Targeted nanoparticles for high-dose intracellular delivery of antibiotics

许多可能构成军事威胁的病原体，例如那些用作生物战剂的病原体，由于其低感染剂量、高死亡率以及往往对抗生素治疗难治而存在问题。抗生素的包封可以通过促进靶向的、感染特异性的细胞内摄取和细菌清除来提高现有抗生素的疗效并减少抗生素耐药性。本博士的目标是开发抗体偶联抗生素负载纳米颗粒，用于靶向高剂量抗生素到细菌和感染部位。在攻读博士学位期间，学生将把细菌特异性抗体结合到聚合体上，我们之前已经证明这种抗体对泰国伯克霍尔德氏菌有效。他们将使用细胞内感染试验来验证细菌以这种方式靶向增加制剂效力的假设。同时，学生将开发拉曼光谱方法来量化感染和未感染细胞中的抗生素负载和细胞内分配和释放。该项目将在一个充满活力和竞争力的跨学科新兴研究领域培养一名博士生，重点是翻译。它将涉及与共同资助该学生的外部组织（Dstl）密切合作。

Many pathogens that may present a military threat, such as those that be used as biowarfare agents, are problematic due to their low infectious dose, high mortality rate, and because they are often refractory to antibiotic treatment. Encapsulation of antibiotics may increase the efficacy of existing antibiotics and reduce antibiotic resistance by promoting targeted, infection-specific intracellular uptake and bacterial clearance. The aim of this PhD is to develop antibody-conjugated antibiotic-loaded nanoparticles for targeting high doses of antibiotics to bacteria and sites of infections. During the PhD, the student will conjugate bacteria-specific antibodies to polymersomes that we have previously shown to be effective against Burkholderia thailandensis. They will test the hypothesis that bacteria targeting in this manner increases the potency of the formulation using intracellular infection assays. In parallel, the student will develop methods in Raman spectroscopy to quantify antibiotic loading and intracellular partitioning and release in infected and uninfected cells. The project will lead to the training of a PhD student in a vibrant, competitive group in an in-terdisciplinary area of emerging research with a direct translation focus. It will involve close partnership with an external organisation who are co-funding this studentship (Dstl) .