科学家发现增强纳米药物靶向肿瘤细胞新策略

2019-07-29 佚名上海药物所

实体瘤中肿瘤基质细胞和细胞外基质组成异常复杂的瘤内递送屏障，严重阻碍了药物在肿瘤组织中的渗透及其靶向肿瘤细胞的递送。同时，瘤内肿瘤细胞分布呈高度异质性，即使制备了纳米制剂也难以突破上述递送屏障靶向肿瘤细胞，严重影响了其临床治疗效果。

实体瘤中肿瘤基质细胞和细胞外基质组成异常复杂的瘤内递送屏障，严重阻碍了药物在肿瘤组织中的渗透及其靶向肿瘤细胞的递送。同时，瘤内肿瘤细胞分布呈高度异质性，即使制备了纳米制剂也难以突破上述递送屏障靶向肿瘤细胞，严重影响了其临床治疗效果。

针对上述难题，中国科学院上海药物研究所研究员张志文、李亚平领导团队利用仿生脂蛋白系统，通过光热效应破坏肿瘤基质屏障，提高纳米药物靶向肿瘤细胞。这一新策略可显着抑制乳腺癌的复发和转移。

该研究设计构建了仿生脂蛋白载体分别包载光敏剂DiR（D-bLP）和化疗药物DM1（M-bLP）。研究发现，D-bLP经静脉注射4T1肿瘤小鼠后能够高效靶向渗透其体内肿瘤组织，但在瘤内被TAM、CAF等基质细胞截留，无法到达肿瘤细胞区域。经808nm光照后，D-bLP产生的光热效应能够杀伤肿瘤基质细胞，破坏细胞外基质，从而突破肿瘤基质递送屏障。在此基础上，显着提高了二次注射的M-bLP在肿瘤组织的蓄积和渗透，使其到达瘤内肿瘤细胞区域的分布提高27倍，显着抑制了乳腺癌的复发和转移，效果显着优于脂质体对照组。

该研究揭示了肿瘤基质屏障对纳米药物瘤内分布的影响，提出并证实了通过调节肿瘤基质靶向肿瘤细胞递送的思路，为克服瘤内基质屏障靶向肿瘤细胞的药物递送提供了有意义的探索。

7月25日，《自然-通讯》杂志在线发表了该研究成果。该研究得到了国家重大科学研究计划、国家自然科学基金、中科院战略性先导科技专项(A类)和中科院青年创新促进会等的资助。

原始出处：
Tao Tan, Haiyan Hu, Hong Wang, et al. Bioinspired lipoproteins-mediated photothermia remodels tumor stroma to improve cancer cell accessibility of second nanoparticles,Nature Communicationsvolume, Article number: 3322 (2019) Published: 25 July 2019

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2020-03-26 旅苦化文_208

#科学家发现#

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2020-03-03 12498bd5m16暂无昵称

#药物靶向#

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2020-01-02 DEXTER3139

#纳米药#

78 0
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2019-08-03 1468d3cdm57暂无昵称

希望尽快能走到临床

121 0
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2019-07-31 hmwwww

#肿瘤细胞#

96 0
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2019-07-31 xugc

#纳米药物#

107 0
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2019-07-31 12498568m52暂无昵称

#新策略#

61 0
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2019-07-30 txqjm

谢谢了，学习

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