Fonseca Leandro C, de Sousa Marcelo, Maia Djalma L S, Visani de Luna Luis, Alves Oswaldo L
Laboratory of Solid State Chemistry, Institute of Chemistry, Universidade Estadual de Campinas 13083-970 Campinas São Paulo Brazil
Nanoscale Adv. 2020 Feb 5;2(3):1290-1300. doi: 10.1039/c9na00752k. eCollection 2020 Mar 17.
Camptothecin (CPT) is a potent antitumor drug frequently used in studies of drug delivery systems. The poor water solubility and unfavourable pharmacokinetic conditions of CPT and the development of nanomaterials such as mesoporous silica nanoparticles (MSNs), graphene oxide (GO) and a new family of GO decorated with MSNs (GO-MSNs) motivated the present work, which sought to solve these challenges. In this context, release assays showed rapid and prolonged release, respectively, by silica and GO/GO-MSN nanomaterials; release was faster at pH 7.4 and slower at pH 5.0 in all situations. In particular, GO-MSNs presented an important advantage compared to GO due to their slower drug release at pH 7.4 (physiological conditions in blood; slowest release is expected under these conditions) and faster drug delivery at pH 5.0 (acidic conditions in endosomes of cancer cells; fastest release is expected under these conditions). The results, therefore, present the GO-MSN nanomaterial as a potential candidate for antitumor applications. The main drug-nanocarrier chemical interactions (London forces, hydrogen bonds, and electrostatic and dipole-dipole interactions) are also exhaustively described in order to understand the observed differences in drug delivery properties among these nanomaterials and to comprehend the influence of pH on concomitant and dynamic interactions.
喜树碱(CPT)是一种强效抗肿瘤药物,常用于药物递送系统的研究。CPT的水溶性差和药代动力学条件不佳,以及介孔二氧化硅纳米颗粒(MSNs)、氧化石墨烯(GO)和一种新型的MSN修饰的GO(GO-MSNs)等纳米材料的发展推动了本研究工作,旨在解决这些挑战。在此背景下,释放试验表明,二氧化硅和GO/GO-MSN纳米材料分别呈现快速和持续释放;在所有情况下,pH 7.4时释放更快,pH 5.0时释放更慢。特别是,与GO相比,GO-MSNs具有重要优势,因为它们在pH 7.4(血液中的生理条件;预计在这些条件下释放最慢)时药物释放较慢,而在pH 5.0(癌细胞内体中的酸性条件;预计在这些条件下释放最快)时药物递送更快。因此,结果表明GO-MSN纳米材料是抗肿瘤应用的潜在候选者。为了理解这些纳米材料之间观察到的药物递送特性差异以及理解pH对伴随和动态相互作用的影响,还详尽描述了主要的药物-纳米载体化学相互作用(伦敦力、氢键以及静电和偶极-偶极相互作用)。