紫杉醇
癌症
药物输送
医学
癌细胞
PLGA公司
全身给药
药理学
转移
纳米载体
癌症研究
体内
药品
化学
体外
内科学
生物
生物化学
生物技术
有机化学
作者
Elisabete Fernandes,Dylan Ferreira,Andreia Peixoto,Rui Freitas,Marta Relvas-Santos,Carlos Palmeira,Gabriela Martins,Anabela Barros,Lúcio Lara Santos,Bruno Sarmento,José Alexandre Ferreira
标识
DOI:10.1016/j.ijpharm.2019.118646
摘要
Gastric cancer is the third leading cause of cancer-related death worldwide, with half of patients developing metastasis within 5 years after curative treatment. Moreover, many patients cannot tolerate or complete systemic treatment due severe side-effects, reducing their effectiveness. Thus, targeted therapeutics are warranted to improve treatment outcomes and reduce toxicity. Herein, poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with 5-fluorouracil (5-FU) and paclitaxel were surface-functionalized with a monoclonal antibody targeting sialyl-Lewis A (sLeA), a known glycan mediating hematogenous metastasis. Nanoparticles, ranging from 137 to 330 nm, enabled the controlled release of cytotoxic drugs at neutral and acid pH, supporting potential for intravenous and oral administration. Nanoencapsulation also reduced the initial toxicity of the drugs against gastric cells, suggesting it may constitute a safer administration vehicle. Furthermore, nanoparticle functionalization significantly enhanced targeting to sLeA cells in vitro and ex vivo (over 40% in comparison to non-targeted nanoparticles). In summary, a glycoengineered nano-vehicle was successfully developed to deliver 5-FU and paclitaxel therapeutic agents to metastatic gastric cancer cells. We anticipate that this may constitute an important milestone to establish improved targeted therapeutics against gastric cancer. Given the pancarcinomic nature of the sLeA antigen, the translation of this solution to other models may be also envisaged.
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