CN1772300A - 磁热疗用纳米磁粉－抗cea抗体靶向药物 - Google Patents
磁热疗用纳米磁粉－抗cea抗体靶向药物 Download PDFInfo
- Publication number
- CN1772300A CN1772300A CN200510095001.XA CN200510095001A CN1772300A CN 1772300 A CN1772300 A CN 1772300A CN 200510095001 A CN200510095001 A CN 200510095001A CN 1772300 A CN1772300 A CN 1772300A
- Authority
- CN
- China
- Prior art keywords
- cancer
- magnetic
- nano
- targeted drug
- powder
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 128
- 230000005291 magnetic effect Effects 0.000 title claims abstract description 78
- 238000000015 thermotherapy Methods 0.000 title claims abstract description 41
- 230000008685 targeting Effects 0.000 title claims description 25
- 102100022019 Pregnancy-specific beta-1-glycoprotein 2 Human genes 0.000 title description 2
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 105
- 229940079593 drug Drugs 0.000 claims abstract description 74
- 239000006247 magnetic powder Substances 0.000 claims abstract description 64
- 201000011510 cancer Diseases 0.000 claims abstract description 46
- 238000002347 injection Methods 0.000 claims abstract description 34
- 239000007924 injection Substances 0.000 claims abstract description 34
- 238000011282 treatment Methods 0.000 claims abstract description 34
- 230000008878 coupling Effects 0.000 claims abstract description 27
- 238000010168 coupling process Methods 0.000 claims abstract description 27
- 238000005859 coupling reaction Methods 0.000 claims abstract description 27
- 230000000694 effects Effects 0.000 claims abstract description 23
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 18
- 239000002245 particle Substances 0.000 claims abstract description 9
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims abstract description 9
- 239000002105 nanoparticle Substances 0.000 claims abstract description 8
- 231100000331 toxic Toxicity 0.000 claims abstract description 7
- 230000002588 toxic effect Effects 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 239000002552 dosage form Substances 0.000 claims abstract 2
- 230000002494 anti-cea effect Effects 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000000843 powder Substances 0.000 claims description 19
- 230000004048 modification Effects 0.000 claims description 13
- 238000012986 modification Methods 0.000 claims description 13
- 239000002994 raw material Substances 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 11
- 210000004369 blood Anatomy 0.000 claims description 9
- 239000008280 blood Substances 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 239000002773 nucleotide Substances 0.000 claims description 7
- 125000003729 nucleotide group Chemical group 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 239000004094 surface-active agent Substances 0.000 claims description 7
- 238000010353 genetic engineering Methods 0.000 claims description 6
- 239000002502 liposome Substances 0.000 claims description 6
- 239000012636 effector Substances 0.000 claims description 5
- 229910010272 inorganic material Inorganic materials 0.000 claims description 5
- 239000011147 inorganic material Substances 0.000 claims description 5
- 239000003607 modifier Substances 0.000 claims description 5
- 239000011368 organic material Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 229920001503 Glucan Polymers 0.000 claims description 4
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 4
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 4
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 3
- -1 enuatrol Chemical compound 0.000 claims description 3
- 230000005308 ferrimagnetism Effects 0.000 claims description 3
- 239000012155 injection solvent Substances 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- 230000005307 ferromagnetism Effects 0.000 claims description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 2
- 239000010931 gold Substances 0.000 claims description 2
- 229910052737 gold Inorganic materials 0.000 claims description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- 229920001610 polycaprolactone Polymers 0.000 claims description 2
- 239000004632 polycaprolactone Substances 0.000 claims description 2
- 239000004626 polylactic acid Substances 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 230000015556 catabolic process Effects 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 claims 1
- 239000008363 phosphate buffer Substances 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 abstract description 32
- 208000029742 colonic neoplasm Diseases 0.000 abstract description 31
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract description 27
- 206010006187 Breast cancer Diseases 0.000 abstract description 22
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 22
- 208000005718 Stomach Neoplasms Diseases 0.000 abstract description 22
- 206010017758 gastric cancer Diseases 0.000 abstract description 22
- 201000011549 stomach cancer Diseases 0.000 abstract description 22
- 206010061902 Pancreatic neoplasm Diseases 0.000 abstract description 21
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 abstract description 21
- 238000000034 method Methods 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 2
- 238000006065 biodegradation reaction Methods 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 206010020843 Hyperthermia Diseases 0.000 abstract 1
- 230000004071 biological effect Effects 0.000 abstract 1
- 230000036031 hyperthermia Effects 0.000 abstract 1
- 201000007270 liver cancer Diseases 0.000 abstract 1
- 208000014018 liver neoplasm Diseases 0.000 abstract 1
- 201000005202 lung cancer Diseases 0.000 abstract 1
- 208000020816 lung neoplasm Diseases 0.000 abstract 1
- 201000002528 pancreatic cancer Diseases 0.000 abstract 1
- 208000008443 pancreatic carcinoma Diseases 0.000 abstract 1
- 241000699660 Mus musculus Species 0.000 description 22
- 238000011580 nude mouse model Methods 0.000 description 22
- 201000008275 breast carcinoma Diseases 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 14
- 230000034994 death Effects 0.000 description 8
- 231100000957 no side effect Toxicity 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 240000002853 Nelumbo nucifera Species 0.000 description 3
- 235000006508 Nelumbo nucifera Nutrition 0.000 description 3
- 235000006510 Nelumbo pentapetala Nutrition 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000008676 import Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000003677 hemocyte Anatomy 0.000 description 2
- 229940000351 hemocyte Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 206010061188 Haematotoxicity Diseases 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000002149 energy-dispersive X-ray emission spectroscopy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 231100000226 haematotoxicity Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000000640 hydroxylating effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000696 magnetic material Substances 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及一种结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症磁热疗用纳米磁粉－抗CEA抗体靶向药物。其特征在于：将纳米磁粉与抗体通过溶液混合偶联制成磁热疗用纳米靶向药物，纳米磁粉与抗体的重量配比为1∶0.0001～0.20，靶向药物的颗粒粒径为5～1000nm，靶向药物的纳米磁粉表面偶联有抗体1个或多个抗体，具有生物活性；靶向药物的剂型为注射剂，在注射剂中药物分散为纳米颗粒；靶向药物通过注射主动靶向浓聚定位在癌症病灶；浓聚定位在癌症病灶的靶向药物在磁热疗治疗仪交变磁场的作用下产生磁滞生热效应，磁滞生热能力为10－7000W/gFe，加热癌症肿瘤至42－95℃，杀灭癌症肿瘤；靶向药物具有生物降解功能，用于癌症磁热疗治疗和预防没有毒副作用。
Description
技术领域
本发明涉及一种结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症磁热疗用纳米磁粉-抗CEA抗体靶向药物。
背景技术
癌症是对人类健康危害最大的疾病之一。我国每年新增癌症病人约220～250万，死亡人数分别列城市和农村居民死因的第一位和第二位。专家预测，今后二十年我国恶性肿瘤病人将增加一倍，人类面临着防治癌症的新的挑战。目前我国肺癌、肝癌、胃癌、食管癌、结直肠癌、乳腺癌、宫颈癌及鼻咽癌等合计占癌症死因的80％以上，是癌症防治的重点。近些年，由于具有高效、低毒、副作用小等特点抗体靶向药物的出现，抗体偶联放射核素、毒素、化疗药物以及抗体偶联前体药物等靶向药物已成为广泛研究应用的抗结肠癌、肝癌和肺癌等癌症的新型药物和结肠癌、肝癌和肺癌等癌症治疗的新手段，抗体靶向药物的应用为癌症的治疗和预防提供了新的机遇和效果。但上述靶向药物中抗体偶联的放射核素、毒素、化学药物以及前体药物等效应分子仍具有共同的缺陷，它们都具有较强的毒副作用，虽然靶向药物的毒性较未偶联抗体的核素、毒素或化疗药物明显降低，然而其应用对人体来说仍具有一定的非特异毒性，包括血液毒性和对正常组织的毒性，这使其在临床应用上仍有一定的局限性，结肠癌、肺癌等癌症治疗用抗体靶向药物的发展需要无毒副作用的新型效应分子。
肿瘤磁热疗是一种利用导入体内肿瘤病灶的磁热种子(即磁性颗粒或材料，如纳米磁粉)在体外交变磁场的作用下产生磁滞生热效应加热肿瘤、利用肿瘤细胞耐热性差选择性杀灭肿瘤细胞、无毒副作用、安全有效治疗肿瘤的热疗新方法。近几年，大量的研究成果表明应用磁热疗治疗恶性肿瘤不仅可以有效杀灭肿瘤，使肿瘤完全消退，并且没有毒副作用，磁热疗是一种具有广阔应用前景的肿瘤治疗新方法。磁热疗中的磁热种子实际上是一种无毒副作用物理效应分子。但迄今为止，磁热疗中磁热种子仍需通过埋植、局部注射、介导等方式导入肿瘤病灶，尚未见将纳米磁粉与抗体偶联制成磁热疗用将磁热种子(即纳米磁粉)主动靶向导入肿瘤病灶的靶向药物的文献报道。
发明内容
本发明的目的是针对上述不足之处提供一种磁热疗用纳米磁粉-抗CEA抗体靶向药物。由于磁热疗用纳米磁粉-抗CEA抗体靶向药物是以纳米磁粉为效应分子(即磁热疗用磁热种子)和以抗体为导向分子，由抗CEA抗体与纳米磁粉偶联构成的、具有抗CEA抗体对于结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症的靶向功能、纳米磁粉效应分子的磁热疗无毒副作用功能和纳米颗粒药物的穿透性，能够将纳米磁粉主动靶向导入癌症病灶的磁热疗用纳米靶向药物。它具有偶联抗体药物的主动靶向、载磁药物的磁性靶向及纳米载体药物的被动靶向等复合靶向功能和利用磁热疗治疗肿瘤的技术特征，它的应用可以通过动静脉或腹腔注射或导入等给药途径，使靶向药物主动靶向浓聚定位在与抗体具有较高特异性和亲和性的结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症病灶，实现结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症的无毒副作用的磁热疗治疗，为结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症的治疗和预防提供一种靶向磁热疗、高效杀灭、安全无毒副作用的新手段。
本发明是采取以下技术方案实现的：一种磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于(1)以具有磁滞生热能力的纳米磁粉为效应分子、以抗体为导向分子，将纳米磁粉与抗体通过溶液混合偶联制成具有主动靶向、磁性靶向和被动靶向功能的磁热疗用纳米靶向药物，纳米磁粉与抗体的重量配比为1∶0.0001～0.20，靶向药物的颗粒粒径为5～1000nm，靶向药物的纳米磁粉表面偶联有抗体1个或多个抗体并且偶联抗体具有生物活性；(2)靶向药物的应用需要制成复合溶媒或纯水的靶向药物注射剂，靶向药物制成注射剂使药物分散为纳米颗粒，具有良好的穿透性以及与相关的结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症细胞具有良好的特异性和亲和性，在体内外具有良好的导向作用，但和正常细胞无交叉反应；(3)靶向药物通过注射主动靶向高倍浓聚定位在与抗体具有较高特异性和亲和性的癌症病灶；(4)靶向药物在磁热疗治疗仪交变磁场的作用下使癌症病灶的纳米磁粉产生磁滞生热效应加热癌症肿瘤至42-95℃，进行高效杀灭、安全无毒副作用的靶向磁热疗治疗和预防，杀灭结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症肿瘤；(5)靶向药物具有生物降解性，药物应用剂量通常小于100mg，用于癌症磁热疗治疗和预防没有毒副作用。为了便于储存，靶向药物可以通过干燥制成可用于临用前配制注射剂的固体粉体。
所述的纳米磁粉为颗粒粒径1～5nm、5～10nm、10～20nm、20～40nm、30～50nm、50～100nm、1～100nm以及100～1000nm，纳米磁粉表面经过表面活性剂、表面改性剂改性、修饰或有机、无机物质包裹、包被或未经改性修饰和包裹包被的铁磁性、亚铁磁性和超顺磁性纳米磁粉。纳米磁粉表面经过1次或多次表面活性剂、表面改性剂改性、修饰或有机、无机物质包裹、包被的目的是使纳米磁粉具有不同功能化的表面，如阴离子化表面、阳离子化表面、非离子化表面、氨基化表面、巯基化表面、羟基化表面、羧基化表面、无机物表面、聚合物表面、生物表面以及其它能与抗体偶联的功能化表面。其中的表面活性剂和表面改性包括十二烷基硫酸钠、油酸钠、正癸酸、聚乙二醇、葡聚糖、核苷酸、多肽，纳米磁粉与表面活性剂或表面改性剂的原料重量比例为1∶0.0001～0.20。而有机物质包括脂质体、聚乳酸、聚己内酯、蛋白质；无机物质包括二氧化硅纳米颗粒、氧化铝纳米颗粒、金纳米颗粒，纳米磁粉与有机或无机物质的原料重量比例为1∶0.01～5.0。
所述的抗CEA抗体为抗CEA抗体及其Fab片段、基因工程抗体。抗CEA抗体对结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症具有良好的特异性和亲和性，而其Fab片段、基因工程抗体在免疫原性、穿透性以及各种水解酶的抵抗力方面都优于常规的单抗，如用酶切法制备的抗CEA抗体片段，分子量较小，比常规的单抗更易穿透到达肿瘤部位。
所述的通过溶液混合偶联为在水溶液、纯水或有机单质及其溶液中混合偶联。
所述的靶向药物在注射剂中为纳米颗粒是为了使靶向药物具有良好的穿透性，并且具有与相关癌细胞良好的特异性和亲和性。
所述的靶向药物通过注射主动靶向高倍浓聚定位为靶向药物主动靶向浓聚定位在癌症病灶的浓度是正常组织血液中药物浓度的1-1000倍。
所述的靶向药物在磁热疗治疗仪的交变磁场作用下的磁滞生热能力为10-7000W/gFe。
所述的靶向药物注射剂包括靶向药物偶联后制成的注射剂和临用前用靶向药物干燥固体粉体配制的注射剂。靶向药物制成干燥固体粉体有利于药物长期储存和性能保持稳定。
所述的复合溶媒或纯水的靶向药物注射剂为靶向药物分散在生理盐水、PBS、聚乙二醇、核苷酸等溶有无机、有机、生物、非生物物质的复合溶媒中或纯水中的制剂，其中靶向药物与复合溶媒或纯水的重量比例为1∶0.5～100，注射剂溶媒中纯水与无机或有机或生物或非生物物质的重量比例为1∶0～0.20。
本发明的靶向药物是由抗CEA抗体或其Fab片段或基因工程抗体与不同粒径的纳米磁粉偶联构成的纳米颗粒药物，由于药物实现了纳米化，其在体内具有良好的穿透性、生物相容性、在血液中具有长循环稳定性，使它不仅具有抗体导向的主动靶向功能，而且具有载磁药物的磁性靶向功能和利用肿瘤的EPR效应(enhanced permeabilityand retention effect)的纳米药物颗粒的被动靶向功能，是一种具有主动靶向功能和多种其它靶向功能的复合靶向药物。
本发明的靶向药物中基因工程抗体或CEA抗体片段等，其分子量较小，比常规的单抗更易穿透到达癌症病灶。采用基因工程抗体构成的磁热疗用纳米磁粉-抗CEA抗体靶向药物具有更好穿透功能和靶向功能。
本发明的靶向药物以纳米磁粉为磁热疗用磁热种子、抗体为导向分子，其中的纳米磁粉可以通过动静脉或腹腔注射或导入等给药途径，在抗体的导向等靶向功能作用下，实现药物主动靶向浓聚定位在结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症病灶，在磁热疗治疗仪交变磁场的作用下，患者病灶的纳米磁粉产生显著的磁滞生热效应，使癌症病灶迅速升温至42-95℃，对癌症进行42-48℃的磁热疗治疗，也可以进行高于48℃的磁热疗治疗。
本发明的磁热疗用靶向药物的应用通常可以通过1次1小时以及1小时以上的磁热疗有效杀灭结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症，甚至使肿瘤完全消退；也可以通过多次1小时以及1小时以上的磁热疗有效杀灭结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症，甚至使肿瘤完全消退。
本发明的靶向药物中纳米磁粉可以生物降解，通常治疗用药物剂量小于100mg，它的应用具有生物降解性和无毒副作用的特点。
本发明的靶向药物不仅可以用于结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症的靶向磁热疗治疗，而且可以用于结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症靶向磁热疗预防，即可以用于已经检测到的和未检测到的结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症肿瘤的主动靶向磁热疗治疗，仅有极小结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症肿瘤且影象设备无法检测到的早期结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症肿瘤的主动靶向磁热疗治疗，结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症仅有几个细胞时的早期肿瘤的主动靶向磁热疗治疗，结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症转移细胞和癌栓的主动靶向磁热疗杀灭治疗，以及正常人定期和不定期的结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症细胞主动靶向磁热疗杀灭的预防性治疗。
以下结合实施例对本发明作进一步的说明。
实施例1
将粒径分布范围为1～5nm、约10nm和10～40nm、30～50nm、50～100nm、100～150nm与950nm并分别经油酸钠、正癸酸、聚乙二醇等进行表面改性修饰或分别经葡聚糖、脂质体、纳米SiO2等进行包裹包被或未经表面修饰改性和包裹包被的超顺磁性和亚铁磁性纳米磁粉与抗CEA抗体分别以重量配比为1∶0.2、1∶0.1和1∶0.1、1∶0.05、1∶0.001、1∶0.0001在水溶液中混合偶联制得纳米磁粉-抗CEA抗体靶向药物。采用Zetasizer3000激光粒度分析仪测定表明，由粒径分布范围为1～5nm、约10nm和10～40nm、30～50nm、50～100nm、100～150nm与950nm的纳米磁粉制得的靶向药物粒径分布范围分别为15～20nm、约20nm和20～70nm、40～80nm、60～130nm、110～180nm与960～1000nm，其中纳米磁粉与油酸钠、正癸酸、聚乙二醇的原料重量投料比例分别为1∶0.0001、1∶0.05、1∶0.20，纳米磁粉与葡聚糖、脂质体、纳米SiO2的原料重量投料比例分别为1∶0.01、1∶0.1、1∶5.0，纳米磁粉的表面改性修饰和包裹包被对药物的颗粒粒径有不同程度的影响。
实施例2
经JEM-2010 UHR高分辨率透射电镜分析表明，上述实施例1中由颗粒粒径约10nm的超顺磁性纳米磁粉与抗CEA抗体偶联构成的靶向药物的颗粒粒径约为20nm，药物中纳米磁粉与抗体形成了良好的偶联，药物的纳米磁粉表面偶联着1个抗CEA抗体。
实施例3
(1)将原料重量比例为1∶0.005的纳米磁粉与油酸钠在水中混合后，再将原料重量比例为1∶0.005的纳米磁粉与十二烷基硫酸钠在水中混合制成纳米磁粉经过2次修饰改性的功能化表面。(2)将原料重量比例为1∶0.01的纳米磁粉与聚乙二醇在水中混合后，再将原料重量比例为1∶1.5的纳米磁粉与二氧化硅纳米颗粒在水中混合制成纳米磁粉经过1次改性和1次包裹的功能化表面。(3)将原料重量比例为1∶0.01的纳米磁粉与聚乙二醇在水中混合后，再将溶于乙醇的脂质体溶液与水中的聚乙二醇改性纳米磁粉混合制成经过1次改性和1次包被的功能化表面，其中纳米磁粉与脂质体的原料重量比例为1∶0.5。
实施例4
将上述实施例1中的靶向药物经浓度1％的PBS水溶液洗涤后再离心，除去上清，分别用纯水、浓度1％的PBS水溶液、核苷酸水溶液(其中注射剂溶媒中纯水与核苷酸的重量比例为1∶0.20)制成靶向药物与纯水、浓度1％的PBS水溶液、核苷酸水溶液的重量比例为1∶0.5、1∶10和1∶100的靶向药物注射剂。
实施例5
将上述实施例1中的靶向药物经浓度1％的生理盐水洗涤后再离心，除去上清，经冷冻干燥制成靶向药物固体粉体。
实施例6
(1)ELISA实验测得颗粒粒径为20～70nm的纳米磁粉-抗CEA抗体片段Fab靶向药物的免疫活性为63％。(2)体外稳定性实验表明，颗粒粒径为20～70nm的纳米磁粉-抗CEA抗体靶向药物注射液经37℃孵育24小时，无论在生理盐水中还是人血清白蛋白中，纳米磁粉脱落都小于5％，纳米磁粉-抗CEA抗体靶向药物在体外稳定。
实施例7
(1)将颗粒粒径为50～100nm的铁磁性纳米磁粉(其磁滞生热功率为10W/gFe)-抗CEA抗体靶向药物与结肠癌细胞LS174T混合，在超声功率为1～25W时经Zetasizer2000激光粒度分析仪检测，纳米磁粉-抗CEA抗体靶向药物与癌细胞以及纳米磁粉颗粒与抗体结合不脱落。(2)将颗粒粒径为50～100nm的纳米磁粉-抗CEA抗体靶向药物与结肠癌细胞LS174T、血细胞、正常肝细胞混合在一起，经磁分离后，仅结肠癌细胞LS174T在磁场下滞留，血细胞和正常肝细胞与结肠癌细胞LS174T完全分离。实验结果表明，纳米磁粉与抗CEA抗体具有较强的偶联结合力和稳定性，纳米磁粉-抗CEA抗体靶向药物与结肠癌细胞LS174T具有良好的靶向性和较强的亲和力，纳米磁粉-抗CEA抗体靶向药物与血液和肝脏等具有良好的生物相容性。
实施例8
将荷结肠癌细胞LS174T裸鼠尾静脉注射颗粒粒径为20～50nm的纳米磁粉(其磁滞生热功率为7000W/gFe)-抗CEA抗体靶向药物30mg后30分钟后处死，取肿瘤和心、脑、脾、肾、肠、肝等重要器官进行扫描电镜研究。电镜和能谱分析结果表明，注射靶向药物的裸鼠肿瘤毛细血管血液中和肿瘤组织中Fe元素(Fe元素是纳米磁粉的主要元素，约占纳米磁粉重量的70％。)占组织中Fe、Ca、Si、Al、Mg、K、Na、P、O、C等10种主要元素的重量比例分别从对照组(未注射靶向药物的)裸鼠肿瘤毛细血管血液中和肿瘤组织中的0.08％和0％提高到23.11％和0.83％，并且也高于注射靶向药物的裸鼠非肿瘤血管中的0.14％、正常肝脏组织中的0.14％和其它器官中的0.14％以下。靶向药物在裸鼠肿瘤毛细血管血液中和肿瘤组织中比对照组(未注射靶向药物的)裸鼠肿瘤毛细血管血液中和肿瘤组织中以及注射靶向药物的裸鼠非肿瘤血管血液中和正常肝组织中分别增高289倍和-(由于对照组肿瘤中测不到Fe，无法计算)以165倍和165倍，既靶向药物在肿瘤中的含药量至少高于其它部位165倍，纳米磁粉-抗CEA抗体靶向药物在体内具有显著的靶向性能，能使靶向药物靶向浓聚定位在肿瘤病灶，而在其他部位不聚集。
实施例9
取荷人肺癌A549裸鼠16只，测定并计算肿瘤体积后，按肿瘤体积随机分成两组，第一组为对照组，每只裸鼠肿瘤部位注射纯水0.3ml，第二组每只裸鼠腹腔注射含有30mg纳米磁粉(其磁滞生热功率为2000W/gFe)-抗CEA抗体靶向药物的注射剂0.3ml，将第二组裸鼠置入磁热疗治疗仪交变磁场下42-43℃治疗65分钟2次，治疗10天后处死上述裸鼠、分离肿瘤，称取肿瘤重量。结果表明，第一组瘤重1.97±0.53g，第二组瘤重0.79±0.37g，治疗组的抑瘤率为60％，P值小于0.01。
实施例10
取荷结肠癌细胞LS174T裸鼠16只，测定并计算肿瘤体积后，按肿瘤体积随机分成两组，第一组为对照组，每只裸鼠肿瘤部位注射纯水0.3ml，第二组每只裸鼠尾静脉注射含有50mg纳米磁粉(其磁滞生热功率为300W/gFe)-抗CEA抗体靶向药物的注射剂0.3ml，将第二组裸鼠置入磁热疗治疗仪交变磁场下42-43℃治疗1小时，治疗10天后处死上述裸鼠、分离肿瘤，称取肿瘤重量。结果表明，第一组瘤重2.97±0.65g，第二组瘤重0.12±0.31g，治疗组的抑瘤率为96％，P值小于0.01，并且其中2只裸鼠肿瘤完全消退，3只裸鼠肿瘤残余组织病理图片分析发现肿瘤细胞全部凝固性坏死，2只裸鼠肿瘤残余组织病理图片分析发现仅有少量未坏死肿瘤细胞。同时，在治疗后十天对第二组裸鼠进行体重和不良反应观测，未见明显异常，裸鼠处死后，取心、脑、脾、肾、肠、肝等重要器官做病理检查，未见明显异常。动物实验结果显示，采用纳米磁粉-抗CEA抗体靶向药物进行磁热疗可以实现靶向、高效、安全、无毒副作用杀灭肿瘤，甚至使肿瘤完全消退，纳米磁粉-抗CEA抗体靶向药在结肠癌、肺癌等多种癌症靶向治疗中有重要的应用价值。
值得指出的是，选用纳米磁粉-抗CEA抗体靶向药用于其它与抗体具有较高特异性和亲和性的结肠癌、胃癌、肝癌、肺癌、胰腺癌和乳腺癌等癌症的靶向磁热疗治疗和预防也可以取得同上的治疗和预防效果。
实施例11
取小白鼠和豚鼠各10只，在小白鼠和豚鼠腹腔分别注射0.5ml含0.3g和1.5ml含1.0g的纳米磁粉-抗CEA抗体靶向药物，观察7天和30天后未见不良反应和体重下降，处死后，取心、脑、脾、肾、肠、肝等重要器官切片做病理检查，未见明显异常。观察30天后处死后，取心、脑、脾、肾、肠、肝等重要器官做磁热疗治疗试验，未见发热出现。通常肿瘤磁热疗治疗仅需要20～100mg纳米磁粉-抗CEA抗体靶向药物，从上述初步毒副实验结果可知，本发明的纳米磁粉-抗CEA抗体靶向药物具有生物降解性和无毒副作用。
Claims (8)
1、一种磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于：(1)以具有磁滞生热能力的纳米磁粉为效应分子、以抗CEA抗体为导向分子，将纳米磁粉与抗体通过溶液混合偶联制成具有主动靶向、磁性靶向和被动靶向功能的磁热疗用纳米靶向药物，纳米磁粉与抗体的重量配比为1∶0.0001～0.20，靶向药物的颗粒粒径为5～1000nm，靶向药物的纳米磁粉表面偶联有抗体1个或多个抗体并且偶联抗体具有生物活性；(2)靶向药物的剂型为注射剂，在注射剂中药物分散为纳米颗粒，具有良好的穿透性以及与相关的癌症癌细胞具有良好的特异性和亲和性；(3)靶向药物通过注射主动靶向浓聚定位在与抗体具有较高特异性和亲和性的癌症病灶，靶向药物在癌症病灶的浓度达到正常组织血液中药物浓度的1-1000倍；(4)浓聚定位在癌症病灶的靶向药物在磁热疗治疗仪交变磁场的作用下产生磁滞生热效应，磁滞生热能力为10-7000W/gFe，加热癌症肿瘤至42-95℃，杀灭癌症肿瘤；(5)靶向药物具有生物降解功能，药物应用剂量通常小于100mg，用于癌症磁热疗治疗和预防没有毒副作用。
2、根据权利要求1所述的磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于所述的纳米磁粉为颗粒粒径1～5nm、5～10nm、10～20nm、20～40nm、30～50nm、50～100nm、1～100nm以及100～1000nm，纳米磁粉表面经过表面活性剂、表面改性剂改性、修饰或有机、无机物质包裹、包被或未经改性修饰和包裹包被的铁磁性、亚铁磁性和超顺磁性纳米磁粉。
3、根据权利要求1或2所述的磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于其中的表面活性剂和表面改性包括十二烷基硫酸钠、油酸钠、正癸酸、聚乙二醇、葡聚糖、核苷酸、多肽，纳米磁粉与表面活性剂或表面改性剂的原料重量比例为1∶0.0001～0.20。
4、根据权利要求1或2所述的磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于有机物质包括脂质体、聚乳酸、聚己内酯、蛋白质；无机物质包括二氧化硅纳米颗粒、氧化铝纳米颗粒、金纳米颗粒；纳米磁粉与有机或无机物质的原料重量比例为1∶0.01～5.0。
5、根据权利要求1所述的磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于所述的抗CEA抗体为抗CEA抗体及其Fab片段、基因工程抗体。
6、根据权利要求1所述的磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于所述的通过溶液混合偶联为在水溶液、纯水或有机单质及其溶液中混合偶联。
7、根据权利要求1所述的磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于所述的靶向药物注射剂包括靶向药物偶联后制成的注射剂和临用前用靶向药物干燥固体粉体配制的注射剂
8、根据权利要求1或7所述的磁热疗用纳米磁粉-抗CEA抗体靶向药物，其特征在于所述的复合溶媒或纯水的靶向药物注射剂为靶向药物分散在生理盐水、磷酸盐缓冲液(PBS)、聚乙二醇、核苷酸等溶有无机、有机、生物、非生物物质的复合溶媒中或纯水中的制剂，其中靶向药物与复合溶媒或纯水的重量比例为1∶0.5～100，注射剂溶媒中纯水与无机或有机或生物或非生物物质的重量比例为1∶0～0.20。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510095001XA CN100509059C (zh) | 2005-10-25 | 2005-10-25 | 磁热疗用纳米磁粉-抗cea抗体靶向药物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510095001XA CN100509059C (zh) | 2005-10-25 | 2005-10-25 | 磁热疗用纳米磁粉-抗cea抗体靶向药物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1772300A true CN1772300A (zh) | 2006-05-17 |
| CN100509059C CN100509059C (zh) | 2009-07-08 |
Family
ID=36759551
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB200510095001XA Expired - Fee Related CN100509059C (zh) | 2005-10-25 | 2005-10-25 | 磁热疗用纳米磁粉-抗cea抗体靶向药物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100509059C (zh) |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007048326A1 (fr) * | 2005-10-25 | 2007-05-03 | Hong Zhu | Médicament ciblé nanométrique pour magnéto-thermothérapie de tumeurs malignes |
| CN100558406C (zh) * | 2008-03-20 | 2009-11-11 | 同济大学 | 具有磁热效应的温敏性载药胶束、制备方法及其使用方法 |
| CN1951495B (zh) * | 2005-10-25 | 2010-12-01 | 朱宏 | 恶性肿瘤磁热疗用纳米靶向药物 |
| CN103816578A (zh) * | 2014-03-05 | 2014-05-28 | 广州一代医药科技有限公司 | 一种抗肿瘤磁性纳米粒子药物的靶向给药装置 |
| US8772030B2 (en) | 2003-07-31 | 2014-07-08 | Universita Degli Studi Di Roma “La Sapienza” | Cardiac stem cells and methods for isolation of same |
| US9249392B2 (en) | 2010-04-30 | 2016-02-02 | Cedars-Sinai Medical Center | Methods and compositions for maintaining genomic stability in cultured stem cells |
| CN106256347A (zh) * | 2015-06-22 | 2016-12-28 | 香港城市大学 | 纳米颗粒组合物用作标靶癌症干细胞和处理癌症的方法 |
| US9828603B2 (en) | 2012-08-13 | 2017-11-28 | Cedars Sinai Medical Center | Exosomes and micro-ribonucleic acids for tissue regeneration |
| US9845457B2 (en) | 2010-04-30 | 2017-12-19 | Cedars-Sinai Medical Center | Maintenance of genomic stability in cultured stem cells |
| US9884076B2 (en) | 2012-06-05 | 2018-02-06 | Capricor, Inc. | Optimized methods for generation of cardiac stem cells from cardiac tissue and their use in cardiac therapy |
| US11253551B2 (en) | 2016-01-11 | 2022-02-22 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of heart failure with preserved ejection fraction |
| US11351200B2 (en) | 2016-06-03 | 2022-06-07 | Cedars-Sinai Medical Center | CDC-derived exosomes for treatment of ventricular tachyarrythmias |
| US11357799B2 (en) | 2014-10-03 | 2022-06-14 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of muscular dystrophy |
| US11541078B2 (en) | 2016-09-20 | 2023-01-03 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and their extracellular vesicles to retard or reverse aging and age-related disorders |
| US11660355B2 (en) | 2017-12-20 | 2023-05-30 | Cedars-Sinai Medical Center | Engineered extracellular vesicles for enhanced tissue delivery |
| US11660317B2 (en) | 2004-11-08 | 2023-05-30 | The Johns Hopkins University | Compositions comprising cardiosphere-derived cells for use in cell therapy |
| US11759482B2 (en) | 2017-04-19 | 2023-09-19 | Cedars-Sinai Medical Center | Methods and compositions for treating skeletal muscular dystrophy |
-
2005
- 2005-10-25 CN CNB200510095001XA patent/CN100509059C/zh not_active Expired - Fee Related
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8772030B2 (en) | 2003-07-31 | 2014-07-08 | Universita Degli Studi Di Roma “La Sapienza” | Cardiac stem cells and methods for isolation of same |
| US8846396B2 (en) | 2003-07-31 | 2014-09-30 | Universita Degli Studi Di Roma “La Sapienza” | Methods for the isolation of cardiac stem cells |
| US11660317B2 (en) | 2004-11-08 | 2023-05-30 | The Johns Hopkins University | Compositions comprising cardiosphere-derived cells for use in cell therapy |
| WO2007048326A1 (fr) * | 2005-10-25 | 2007-05-03 | Hong Zhu | Médicament ciblé nanométrique pour magnéto-thermothérapie de tumeurs malignes |
| CN1951495B (zh) * | 2005-10-25 | 2010-12-01 | 朱宏 | 恶性肿瘤磁热疗用纳米靶向药物 |
| CN100558406C (zh) * | 2008-03-20 | 2009-11-11 | 同济大学 | 具有磁热效应的温敏性载药胶束、制备方法及其使用方法 |
| US9845457B2 (en) | 2010-04-30 | 2017-12-19 | Cedars-Sinai Medical Center | Maintenance of genomic stability in cultured stem cells |
| US9249392B2 (en) | 2010-04-30 | 2016-02-02 | Cedars-Sinai Medical Center | Methods and compositions for maintaining genomic stability in cultured stem cells |
| US9884076B2 (en) | 2012-06-05 | 2018-02-06 | Capricor, Inc. | Optimized methods for generation of cardiac stem cells from cardiac tissue and their use in cardiac therapy |
| US11220687B2 (en) | 2012-08-13 | 2022-01-11 | Cedars-Sinai Medical Center | Exosomes and micro-ribonucleic acids for tissue regeneration |
| US9828603B2 (en) | 2012-08-13 | 2017-11-28 | Cedars Sinai Medical Center | Exosomes and micro-ribonucleic acids for tissue regeneration |
| US10457942B2 (en) | 2012-08-13 | 2019-10-29 | Cedars-Sinai Medical Center | Exosomes and micro-ribonucleic acids for tissue regeneration |
| CN103816578B (zh) * | 2014-03-05 | 2016-04-27 | 广州一代医药科技有限公司 | 一种抗肿瘤磁性纳米粒子药物的靶向给药装置 |
| CN103816578A (zh) * | 2014-03-05 | 2014-05-28 | 广州一代医药科技有限公司 | 一种抗肿瘤磁性纳米粒子药物的靶向给药装置 |
| US11357799B2 (en) | 2014-10-03 | 2022-06-14 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of muscular dystrophy |
| CN106256347A (zh) * | 2015-06-22 | 2016-12-28 | 香港城市大学 | 纳米颗粒组合物用作标靶癌症干细胞和处理癌症的方法 |
| US11253551B2 (en) | 2016-01-11 | 2022-02-22 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of heart failure with preserved ejection fraction |
| US11872251B2 (en) | 2016-01-11 | 2024-01-16 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and exosomes secreted by such cells in the treatment of heart failure with preserved ejection fraction |
| US11351200B2 (en) | 2016-06-03 | 2022-06-07 | Cedars-Sinai Medical Center | CDC-derived exosomes for treatment of ventricular tachyarrythmias |
| US11541078B2 (en) | 2016-09-20 | 2023-01-03 | Cedars-Sinai Medical Center | Cardiosphere-derived cells and their extracellular vesicles to retard or reverse aging and age-related disorders |
| US11759482B2 (en) | 2017-04-19 | 2023-09-19 | Cedars-Sinai Medical Center | Methods and compositions for treating skeletal muscular dystrophy |
| US11660355B2 (en) | 2017-12-20 | 2023-05-30 | Cedars-Sinai Medical Center | Engineered extracellular vesicles for enhanced tissue delivery |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100509059C (zh) | 2009-07-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100509059C (zh) | 磁热疗用纳米磁粉-抗cea抗体靶向药物 | |
| CN100355454C (zh) | 磁热疗用纳米磁粉－抗人肝癌单抗HAb18靶向药物 | |
| CN1772303A (zh) | 恶性肿瘤磁热疗用纳米磁粉－抗体靶向药物 | |
| Huang et al. | Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer | |
| Zhao et al. | Nanotechnology for cancer therapy based on chemotherapy | |
| He et al. | LRP1-mediated pH-sensitive polymersomes facilitate combination therapy of glioblastoma in vitro and in vivo | |
| Yang et al. | Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo | |
| Lammers et al. | Image-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy | |
| Paciotti et al. | Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery | |
| Fatima et al. | Folic acid conjugated poly (amidoamine) dendrimer as a smart nanocarriers for tracing, imaging, and treating cancers over-expressing folate receptors | |
| CN104013599B (zh) | 一种肿瘤特异性靶向给药的药物载体及其应用 | |
| Yang et al. | Au-siRNA@ aptamer nanocages as a high-efficiency drug and gene delivery system for targeted lung cancer therapy | |
| He et al. | Design of multifunctional magnetic iron oxide nanoparticles/mitoxantrone-loaded liposomes for both magnetic resonance imaging and targeted cancer therapy | |
| Fan et al. | cRGD-conjugated Fe3O4@ PDA-DOX multifunctional nanocomposites for MRI and antitumor chemo-photothermal therapy | |
| Yang et al. | Pilot study of targeting magnetic carbon nanotubes to lymph nodes | |
| Im et al. | Helicobacter pylori-targeting multiligand photosensitizer for effective antibacterial endoscopic photodynamic therapy | |
| Ryan et al. | Progress in the delivery of nanoparticle constructs: towards clinical translation | |
| Shao et al. | A smart multifunctional nanoparticle for enhanced near-infrared image-guided photothermal therapy against gastric cancer | |
| Ming et al. | Smart manganese dioxide-based lanthanide nanoprobes for triple-negative breast cancer precise gene synergistic chemodynamic therapy | |
| Dong et al. | Multifunctionalized gold sub‐nanometer particles for sensitizing radiotherapy against glioblastoma | |
| Qiu et al. | Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation | |
| Wu et al. | PDA-based drug delivery nanosystems: a potential approach for glioma treatment | |
| Wang et al. | Bacterial magnetosomes loaded with doxorubicin and transferrin improve targeted therapy of hepatocellular carcinoma | |
| Sawant et al. | Cancer research and therapy: Where are we today | |
| Jia et al. | Multi-functional self-assembly nanoparticles originating from small molecule natural product for oral insulin delivery through modulating tight junctions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: NANJING WUSHENG NANO TECHNOLOGY CO., LTD. Free format text: FORMER OWNER: NANJING UNIVERSITY OF TECHNOLOGY Effective date: 20150303 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 210009 NANJING, JIANGSU PROVINCE TO: 210024 NANJING, JIANGSU PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20150303 Address after: 210024 block E, No. 177, Guangzhou Road, Jiangsu, Nanjing, China Patentee after: Nanjing Wu Sheng Nano Technology Co.,Ltd. Address before: 210009 Gulou District, Jiangsu, Nanjing new model road, No. 5 Patentee before: Nanjing Tech University |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090708 Termination date: 20211025 |