Terracciano Monica, Shahbazi Mohammad-Ali, Correia Alexandra, Rea Ilaria, Lamberti Annalisa, De Stefano Luca, Santos Hélder A
Institute for Microelectronics and Microsystems, National Research Council, Naples, 80131, Italy.
Nanoscale. 2015 Dec 21;7(47):20063-74. doi: 10.1039/c5nr05173h. Epub 2015 Nov 16.
Diatomite is a natural porous silica material of sedimentary origin. Due to its peculiar properties, it can be considered as a valid surrogate of synthetic porous silica for nano-based drug delivery. In this work, we exploit the potential of diatomite nanoparticles (DNPs) for drug delivery with the aim of developing a successful dual-biofunctionalization method by polyethylene glycol (PEG) coverage and cell-penetrating peptide (CPP) bioconjugation, to improve the physicochemical and biological properties of the particles, to enhance the intracellular uptake in cancer cells, and to increase the biocompatibility of 3-aminopropyltriethoxysilane (APT) modified-DNPs. DNPs-APT-PEG-CPP showed hemocompatibility for up to 200 μg mL(-1) after 48 h of incubation with erythrocytes, with a hemolysis value of only 1.3%. The cytotoxicity of the modified-DNPs with a concentration up to 200 μg mL(-1) and incubation with MCF-7 and MDA-MB-231 breast cancer cells for 24 h, demonstrated that PEGylation and CPP-bioconjugation can strongly reduce the cytotoxicity of DNPs-APT. The cellular uptake of the modified-DNPs was also evaluated using the above mentioned cancer cell lines, showing that the CPP-bioconjugation can considerably increase the DNP cellular uptake. Moreover, the dual surface modification of DNPs improved both the loading of a poorly water-soluble anticancer drug, sorafenib, with a loading degree up to 22 wt%, and also enhanced the drug release profiles in aqueous solutions. Overall, this work demonstrates that the biofunctionalization of DNPs is a promising platform for drug delivery applications in cancer therapy as a result of its enhanced stability, biocompatibility, cellular uptake, and drug release profiles.
硅藻土是一种沉积成因的天然多孔二氧化硅材料。由于其独特的性质，它可被视为用于纳米药物递送的合成多孔二氧化硅的有效替代物。在这项工作中，我们开发了一种成功的双功能化方法，通过聚乙二醇（PEG）包覆和细胞穿透肽（CPP）生物共轭来利用硅藻土纳米颗粒（DNP）进行药物递送，以改善颗粒的物理化学和生物学性质，增强癌细胞的细胞内摄取，并提高3-氨基丙基三乙氧基硅烷（APT）修饰的DNP的生物相容性。与红细胞孵育48小时后，DNP-APT-PEG-CPP在高达200μg mL(-1)的浓度下显示出血液相容性，溶血值仅为1.3%。浓度高达200μg mL(-1)的修饰DNP与MCF-7和MDA-MB-231乳腺癌细胞孵育24小时的细胞毒性表明，聚乙二醇化和CPP生物共轭可显著降低DNP-APT的细胞毒性。还使用上述癌细胞系评估了修饰DNP的细胞摄取，结果表明CPP生物共轭可显著增加DNP的细胞摄取。此外，DNP的双表面修饰既提高了难溶性抗癌药物索拉非尼的负载量，负载度高达22 wt%，又增强了其在水溶液中的药物释放曲线。总体而言，这项工作表明，DNP的生物功能化因其增强的稳定性、生物相容性、细胞摄取和药物释放曲线，是癌症治疗中药物递送应用的一个有前景的平台。
