Preparation of brain-targeted bionic nano-drug delivery system and application thereof to brain glioma treatment
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A nano-drug and nano-particle technology, applied in the field of medicine, achieves the effects of low cytotoxicity, reduced toxicity and strong destructive effect
Inactive Publication Date: 2015-11-25
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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[0010] At present, there is no relevant report on the construction of a multi-target nano-drug delivery system that crosses the blood-brain barrier and targets new blood vessels derived from glioma cells and glioma stem cells; Modified Angiopep-2 on the surface apolipoprotein to obtain a new type of nano drug delivery system with good biocompatibility and salinomycin
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Embodiment 1
[0064] Example 1: Linkage of LDL-linked small peptides
[0065] Take 10 mg low-density lipoprotein (Prospec Company, purity 98%), add 10 μg Angiopep-2 (Qiangyao Biotechnology Co., Ltd.), and stir in PBS with pH 8 in the dark for 10 hours.
[0066] After 10 hours, it was placed in deionized water and dialyzed at 4° for 24 hours to remove unbound small peptides.
Embodiment 2
[0067] Embodiment 2: Preparation of low-density lipoprotein nanoparticles loaded with salinomycin sodium
[0068] 10 mg of low-density lipoprotein linked to small peptides prepared in Example 1 was added with 5 mg of starch as a lyoprotectant, and then freeze-dried. Add an appropriate amount of 4 ° pre-cooled heptane, shake vigorously for about 60 seconds, so that the freeze-dried powder and heptane are fully mixed. Centrifuge at 2000rpm for 10min, discard the light yellow supernatant, repeat extraction several times until the supernatant is colorless and discard.
[0069] 2mg salinomycin (TEKU-E company, purity more than 99%) mixed with 0.5mgDHA (Nu-chek company, purity 99%, CAS#6217-54-5) was dissolved in heptane, mixed with 15mg protein starch mixture at 4 °Incubate for 2 hours. The heptane was slowly evaporated in a nitrogen stream on ice until the sample was completely dry. Add an appropriate amount of saline to the dry sample, stir gently to resuspend, and incubate at...
Embodiment 3
[0070] Embodiment 3: the particle diameter of nanoparticle and potential measurement
[0071] The micro-nanoparticles prepared in Example 2 were taken and diluted to 1 mL, and the particle size and zeta potential were measured by dynamic light scattering. The results show that the nanoparticle size is uniform, about 20nm, and the zeta potential is about -5mV, such as figure 1 shown.
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Abstract
The invention relates to the technical field of medicine, in particular to preparation of a brain-targeted bionic nano-drug delivery system and application thereof to brain glioma treatment. The brain-targeted bionic nano-drug delivery system adopts an LDL (low-density lipoprotein) and DHA (docosahexaenoic acid) compound as a vector to modify Angiopep-2 on surface apolipoprotein and encapsulate salinomycin. The brain-targeted bionic nano-drug delivery system has the advantages of good biocompatibility and no immunogenicity; under the action of transcytosis mediated by LRP-1 (low-density lipoprotein receptor-related protein 1) expressed in blood brain barrier, the brain-targeted bionic nano-drug delivery system targets to penetrate the blood brain barrier actively; after entering the brain, the brain-targeted bionic nano-drug delivery system targets spongioblastoma by means of common mediation of an LDLR (low-density lipoprotein receptor) and an LRP-1 receptor, and kills tumor cells, tumor stem cells and multiple target points of tumor angiogenic blood vessels. The preparation of the brain-targeted bionic nano-drug delivery system and application thereof to brain glioma treatment provide a safer, more efficient and atraumatic drug-delivery way for treatment of tumors of the central nervous system.
Description
Technical field: [0001] The invention relates to the technical field of medicine, in particular to a bionic nano drug delivery system for actively targeting brain glioma to deliver drugs and a preparation method thereof. The drug delivery system carrier of the present invention is a natural small particle size lipoprotein, which is modified by a functional peptide with active targeting, through the low-density lipoprotein receptor-related transmembrane receptor protein LRP expressed on the blood-brain barrier -1 mediated through the blood-brain barrier, while targeting glioma mediated by low-density lipoprotein receptor and LRP-1, targeting glioma cells, glioma stem cells and glioma neovascularization Point killing, to achieve therapeutic effect. Background technique: [0002] Glioma is the most common malignant tumor of the central nervous system, occurring in the neuroectoderm, derived from astrocytes or oligodendrocytes, accounting for 35-60% of intracranial tumors. Acc...
Claims
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