Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups.
Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups.
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DOI：
10.2147/ijn.s33803
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发表时间：
2012
影响因子：
8
通讯作者：
Isidoro C
中科院分区：
文献类型：
--
作者：
Ekkapongpisit M;Giovia A;Follo C;Caputo G;Isidoro C
纳米粒子工程携带化疗药物和敏感的成像探针是有效的工具，早期检测癌细胞，同时监测抗癌治疗的细胞毒性作用。在这里，我们报告的影响的大小（10-30 nm与50 nm），材料的类型（介孔二氧化硅与聚苯乙烯），和表面电荷功能化（无，胺基，或羧基）的生物相容性，摄取，区室化，和细胞内滞留的荧光标记的纳米粒子在培养的人卵巢癌细胞。我们还研究了小窝在纳米颗粒摄取机制中的参与。我们发现，介孔二氧化硅纳米粒子进入通过小窝介导的内吞作用，并达到溶酶体;然而，虽然50 nm的纳米粒子永久驻留在这些细胞器内，10 nm的纳米粒子很快重新定位在细胞质中。裸10 nm介孔二氧化硅纳米粒子显示最高和50 nm羧基修饰的介孔二氧化硅纳米粒子的最低的摄取率，分别。聚苯乙烯纳米颗粒的摄取也发生通过小窝独立的途径，并受到血清的负面影响。30 nm羧基修饰的聚苯乙烯纳米颗粒不定位于溶酶体中并且没有毒性，而50 nm胺修饰的聚苯乙烯纳米颗粒在溶酶体内积累并最终导致细胞死亡。表达小窝蛋白-1的卵巢癌细胞更可能内吞这些纳米颗粒。这些数据突出了在选择最合适的靶向癌细胞的纳米治疗剂时，考虑纳米颗粒的物理化学特性（即，材料，尺寸和化学基团上的表面电荷）和细胞膜的生化组成的重要性。
Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10–30 nm versus 50 nm), type of material (mesoporous silica versus polystyrene), and surface charge functionalization (none, amine groups, or carboxyl groups) on biocompatibility, uptake, compartmentalization, and intracellular retention of fluorescently labeled nanoparticles in cultured human ovarian cancer cells. We also investigated the involvement of caveolae in the mechanism of uptake of nanoparticles. We found that mesoporous silica nanoparticles entered via caveolae-mediated endocytosis and reached the lysosomes; however, while the 50 nm nanoparticles permanently resided within these organelles, the 10 nm nanoparticles soon relocated in the cytoplasm. Naked 10 nm mesoporous silica nanoparticles showed the highest and 50 nm carboxyl-modified mesoporous silica nanoparticles the lowest uptake rates, respectively. Polystyrene nanoparticle uptake also occurred via a caveolae-independent pathway, and was negatively affected by serum. The 30 nm carboxyl-modified polystyrene nanoparticles did not localize in lysosomes and were not toxic, while the 50 nm amine-modified polystyrene nanoparticles accumulated within lysosomes and eventually caused cell death. Ovarian cancer cells expressing caveolin-1 were more likely to endocytose these nanoparticles. These data highlight the importance of considering both the physicochemical characteristics (ie, material, size and surface charge on chemical groups) of nanoparticles and the biochemical composition of the cell membrane when choosing the most suitable nanotheranostics for targeting cancer cells.