Engineering Multi-functional Nanomaterials to Treat Metastatic Cancer

工程多功能纳米材料治疗转移性癌症

• 批准号: EP/M008657/1
• 负责人: Wafa Al-Jamal
• 金额: $ 12.73万
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FM008657%2F1
• 关键词: Engineering; Multi; functional; Nanomaterials; Treat

Prostate cancer is the most common type of cancer and the second most common cause of death in men in the UK. Cancer metastasis (cancer cells spread outside the primary tumour) is the most serious complication of prostate cancer, with median patient survival of 12-18 months with current available chemotherapeutics. Chemotherapy is an approach which utilises anti-cancer drugs for killing tumour cells however it is associated with undesirable side effects due to its acting on normal healthy cells. Following systemic administration, cytotoxic drugs are eliminated rapidly from the blood stream which results in poor drug accumulation at metastatic cancer lesions. To overcome these shortcomings, drugs have been encapsulated into ultra-small objects called "nanocarriers". Liposomes are one example of these nanocarriers, made of natural lipid composition thus considered as the safest nanocarrier systems developed so far. Encapsulation of drugs into liposomes prolongs their residency time in the blood by decreasing their renal and hepatic clearance. In addition, drug-loaded nanocarriers will utilise the tumour leaky vasculature, known as enhanced permeation and retention (EPR) effect, to improve drug delivery to cancer cells. However, the poor release of the drug from such nanocarriers is considered the main challenge in cancer drug delivery. In this proposal we describe the development of targeted delivery systems that recognise prostate cancer cells, and efficiently release the encapsulated chemotherapeutics in response to an externally applied magnetic field. Such an approach aims to increase drug accumulation at the tumour tissues, and reduce undesirable systemic side effects. The targeting ligand was chosen to recognise only prostate cancer cells as this targeting moiety recognises specific proteins (called PSMA) only expressed on this cell type thus sparing healthy tissues. To overcome the poor release of the drug, temperature-sensitive liposomes (TSL) will be formulated so that they "break down" and release the drug only at temperatures higher than the body temperature (i.e.42C). The temperature-sensitive liposomes will be developed by incorporating magnetic iron oxide nanoparticles inside the liposomes besides the anticancer drug. The magnetic nanoparticles will heat when exposed to a "safe" alternating magnetic field so that the drug can be released from the TSL. At the same time the magnetic nanoparticles will act as "imaging agents" so their accumulation in the tumour will be visualized by Magnetic Resonance Imaging (MRI). This proposal aims to translate our innovative delivery system as a potential therapy for metastatic prostate cancer. It is anticipated that safer and more effective targeted nanocarriers will emerge to treat metastatic prostate cancer so that chemotherapy side effects are hugely reduced.

前列腺癌是英国男性最常见的癌症类型，也是第二大常见的死亡原因。癌症转移（癌细胞扩散在原发性肿瘤之外）是前列腺癌最严重的并发症，中位患者的存活率为12-18个月，当前可用的化学治疗剂。化学疗法是一种利用抗癌药物来杀死肿瘤细胞的方法，但是由于其对正常健康细胞的作用，它与不良的副作用有关。全身给药后，从血液中迅速消除了细胞毒性药物，这导致转移性癌症病变处的药物积累差。为了克服这些缺点，药物已封装在称为“纳米载体”的超小all物体中。脂质体是这些纳米载体的一个例子，由天然脂质组成制成，因此被认为是迄今为止最安全的纳米载体系统。将药物封装到脂质体中，通过减少肾脏和肝清除率，可以延长其在血液中的居住时间。此外，载有药物的纳米载体将利用肿瘤泄漏的脉管系统（称为增强的渗透和保留效应（EPR）效应）来改善药物对癌细胞的递送。但是，从这种纳米载体中释放该药物的不良释放被认为是癌症药物输送的主要挑战。在此提案中，我们描述了识别前列腺癌细胞的靶向输送系统的发展，并有效地释放了对外部应用磁场的响应封装的化学治疗剂。这种方法旨在增加药物在肿瘤组织上的积累，并减少不良的全身副作用。选择靶向配体仅识别前列腺癌细胞，因为该靶向部分识别仅在该细胞类型上表达的特定蛋白质（称为PSMA），从而避免了健康组织。为了克服药物的释放，将配制对温度敏感的脂质体（TSL），以便它们“分解”并仅在高于体温高的温度下释放该药物（即42C）。温度敏感的脂质体将通过在抗癌药物以外的脂质体内掺入磁氧化铁纳米颗粒来开发。当暴露于“安全”交替的磁场时，磁性纳米颗粒将加热，以便可以从TSL释放该药物。同时，磁性纳米颗粒将充当“成像剂”，因此它们在肿瘤中的积累将通过磁共振成像（MRI）可视化。该建议旨在将我们的创新输送系统转化为转移性前列腺癌的潜在疗法。可以预料，更安全，更有效的靶向纳米载体将出现以治疗前列腺癌，从而大大降低化学疗法的副作用。

项目成果

Dually Targeted Bioinspired Nanovesicle Delays Advanced Prostate Cancer Tumour Growth In Vivo.

• DOI: 10.1016/j.actbio.2021.07.021
• 发表时间: 2021-07
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Guanglong Ma;Maja Severic;Matthew Barker;Sara G T Pereira;Amalia Ruiz;Calvin C L Cheung;W. Al-Jamal

Microfluidic Production of Lysolipid-Containing Temperature-Sensitive Liposomes.

• DOI: 10.3791/60907
• 发表时间: 2020-03
• 期刊: Journal of visualized experiments : JoVE
• 作者: Calvin C L Cheung;Guanglong Ma;Amalia Ruiz;W. Al-Jamal

Magneto-Erythrocyte Membrane Vesicles' Superior T2 MRI Contrast Agents to Magneto-Liposomes

磁红细胞膜囊泡的 T2 MRI 造影剂优于磁脂质体

• DOI: 10.3390/magnetochemistry7040051
• 发表时间: 2021
• 期刊: Magnetochemistry
• 影响因子: 2.7
• 作者: Kostevšek N