WO2013135103A1 - Mélittine porteuse de polypeptide, mélittine porteuse de nanoparticules et utilisation associée - Google Patents

Mélittine porteuse de polypeptide, mélittine porteuse de nanoparticules et utilisation associée Download PDF

Info

Publication number
WO2013135103A1
WO2013135103A1 PCT/CN2013/000279 CN2013000279W WO2013135103A1 WO 2013135103 A1 WO2013135103 A1 WO 2013135103A1 CN 2013000279 W CN2013000279 W CN 2013000279W WO 2013135103 A1 WO2013135103 A1 WO 2013135103A1
Authority
WO
WIPO (PCT)
Prior art keywords
melittin
polypeptide
carrying
nanoparticle
nanoparticles
Prior art date
Application number
PCT/CN2013/000279
Other languages
English (en)
Chinese (zh)
Inventor
骆清铭
张智红
黄川�
Original Assignee
华中科技大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 华中科技大学 filed Critical 华中科技大学
Publication of WO2013135103A1 publication Critical patent/WO2013135103A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • C07K14/43563—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects
    • C07K14/43572—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects from bees
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Definitions

  • the invention belongs to the field of biological sciences and pharmaceutical carriers, and in particular relates to a polypeptide carrying melittin, a nanoparticle carrying melittin and an application thereof. Background technique
  • Melittin (GIGAVLKVLTTGLPALISWIKRKRQQ) is an amphiphilic alpha-helical polypeptide that is the main active component of bee venom, accounting for 40% - 60% of its dry weight. Melittin is highly active, has a broad-spectrum antibacterial function, and can exert its effects in a very short period of time. Its efficiency is hundreds of times higher than that of ordinary antibiotics. Melittin is highly destructive to the cell membrane structure, including the plasma membrane and the membrane structure of some organelles in the cell.
  • melittin can play a significant role in the treatment of tumors.
  • melittin can also inhibit the proliferation of HIV by inhibiting the expression of HIV-1 gene and the activity of LTR; it also has anti-inflammatory and analgesic effects, and the analgesic intensity is 40% of morphine.
  • melittin Long-lasting analgesic, anti-inflammatory activity is more than 100 times that of hydrocortisone, does not cause immunosuppression; melittin can also regulate the release of adrenocortical hormone, to achieve anti-rheumatic, rheumatoid arthritis; In addition, melittin can also cause neuroendocrine reactions, enhance the body's anti-radiation effect and prevent platelet aggregation and anti-thrombosis. In conclusion, melittin has broad application prospects in the treatment of various diseases.
  • melittin due to the nature of melittin itself, it is difficult to apply it directly to the treatment of diseases in living organisms. Because the melittin rapidly binds to the red blood cells after being injected into the blood vessel, the cell membrane is destroyed, resulting in a strong hemolysis reaction. Moreover, the direct application of melittin to living body treatment may cause damage to normal cells of the body, and bring about great toxic and side effects. In addition, the half-life of melittin in the body Very short, rapid metabolism, and not conducive to clinical disease treatment.
  • nanocarriers are gradually being paid attention to.
  • the use of nanoparticles to carry melittin is a method that effectively avoids its toxic side effects.
  • liposome carries melittin
  • electron microscopy results show that the structure of the liposome changes greatly after loading melittin, and some may be degraded.
  • some researchers have proposed a more stable PEG-modified disc-shaped particle using liposome to carry melittin, but it has not been applied to living therapy.
  • Some researchers have used PLGA [poly(D, L-lactide-co-glycolide acid)] particles to carry high encapsulation rates of melittin, but they have only carried out in vitro comparative experiments and have not continued to .
  • Some of the other nanoparticles that carry melittin are also greatly limited because their hemolytic properties are not improved.
  • PFC perfluorocarbon
  • the melittin nanoparticles can achieve specific enrichment of tumors after modification of the targeting group.
  • PFC particles have a large particle size, between 200 and 300 nm, and cannot pass through the gaps of dense reticular collagen fibers (20-40 nm) in solid tumors, and it is difficult to effectively diffuse into the interior of the tumor, especially Solid tumors that are not rich in blood vessels are difficult to achieve the desired therapeutic effect.
  • PFC particles will change with the binding amount of melittin, and it may interact with the charged proteins in the blood vessels in vivo.
  • PFC particles are not suitable for the coordinated loading of melittin and traditional anticancer drugs. .
  • the object of the present invention is to provide a polypeptide carrying melittin and to solve the above problems Its nanoparticles, preparation methods and applications thereof.
  • the nanoparticle prepared by using the polypeptide carrying melittin can effectively reduce the toxic side effects of melittin on the body, and specifically plays a role in a diseased region such as a tumor, and can be applied to clinical treatment.
  • a polypeptide carrying melittin which is formed by a chain connection of an alpha helix polypeptide, a linker sequence and a melittin peptide in the form of a covalent bond.
  • amino acid sequence of the alpha helix polypeptide is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethy
  • amino acid sequence of the linker sequence is GSG.
  • a nanoparticle carrying a melittin which comprises the organic combination of a polypeptide carrying melittin, a phospholipid, and a cholesterol ester according to claim 1.
  • the phospholipid is DMPC ( 1,2-dimyristoyl-sn
  • nanoparticle carrying melittin which is effective for reducing the toxic side effects of melittin on the body, and specifically functions in a diseased region including a tumor, and can be applied to clinical treatment.
  • the average particle diameter of the nanoparticles measured by dynamic laser light scattering method is about 12 nm.
  • the results of electron microscopy show that the nanoparticles have uniform particle size, good dispersion and no aggregation.
  • the raw materials used in the preparation of the nanoparticles are phospholipids, cholesterol lipids and polypeptides carrying melittin, which have been used in clinical or clinical trials and have good biocompatibility.
  • the drug encapsulation efficiency is greater than 80%, which complies with the requirements of the Pharmacopoeia of the People's Republic of China for microcapsule preparations; and compared with the free melittin, the nanoparticles carrying melittin are prepared by using the polypeptide carrying melittin The drug encapsulation rate increased by 18 times.
  • the small nano-size can freely pass through the dense reticular collagen gap of the solid tumor to reach the core of the tumor, thereby effectively killing the tumor cells, and can effectively avoid the resistance of the tumor cells.
  • nanoparticles carrying melittin can also be loaded with dye molecules and drug molecules for disease diagnosis and treatment at the core, or other types can be loaded at the same time.
  • the targeted polypeptide or therapeutic polypeptide achieves the synergistic or synergistic therapeutic effect of the disease.
  • Figure 1 is a dual-band absorption-time curve of a low-dose nanoparticle loaded with melittin prepared by a FPLC (Fast Protein Liquid chromatography) system;
  • Figure 2 is a two-band absorption-time curve of the FPLC system for purifying nanoparticles carrying melittin
  • Figure 3 is a double-band absorption-time curve of a FPLC system for purifying large doses of nanoparticles carrying melittin;
  • Figure 4 is a three-band absorption-time curve of the FPLC system purifying the core loaded with the fluorescent dye DiR-BOA carrying melittin nanoparticles;
  • Figure 5 is a three-band absorption-time graph of the FPLC system purifying core loaded with Fluo-BOA nanoparticles carrying melittin;
  • Figure 6 is a graph showing the results of nanoparticle size of nanoparticles carrying melittin using a dynamic laser light scattering (DLS) system;
  • DLS dynamic laser light scattering
  • Figure 7 is a transmission electron microscope image of nanoparticles carrying melittin
  • Figure 8 is a comparison of erythrocyte hemolysis test of nanoparticles carrying melittin and free melittin;
  • Figure 9 is a comparison of the ability of nanoparticles carrying melittin and free melittin to inhibit proliferation of various tumor cells
  • Figure 10 is a graph showing the time-tumor volume of the growth of B16 tumors in C57BL/6 mice by nanoparticles carrying melittin;
  • Figure 11 is a graph showing the tumor block after exfoliation of the B16 tumor in the C57BL/6 mice on the 13th day after the peeling of the B16 tumor in the C57BL/6 mice;
  • Figure 12 is a blood biochemical and blood cell index on day 13 of a mouse model carrying B16 tumor treated with nanoparticles of melittin;
  • Figure 14 is a fluorescence imaging result of SDS-PAGE electrophoresis after the core-loaded fluorescent dye Fluo-BOA carrying melittin nanoparticles were incubated for 3 h under different conditions;
  • Figure 15 is a statistical diagram of the flow cytometry analysis using Annexin V-FITC and PI staining after 3 hours of action of melittin nanoparticles and B16 tumor cells;
  • Figure 16 shows the real-time imaging results of the interaction of nanoparticles carrying melittin with B16 tumor cells, in which the nuclei were labeled with Hochest 33342, the cytoplasm was labeled with the red fluorescent protein Katushka S158A, and the melittin was labeled with FITC.
  • a polypeptide carrying melittin which is a series of covalent bonds formed by an alpha helix polypeptide, a linker sequence and a melittin.
  • the amino acid sequence of the ⁇ -helical polypeptide in this example is:
  • the amino acid sequence of the ligated sequence is GSG, melittin
  • the amino acid sequence is: GIGAVLKVLTTGLPALISWIKRKRQQ.
  • the amino acid sequence of the polypeptide carrying melittin is as set forth in SEQ ID NO. 1 of the Sequence Listing.
  • test tube was placed in a vacuum desiccator and dried under vacuum for 1 h ;
  • FIG. 1 is a two-band absorption-time plot of a FPLC system for purifying small doses of nanoparticles carrying melittin.
  • Nanoparticles carrying melittin were prepared in small amounts using 0.19 ⁇ ⁇ 1 to carry the melittin polypeptide.
  • the 215 nm absorption curve shown in Figure 1 is 1/5 of the actual value.
  • Peak 1 There are three peaks in Figure 1, which are defined as Peak 1, 2, and 3, respectively, according to the chronological order; Peak 2 is a nanoparticle carrying melittin, and Peak 3 is a free polypeptide. Peak 2 has an integrated area of 80.3% of the total area and a free polypeptide content (Peak 3 area) of 8.74%.
  • Figure 2 is a two-band absorption-time plot of the FPLC system for purification of melittin nanoparticles. The melittin nanoparticles were prepared in small amounts using 0.19 ⁇ ⁇ 1 ⁇ -helix polypeptide and 0.19 ⁇ 1 melittin. The 215 nm absorption curve shown in the figure is 1/5 of the actual value.
  • FIG. 3 is a two-band absorption-time plot of the FPLC system for the purification of large doses of nanoparticles carrying melittin. Nanoparticles carrying melittin were prepared in large quantities using 1.9 ⁇ of the polypeptide carrying melittin.
  • the preparation dose shown in Fig. 1 is magnified 10 times year-on-year, and the 215 nm absorption curve value shown in the figure is 1/5 of the actual value. ).
  • the area of Peak 2 in Figure 3 is 79.5%, which is similar to the yield in a small amount of preparation, indicating that the yield of the method is not significantly reduced during the amplification process, and can be subjected to large-scale preparation and purification.
  • the nanoparticles carrying melittin it is also possible to carry a fluorescent dye in its core during preparation.
  • the ratio of raw materials is: 3 mol DMPC, 0.1 ⁇ CO, 0.3 ⁇ DiR-BOA (a modified near-infrared fluorescent dye with excitation and emission wavelengths of 748 nm and 780 nm, respectively) and 0.57 ⁇ peptide carrying melittin
  • DiR-BOA a modified near-infrared fluorescent dye with excitation and emission wavelengths of 748 nm and 780 nm, respectively
  • the 215 nm absorption curve shown in Figure 4 is 1/10 of the original value.
  • FIG. 8 See Figure 8 for a comparison of the hemolysis properties of the nanoparticles carrying melittin prepared in Example 1 with free melittin.
  • Figure 8 shows that the nanoparticle carrying melittin has a hemolysis rate of less than 10% at a concentration of meptopeptide of 60 ⁇ M, while the free melittin is at 1 ⁇ is close to 100%. It is proved that the nanoparticles carrying melittin can effectively reduce the hemolysis performance of melittin, and will not destroy red blood cells after intravenous injection, which provides a basis for its application in living therapy.
  • Nanoparticles carrying melittin prepared in Example 1 were treated in vivo in a tumor model: A B 16 subcutaneous tumor model was constructed. B 16 cells were digested, and the cells were counted by rinsing twice with sterilized PBS, and finally the cell concentration was set to 8 x 106/L. C57BL/6 mice were anesthetized, and the tumor cell solution was injected subcutaneously into the left leg of the mouse, and the injection volume was 100 ⁇ l. The date of inoculation was set to day 0, and the subsequent dates were recorded as days 1, 2, and 3, respectively. On the 4th day, the rats were randomly grouped according to their needs, and the recommended number of each group was not less than 5.
  • the tail vein injection was started on the 5th day. Each mouse was labeled prior to injection, and the quality of each mouse was weighed and recorded in a pre-established form.
  • the I.v. therapy group required a tail vein injection of ⁇ -melittin-NP at a dose of 20 mg/kg (polypeptide) with an injection volume of 0.2 ml/10 g.
  • the I.p. therapy group was injected intraperitoneally with a-melittin-NP at a dose of 20 mg/kg (polypeptide) in an injection volume of 0.3 ml/10 g.
  • the NP Control group served as an empty vector control, and the concentration of the injection was determined based on the phospholipid concentration, which was required to be consistent with the phospholipid concentration of the Therapy group.
  • mice treated with nanoparticles treated with melittin were examined and participated in Figure 12.
  • the experimental results showed that the nanoparticles carrying melittin did not produce significant toxicity to the liver and kidney of mice, and the blood cell parameters were not significantly different from the control, which confirmed its good biocompatibility.
  • the three types of substances (phosphorus esters, cholesterol oleate, and polypeptides) prepared in the preparation of the melittin-producing nanoparticles prepared in Example 1 have been clinically applied.
  • Doxil is a drug that uses liposomes to encapsulate doxorubicin for the treatment of Kaposi's sarcoma.
  • the US FDA has approved Doxil for the treatment of ovarian cancer and multiple myeloma.
  • Cholesterol is a substance that exists in the human body and has good biosafety.
  • Lugua peptide is a good drug for the treatment of fractures.
  • the osteoinductive polypeptide-like biological factor which is a main component of the drug can effectively promote the synthesis of bone-derived growth factors which affect bone formation and absorption in the body.
  • Lugua polypeptide injection can significantly promote bone healing and new bone formation, regulate bone metabolism, and has anti-inflammatory and analgesic effects. It has a definite effect on fracture non-union osteoporosis, no obvious adverse reactions, and rheumatoid arthritis. Soft tissue injury is excellent.
  • FIGs. 15 and 16 are a comparison of classical methods using the method of Annexin V-FITC/PI staining to demonstrate the pattern of cell death.
  • Figure 15 shows that when the concentration of nanoparticles carrying melittin is low, cell death is more likely to be apoptosis, but as the concentration of the incubation increases, the ratio of necrotic cells The regular meeting will increase significantly.
  • Figure 16 is a graph showing the results of real-time imaging of nanoparticles carrying melittin (polypeptide labeled with FITC) and B16 cells labeled with red fluorescent protein Katushka S158A by laser confocal microscopy. It can be clearly seen in Fig. 16 that as time progresses, the red signal in the cell gradually weakens until it disappears, indicating that the cell membrane is being destroyed by the nanoparticles carrying melittin. Then, the nucleus collapses and the green signal in the cytoplasm gradually increases and accumulates on some membrane systems. It has again been demonstrated that nanoparticles carrying melittin kill cells by directly causing cell necrosis.
  • melittin polypeptide labeled with FITC
  • red fluorescent protein Katushka S158A red fluorescent protein

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Insects & Arthropods (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Dispersion Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biomedical Technology (AREA)
  • Nanotechnology (AREA)
  • Optics & Photonics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une mélittine porteuse de polypeptide, une mélittine porteuse de nanoparticule et l'utilisation de ceux-ci, qui appartient au domaine de la bioscience et des vecteurs de médicament. Le peptide est formé en connectant un polypeptide hélix, une séquence de coupleur et de la mélittine en série par des liaisons covalentes; la nanoparticule est formée en combinant une mélittine porteuse de polypeptide, de la phospholipide et de l'ester de cholestérol. La nanoparticule préparée à partir de la mélittine porteuse de polypeptide peut efficacement réduire les effets secondaires et toxiques de la mélittine sur les organismes et joue spécifiquement un rôle dans les zones de maladie telles que les tumeurs etc; ainsi, peut être utilisée dans le traitement clinique.
PCT/CN2013/000279 2012-03-13 2013-03-13 Mélittine porteuse de polypeptide, mélittine porteuse de nanoparticules et utilisation associée WO2013135103A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201210064564.2 2012-03-13
CN2012100645642A CN103073646A (zh) 2012-03-13 2012-03-13 一种运载蜂毒肽的多肽、运载蜂毒肽的纳米颗粒及其应用

Publications (1)

Publication Number Publication Date
WO2013135103A1 true WO2013135103A1 (fr) 2013-09-19

Family

ID=48150360

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2013/000279 WO2013135103A1 (fr) 2012-03-13 2013-03-13 Mélittine porteuse de polypeptide, mélittine porteuse de nanoparticules et utilisation associée

Country Status (2)

Country Link
CN (1) CN103073646A (fr)
WO (1) WO2013135103A1 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104784677A (zh) * 2014-05-13 2015-07-22 东北师范大学 蜂毒肽在制备抑制乳腺癌细胞侵润转移药物中的应用
CN106699896B (zh) * 2016-12-05 2020-06-05 华中科技大学同济医学院附属协和医院 一种可自组装成水凝胶的肿瘤杀伤性多肽及其应用
CN106632688B (zh) * 2016-12-23 2020-06-05 华中科技大学同济医学院附属协和医院 一种用于修饰微泡的多肽以及靶向gbm的药物制剂
CN109692327B (zh) * 2017-10-23 2022-04-08 华中科技大学 一种运载蜂毒肽的纳米颗粒的应用
CN109692326A (zh) * 2017-10-23 2019-04-30 华中科技大学 一种蜂毒脂质纳米颗粒的应用
CN109513000A (zh) * 2019-01-14 2019-03-26 华中科技大学同济医学院附属协和医院 一种运载蜂毒肽的光敏性纳米载体制备方法及应用
CN113499321B (zh) * 2021-06-10 2022-06-10 南方医科大学 一种微马达载体及其制备方法与应用
CN113559241A (zh) * 2021-07-22 2021-10-29 上海市宝山区中西医结合医院(上海中医药大学附属曙光医院宝山分院) 一种蜂毒肽脂质纳米颗粒及其制备方法和应用
CN114099692B (zh) * 2021-11-30 2023-06-09 西南大学 一种抗菌肽-细胞膜复合物、制备方法和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009070210A2 (fr) * 2007-11-27 2009-06-04 Abbott Cardiovascular Systems Inc. Libération prolongée de peptides mimétiques de l'apo a-i, et méthodes de traitement associées
CN102123737A (zh) * 2008-06-13 2011-07-13 西马生物医学计划公司 用于生物活性化合物施用的轭合物

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6037323A (en) * 1997-09-29 2000-03-14 Jean-Louis Dasseux Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders
CN1704431A (zh) * 2004-06-04 2005-12-07 中国人民解放军第三军医大学第一附属医院 蜂毒肽及其应用
CN1754960A (zh) * 2004-10-02 2006-04-05 青岛大学 蜂毒素与基因变构白细胞介素2嵌合体蛋白
CN101406691A (zh) * 2008-11-17 2009-04-15 沈阳药科大学 用于口服给药的蜂毒肽复合物纳米粒及其制备方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009070210A2 (fr) * 2007-11-27 2009-06-04 Abbott Cardiovascular Systems Inc. Libération prolongée de peptides mimétiques de l'apo a-i, et méthodes de traitement associées
CN102123737A (zh) * 2008-06-13 2011-07-13 西马生物医学计划公司 用于生物活性化合物施用的轭合物

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
EPAND, RM. ET AL.: "An apolipoprotein AI mimetic peptide: membrane interactions and the role of cholesterol", BIOCHEMISTRY, vol. 43, September 2004 (2004-09-01), pages 5073 - 5083, XP055056936, DOI: doi:10.1021/bi049786u *
SOMAN, N.R. ET AL.: "Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 119, no. 9, September 2009 (2009-09-01), pages 2830 - 2842, XP002755693, DOI: doi:10.1172/JCI38842 *

Also Published As

Publication number Publication date
CN103073646A (zh) 2013-05-01

Similar Documents

Publication Publication Date Title
WO2013135103A1 (fr) Mélittine porteuse de polypeptide, mélittine porteuse de nanoparticules et utilisation associée
Wang et al. Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury
CN102302784B (zh) 一种肿瘤化疗药物制剂及其制备方法
Li et al. Nanomedicine-based cancer immunotherapies developed by reprogramming tumor-associated macrophages
Chen et al. Living leukocyte‐based drug delivery systems
Wang et al. CXCR4-guided liposomes regulating hypoxic and immunosuppressive microenvironment for sorafenib-resistant tumor treatment
WO2018041261A1 (fr) Médicament thérapeutique antitumoral
CN102552105B (zh) 一种级联脑部靶向药物递送系统及其制备方法和用途
CN100431609C (zh) 注射用的整合素配体修饰的载抗癌药的长循环脂质体
Zhao et al. Calcium phosphate nanoneedle based gene delivery system for cancer genetic immunotherapy
WO2013181934A1 (fr) Polypeptide doté d'une fonction de diagnostic et de thérapie ciblés synergiques du carcinome nasopharyngé, nanoparticules le portant et son utilisation
CN105873941A (zh) 生存素导向的癌症疫苗治疗
Sawant et al. Cancer research and therapy: Where are we today
CN108187061B (zh) 靶向棕色脂肪组织的递药系统
CN109223827A (zh) 水溶性的富勒烯结构在制备治疗肺纤维化的药物中的应用
Xu et al. Antisenescence ZIF-8/resveratrol Nanoformulation with potential for enhancement of bone fracture healing in the elderly
CN108143719B (zh) 一种携载多肽的纳米脂质体及其制备方法和应用
Gui et al. Bone-Targeting Peptide and RNF146 Modified Apoptotic Extracellular Vesicles Alleviate Osteoporosis
Xu et al. Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy
CN108743964A (zh) 一种狂犬病毒糖蛋白衍生肽修饰的脑靶向核酸递送载体及其应用
CN117298065A (zh) 一种多功能纳米免疫调节制剂及其制备方法与免疫系统重塑的抗肿瘤应用
Xiao et al. Supramolecular Peptide Amphiphile Nanospheres Reprogram Tumor‐associated Macrophage to Reshape the Immune Microenvironment for Enhanced Breast Cancer Immunotherapy
Zhang et al. Peptide nano ‘bead-grafting’for SDT-facilitated immune checkpoints blocking
Fan et al. Polysialic acid self-assembled nanocomplexes for neutrophil-based immunotherapy to suppress lung metastasis of breast cancer
Zhang et al. The protective effect of puerarin-loaded mesoporous silicon nanoparticles on alcoholic hepatitis through mTOR-mediated autophagy pathway

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13760291

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13760291

Country of ref document: EP

Kind code of ref document: A1