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ÖÁ×ðľ³æ (ÖøÃûдÊÖ)
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- ºì»¨: 60
- Ìû×Ó: 2484
- ÔÚÏß: 1793Сʱ
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- ×¢²á: 2013-07-22
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2Â¥2015-03-28 00:32:26
genhunter
ÖÁ×ðľ³æ (ÖøÃûдÊÖ)
- ·ÒëEPI: 387
- Ó¦Öú: 259 (´óѧÉú)
- ½ð±Ò: 9757.4
- É¢½ð: 10
- ºì»¨: 60
- Ìû×Ó: 2484
- ÔÚÏß: 1793Сʱ
- ³æºÅ: 2558361
- ×¢²á: 2013-07-22
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Ð¯ÔØ×Ïɼ´¼°ÐÏò¶à¹¦ÄÜÄÉÃ×Á£×ÓÖÎÁÆÄÔ½ºÖÊÁöµÄʵÑéÑо¿ Preparation,Characterization and in vitro Testing of Paclitaxol-Loaded Multifunctional Nanoparticles on Glioma Cells ÕªÒª£ºÄ¿µÄ£º±¾Ñо¿Ö¼ÔÚÖÆ±¸Ò»ÖÖÐÂÐÍÐ¯ÔØ×Ïɼ´¼£¨PTX£©¶à¹¦ÄÜÄÉÃ׿ÅÁ££¬²¢Ñо¿ÆäÌåÍâÊÍÒ©¼°Æä¿¹Ö×ÁöÌØÐÔ¡£Ì½ÌÖÆä¶ÔÄÔ½ºÖÊÁöϸ°ûÔöÖ³ÒÖÖÆµÄÏà¹Ø»úÖÆ,ΪÆäÔÚµr¾ÏµÍ³¶ñÐÔÖ×ÁöÖеÄÓ¦ÓÃÌṩÀíÂÛ»ù´¡ Abstract: Aims: the purpose of this work is to prepare new multifunctional nanoparticles carrying paclitaxol , characterize its drug release and anti-tumor properties, and explore the mechanisms of cell proliferation inhibitory activities towards glioma cells in vitro. The findings may provide a basis for developing new therapeutic agents for the treatment of malignancies in the central nerve systems. ·½·¨£ºÖƱ¸³¬Ö§»¯¾Û£¨°·-õ¥£©-¾ÛÈéËá-¶þרéµõ£Á×Ö¬õ£ÒÒ´¼°·£¨HPAE-co-PLA/DPPE£©ÄÉÃ×Ò©ÎïÔØÌ壬ͨ¹ýË«ÈéÒººÍÄÉÃ׳Áµí·¨½«¿¹Ö×ÁöÄ£ÐÍÒ©Îï×Ïɼ´¼£¨PTX£©·â×°µ½¹²¾ÛÎïµÄÄÉÃ׿ÅÁ£¡£Ñ¡ÓÃU251ϸ°ûºÍC6ϸ°û½øÐÐϸ°ûÅàÑø£¬Í¨¹ý¶Ô¼ÓÔØPTXµÄÄÉÃ×ϵͳҩÎïÊÍ·ÅÇúÏßµÄÑо¿£¬ÀûÓÃCCK-8·¨¼ì²â¼ÓÔØ×Ïɼ´¼ÄÉÃ×Á£µÄÌåÍâÖ×Áöϸ°û¶¾ÐÔÊÔÑ飬ÀûÓÃÁ÷ʽϸ°ûÒǼì²âÒ©ÎïÔÚÖ×Áöϸ°ûÄÚ»ýÀÛÇé¿ö£¬¹²¾Û½¹¼¤¹âɨÃèÏÔ΢¾µ£¨ CLSM £©¼à²â×°ÔØPTXµÄÄÉÃ׿ÅÁ£ÔÚÖ×Áöϸ°ûÄÚ·Ö²¼µÄÑо¿¡£ Methods: Hyperbranched poly[(amine ester)-co-(D,L-lactide)]/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (HAPE-co-PLA/DPPE) was synthesized, and used as building blocks for the preparartion of nanaoparticles. Paclitaxol, a model anti-cancer drug was loaded into nanoparticles using double emulsion and co-precipitation methods. The PTX-loaded nanoparticles were studied for its in vitro drug release properties. In vitro cytotoxicity were measured using U251 and C6 glioma cell lines by CCK-8 assays. Quantitative cellular uptake of these nanoparticles was assessed using Flow Cytometry. The intracelluar trafficking of these nanoparticles were monitored by confocal laser scanning microscopy. ½á¹û£ºÐÂÐÍÐ¯ÔØ×Ïɼ´¼£¨PTX£©¶à¹¦ÄÜÄÉÃ׿ÅÁ££¨³¬Ö§»¯¾Û£¨°·-õ¥£©-¾ÛÈéËá-¶þרéµõ£Á×Ö¬õ£ÒÒ´¼°·£¨HPAE-co-PLA/DPPE£©ÄÉÃ×Ò©ÎïÔØÌ壩֯±¸³É¹¦£¬Ð¯ÔØ×Ïɼ´¼£¨PTX£©¶à¹¦ÄÜÄÉÃ׿ÅÁ£¾ßÓÐÃ÷ÏÔµÄϸ°û´©Í¸ÌØÐÔ£¬³ÊÏÖ»ºÊÍÇÒpHÃô¸ÐµÄÌåÍâÒ©ÎïÊÍ·ÅÌØÕ÷£¬Ïà±È·Ç°ÐÏòÔØÒ©ÄÉÃ×½ºÊø£¬Ö×Áö°ÐÏòÐÞÊεÄÔØÒ©ÄÉÃ×½ºÊøÄܹ»¸üÓÐЧµÄÒÖÖÆÌåÍâÅàÑøµÄϸ°ûµÄÉú³¤£¬¸üѸËٵش©Í¸Ï¸°ûĤ²¢¸ü¶àµÄÔÚϸ°ûÄÚ»ýÀÛ¡£¿ÉÒÔÃ÷ÏÔÌá¸ßÒ©ÎïµÄ¿¹Ö×Áö»îÐÔ¡£ Results: New PTX-loaded multifunctional HPAE-co-PLA/DPPE nanoparticles were successfully prepared. These nanoparticles readily entered cells and demonstrated pH-sensitive and slow release properties. Compared with a control PTX-nanoparticle formulation that was not target-selective, the multifunctional nanoparticles with tumor targeting modification became rapidly across cell membrane barriers and accumulated inside cells, resulted in more efficient inhibition on cell growth and potent anti-tumor activity in vitro . ½áÂÛ£º³É¹¦ÖƱ¸ÐÂÐÍÐ¯ÔØ×Ïɼ´¼£¨PTX£©¶à¹¦ÄÜÄÉÃ׿ÅÁ££¬¶Ô°ÐÏòºÍ·Ç°ÐÏòÔØÒ©ÄÉÃ×Á£×Ó¿çĤÐÐΪµÄʾ×ÙʵÑéÏÔʾ£¬Á½ÖÖÔØÒ©½ºÊøÍ¨¹ý²»Í¬µÄÄÚÍÌ;¾¶½øÈëϸ°û£¬µ«×îÖÕ¾ù¾Û»ýÔÚÈÜøÌåÖС£×°ÔØ×Ïɼ´¼ÄÉÃ×Á£×Ó±íÏÖ³ö¶ÔpHÃô¸ÐÐÔ¼°ÓÐЧµÄʱ¼äÑÓ³Ùϸ°û¶¾ÐÔ¡£Òò´Ë£¬¸Ã¹²¾ÛÎïµÄÄÉÃ׿ÅÁ£±»Ö¤Ã÷ÊÇÓÃÓÚ¿¹Ö×ÁöµÄÒ©ÎïµÝË͵ĿÉÓÃÔØÌå£¬Ð¯ÔØPTXºóÓнÏÃ÷ÏԵĿ¹Ö×Áö×÷Óã¬ÖµµÃ½øÒ»²½½øÐÐÌåÄÚÑо¿¡£ Conclusion: We have successfully prepared new PTX-loaded multifunctional nanoparticles. Cellular uptake studies revealed that targeted and non-targeted nanoparticles entered cells via different endocytosis pathways, though ultimately, both ended up in lysosomal compartments. We demonstrated that nanoparticles prepared from HAPE-co-PLA/DPPE copolymers can be used as a carrier for anti-cancer agents. PTX-loaded multifunctional nanoparticles exhibited pH-sensitive , slow release properties that resulted in more potent cytotoxicity, which warrants further in vivo testings. ¹Ø¼ü´Ê: Éñ¾½ºÖÊÁö£»×Ïɼ´¼£»¶à¹¦ÄÜÄÉÃ×Á£×Ó£»°ÐÏò Key words: Gliomas, paclitaxol , multifunctional nanoparticles, target-specific |

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