Rodríguez-Nogales Carlos, Moreno Haritz, Zandueta Carolina, Desmaële Didier, Lecanda Fernando, Couvreur Patrick, Blanco-Prieto María J
Chemistry and Pharmaceutical Technology Department, School of Pharmacy and Nutrition, Universidad de Navarra, 31008 Pamplona, Spain.
IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
Cancers (Basel). 2020 Jul 14;12(7):1895. doi: 10.3390/cancers12071895.
Due to chemoresistance and a high propensity to form lung metastasis, survival rates in pediatric osteosarcoma (OS) are poor. With the aim to improve anticancer activity in pediatric OS, a multidrug nanomedicine was designed using the alkyl-lysophospholipid edelfosine (EF) co-assembled with squalenoyl-gemcitabine (SQ-Gem) to form nanoassemblies (NAs) of 50 nm. SQ-Gem/EF NAs modified the total Gem pool exposure in the blood stream in comparison with SQ-Gem NAs, which correlated with a better tolerability and a lower toxicity profile after multiple intravenous administrations in mice. For in vivo preclinical assessment in an orthotopic OS tumor model, P1.15 OS cells were intratibially injected in athymic nude mice. SQ-Gem/EF NAs considerably decreased the primary tumor growth kinetics and reduced the number of lung metastases. Our findings support the candidature of this anticancer nanomedicine as a potential pediatric OS therapy.
由于化疗耐药性以及形成肺转移的高倾向，小儿骨肉瘤（OS）的生存率很低。为了提高小儿骨肉瘤的抗癌活性，设计了一种多药纳米药物，使用与角鲨烯基吉西他滨（SQ-Gem）共组装的烷基溶血磷脂依地福新（EF）形成50纳米的纳米组装体（NAs）。与SQ-Gem NAs相比，SQ-Gem/EF NAs改变了血流中吉西他滨总量的暴露情况，这与多次静脉注射小鼠后更好的耐受性和更低的毒性特征相关。为了在原位骨肉瘤肿瘤模型中进行体内临床前评估，将P1.15骨肉瘤细胞经胫骨内注射到无胸腺裸鼠体内。SQ-Gem/EF NAs显著降低了原发性肿瘤的生长动力学，并减少了肺转移的数量。我们的研究结果支持这种抗癌纳米药物作为小儿骨肉瘤潜在治疗方法的候选资格。
