NER: Neovasculature-Targeted Biogenic Magnetic Nanoparticles

0508535 Peng该提案是响应纳米科学与工程倡议，NSF 04-043，类别NER而收到的。在该拟议项目中，将研究功能化生物源磁性纳米颗粒靶向递送至携带avB 3整合素的肿瘤细胞，随后进行热疗治疗。由于磁性纳米颗粒可以被外部交变电磁场激发并用作热疗剂，因此通过avB 3整联蛋白将磁性纳米颗粒靶向内皮细胞可以提供一种有效的手段，通过有毒量的热能破坏新血管的生长，从而导致恶性细胞破坏。此外，根据已发表的报道，治疗性纳米颗粒在血流中的循环半衰期缩短（被单核吞噬细胞系统摄入）会阻止足够的纳米颗粒到达靶细胞。为了减轻纳米颗粒的吞噬作用，申请人提出将“自身标记物”整合素相关蛋白（CD 47）掺入从趋磁细菌提取的生物源磁性纳米颗粒的表面上。除了其抗吞噬功能外，与磁性纳米颗粒缀合的CD 47蛋白将作为靶向avB 3-整联蛋白表达细胞的配体。总之，预期所提出的CD 47缀合的磁性纳米颗粒在血液循环中具有更长的半衰期，因此允许通过整合素avB 3更有效的位点结合，并通过用电磁能激发位点靶向的磁性纳米颗粒来诱导肿瘤新生血管的热破坏。

0508535PengThis proposal was received in response to Nanoscale Science and Engineering initiative, NSF 04-043, category NER.In this proposed project, targeted delivery of functionalized biogenic magnetic nanoparticles to avB3 integrin-bearing tumor cells followed by hyperthermia treatment will be studied. Since magnetic nanoparticles can be excited by external alternating electromagnetic field and used as hyperthermia agents, targeting magnetic nanoparticles to endothelial cells via avB3 integrin may provide an effective means to disrupt the growth of new blood vessels by toxic amounts of thermal energy and thereby lead to malignant cell destruction. In addition, according to published accounts, shortened circulatory half-lives of therapeutic nanoparticles in the bloodstream (ingested by mononuclear phagocyte system) prevent sufficient nanoparticles from reaching the target cells. To mitigate phagocytosis of nanoparticles, the applicantproposes to incorporate the "marker of self" integrin-assocaited protein (CD47) on the surface of biogenic magnetic nanoparticles extracted from magnetotactic bacteria. In addition to its antiphagocytic feature, CD47 protein conjugated with magnetic nanoparticles will act as a ligand targeted for avB3-integrin expressing cells. In summary, the proposed CD47-conjugated magnetic nanoaprticles are expected to have much extended half-lives in blood circulation, hence allowing for more efficient site binding via integrin avB3 and inducing thermal destruction of tumor neovasculature by exciting site-targeted magnetic nanoparticles with electromagnetic energy.