Colin de Verdière A, Dubernet C, Nemati F, Poupon M F, Puisieux F, Couvreur P
Laboratoire de Pharmacie Galénique et Biopharmacie, URA CNRS 1218, Université de Paris-Sud, Chatenay Malabry, France.
Cancer Chemother Pharmacol. 1994;33(6):504-8. doi: 10.1007/BF00686509.
Previous studies have clearly demonstrated that polyisobutylcyanoacrylate (PIBCA) doxorubicin-loaded nanoparticles (NS-Dox PIBCA) can overcome the resistance of P388/ADR cells. In the present paper, we found that overcoming multidrug resistance with the aid of doxorubicin (Dox) loaded onto these nanoparticles was associated with an increased intracellular drug content. Indeed, after a 6-h incubation period, the amount of cell-associated drug was 5 times higher when the cells were incubated with NS-Dox PIBCA as compared with free Dox. Further experiments, such as uptake studies in the presence of cytochalasin B or efflux studies, indicated a possible mechanism of nanoparticle/cell interaction. These results suggested that nanoparticles did not enter the cells by an endocytic process, in contrast to a previous hypothesis.
先前的研究已清楚表明，聚异丁基氰基丙烯酸酯（PIBCA）负载阿霉素的纳米颗粒（NS-Dox PIBCA）能够克服P388/ADR细胞的耐药性。在本论文中，我们发现借助负载于这些纳米颗粒上的阿霉素（Dox）克服多药耐药性与细胞内药物含量增加有关。事实上，经过6小时的孵育期后，与游离阿霉素相比，当细胞与NS-Dox PIBCA一起孵育时，细胞相关药物的量高出5倍。进一步的实验，如在细胞松弛素B存在下的摄取研究或外排研究，表明了纳米颗粒/细胞相互作用的一种可能机制。这些结果表明，与先前的假设相反，纳米颗粒并非通过内吞过程进入细胞。
