...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Bioconjugate Chemistry >Hypoxia Responsive, Tumor Penetrating Lipid Nanoparticles for Delivery of Chemotherapeutics to Pancreatic Cancer Cell Spheroids
【24h】

Hypoxia Responsive, Tumor Penetrating Lipid Nanoparticles for Delivery of Chemotherapeutics to Pancreatic Cancer Cell Spheroids

机译：缺氧反应性，肿瘤穿透脂质纳米颗粒的化学疗法传递给胰腺癌细胞球体。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Solid tumors are often poorly irrigated due to structurally compromised microcirculation. Uncontrolled multiplication of cancer cells, insufficient blood flow, and the lack of enough oxygen and nutrients lead to the development of hypoxic regions in the tumor tissues. As the partial pressure of oxygen drops below the necessary level (10 psi), the cancer cells modulate their genetic makeup to survive. Hypoxia triggers tumor progression by enhancing angiogenesis, cancer stem cell production, remodeling of the extracellular matrix, and epigenetic changes in the cancer cells. However, the hypoxic regions are usually located deep in the tumors and are usually inaccessible to the intravenously injected drug carrier or the drug. Considering the designs of the reported nanoparticles, it is likely that the drug is delivered to the peripheral tumor tissues, close to the blood vessels. In this study, we prepared lipid nanoparticles (LNs) comprising the synthesized hypoxia-responsive lipid and a peptide lipid conjugate. We observed that the resultant LNs penetrated to the hypoxic regions of the tumors. Under low oxygen partial pressure, the hypoxia-responsive lipid undergoes reduction, destabilizing the lipid membrane, and releasing encapsulated drugs from the nanoparticles. We demonstrated the results employing spheroidal cultures of the pancreatic cancer cells BxPC-3. We observed that the peptide-decorated, drug encapsulated LNs reduced the viability of pancreatic cancer cells of the spheroids to 35% under hypoxic conditions.
机译：由于结构性微循环受损，实体瘤的灌注通常较差。癌细胞不受控制的繁殖，血液流动不足以及氧气和营养物质不足会导致肿瘤组织缺氧区域的发展。当氧气的分压降至必要水平（10 psi）以下时，癌细胞会调节其遗传组成以存活。缺氧通过增强血管生成，癌症干细胞的产生，细胞外基质的重塑以及癌细胞的表观遗传变化来触发肿瘤进展。但是，低氧区域通常位于肿瘤的深处，并且通常不能通过静脉注射的药物载体或药物进入。考虑到所报道的纳米颗粒的设计，药物很可能被递送到靠近血管的周围肿瘤组织。在这项研究中，我们制备了脂质纳米颗粒（LNs），包含合成的缺氧反应性脂质和肽脂质缀合物。我们观察到，由此产生的LNs渗透到肿瘤的低氧区域。在低氧分压下，对缺氧反应的脂质进行还原，使脂质膜不稳定，并从纳米颗粒中释放封装的药物。我们证明了采用胰腺癌细胞BxPC-3的球状培养的结果。我们观察到，在缺氧条件下，用肽修饰的药物包裹的LN会将球状体的胰腺癌细胞的存活率降低至35％。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号