle and a preparation method and application thereof, and in particular relates to a peptide functionalized metal-loaded porphyrin phase-change nanoparticle and a preparation method and application thereof. The nanoparticle comprises a shell membrane formed by liposome, and liquid fluorocarbon encapsulated in the shell membrane, wherein a tumor homing cell-penetrating peptide is covalently attached to the shell membrane, and the inside of the lipid bilayer of the liposome is encapsulated with a contrast agent. The nanoparticle has the function of penetrating the tumor blood vessel barrier and the tumor interstitial barrier, can penetrate deep into tumor tissues, and more effectively realizes the diagnosis and treatment of tumors. The nanoparticle of the scheme can be applied in the development and preparation of drugs for tumor diagnosis or treatment.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to nanoparticles and a preparation method and application thereof, in particular to a peptide-functionalized metalloporphyrin-loaded phase-change nanoparticle and a preparation method and application thereof. Background technique [0002] The integration of cancer diagnosis and treatment is a new technology integrating cancer diagnosis and treatment. This technology integrates substances with tumor diagnosis and treatment functions into a nanometer platform (nanoparticles) at the same time, and obtains nano preparations with both diagnosis and treatment functions. The nano-preparation can realize early diagnosis of cancer, precise tumor localization, in situ treatment of tumor, and real-time monitoring during treatment. [0003] Chinese patent CN104826140A (preparation method and application of a drug-loaded silicon lipid ultrasonic contrast agent) discloses an ultrasonic contrast agent, whi...

Claims

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Application Information

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IPC IPC(8): A61K49/22A61K49/18A61K49/10A61K49/00A61K41/00A61P35/00
CPCA61K49/223A61K49/1812A61K49/106A61K49/0084A61K49/0036A61K49/0002A61K41/0033A61P35/00
Inventor 任建丽周志益罗远利乔斌王志刚冉海涛李攀郝兰曹阳
Owner CHONGQING MEDICAL UNIVERSITY
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