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1.³¬Ö§»¯¾Û£¨°·-õ¥£©-¾ÛÈéËá-¶þרéµõ£Á×Ö¬õ£ÒÒ´¼°·£¨HPAE-co-PLA/DPPE£©poly[(amine-ester)-co-(D,L-lactide)]/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine
2.¾Û(¹È°±Ëá-co-ÈéËá)-Á×Ö¬õ£ÒÒ´¼°·½ÓÖ¦¾ÛºÏÎïÄÉÃ×Ò©ÎïÔØÌå
Poly ( glutamic acid -co- ) - phosphatidylethanolamine grafted polymer nano drug carriers
3.°ÐÏò  target
4.Éñ¾­½ºÖÊÁöGliomas
5.¶à¹¦ÄÜÄÉÃ×Á£×ÓMultifunctional Nanoparticles
6.Ö×Áö°ÐÏòTumor targeting
7.Á÷ʽϸ°ûÒÇFlow Cytometry
8.¹²¾Û½¹¼¤¹âɨÃèÏÔ΢¾µConfocal laser scanning microscopy
9.×Ïɼ´¼  paclitaxel

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yjy2430499: ½ð±Ò+200, ·­ÒëEPI+1, ¡ï¡ï¡ï¡ï¡ï×î¼Ñ´ð°¸, ÐÁ¿àÀ² лл 2015-03-28 20:31:13
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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.
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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 .
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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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