Gold nanomaterials for combinatorial photochemotherapy and theranostics

用于组合光化学疗法和治疗诊断学的金纳米材料

• 批准号: EP/M014649/1
• 负责人: George Pasparakis
• 金额: $ 111.2万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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%2FM014649%2F1
• 关键词: Gold; nanomaterials; combinatorial; photochemotherapy; theranostics

Pancreatic cancer is the fourth most lethal cancer with disappointing prognosis profile; according to Cancer Research UK, about 19 patients in every 100 (19%) live for at least 1 year after they are diagnosed. Only about 4 out of every 100 people diagnosed (4%) live for at least 5 years, and only 3 out of every 100 (3%) live for at least 10 years. Around 8,000 patients are diagnosed with pancreatic cancer annually which is now the ninth most common cancer in the UK. At present, surgery is the preferred choice of treatment, however, in cases where operation is not possible, chemotherapy is followed by systemic drug administration. Gemcitabine is the front line drug for pancreatic cancer, with relatively moderate therapeutic performance; as a result physicians administer high gemcitabine doses to compensate for the poor drug potency which leads to unavoidable side effects including severe tiredness and breathlessness, anaemia, high risk of infection, and hair loss. In essence, current pancreatic cancer therapies have marginally improved the disease prognosis and have not addressed patient compliance issues. In the present approach, we propose radically new therapeutic protocols that combine lasers and nanoparticles (these are small sized materials with diameters thousands of times smaller than the thickness of a human hair) to direct drugs at the diseased sites of the body in a specific manner without damaging healthy tissue. By pointing the laser beam directly to the diseased tissue, it should be possible to treat pancreatic tumours by activating the nanoparticles to release the drugs only within tumor areas and not to surrounding healthy tissue. Our proposed approach will allow us not only to guide the nanoparticles at tumor sites, but also enable us to precisely control the trajectory of the drug molecules within individual cancer cells to ensure that they reach their molecular targets. In addition, the proposed nanoparticles will be equipped with molecular imaging tags to allow for real-time monitoring of the therapeutic outcome during therapy. We envision that in the future oncologists will be able to treat cancers in a dynamic manner by continually adjusting drug dosage during treatment by gaining constant feedback information on the tumours' response to therapy by simultaneous imaging of the diseased area during treatment. The proposed concept, if successful, will constitute a conceptually new therapeutic platform which will open up new avenues in personalised therapeutics where the treatment protocols are dynamically adjusted to maximize the therapeutic outcome.

胰腺癌是第四大致死性癌症，预后状况令人失望;根据英国癌症研究，每100例患者中约有19例（19%）在诊断后至少存活1年。每100名确诊患者中只有4人（4%）至少活了5年，每100人中只有3人（3%）至少活了10年。每年约有8，000名患者被诊断患有胰腺癌，这是目前英国第九大最常见的癌症。目前，手术是治疗的首选，然而，在手术不可能的情况下，化疗后全身给药。吉西他滨是胰腺癌的一线药物，具有相对中等的治疗性能;因此，医生给予高剂量的吉西他滨以补偿导致不可避免的副作用（包括严重疲劳和呼吸困难、贫血、感染高风险和脱发）的不良药效。本质上，目前的胰腺癌疗法已经略微改善了疾病预后，并且没有解决患者依从性问题。在目前的方法中，我们提出了全新的治疗方案，将联合收割机激光和纳米颗粒（这些是直径比人类头发厚度小数千倍的小尺寸材料）结合起来，以特定的方式将药物引导到身体的患病部位，而不会损害健康组织。通过将激光束直接指向患病组织，应该可以通过激活纳米颗粒来治疗胰腺肿瘤，从而仅在肿瘤区域内释放药物，而不是周围的健康组织。我们提出的方法不仅使我们能够在肿瘤部位引导纳米颗粒，而且还使我们能够精确控制药物分子在单个癌细胞内的轨迹，以确保它们到达其分子靶点。此外，拟议的纳米颗粒将配备分子成像标签，以允许在治疗期间实时监测治疗结果。我们设想，在未来的肿瘤学家将能够治疗癌症在治疗过程中不断调整药物剂量，通过获得不断反馈信息的肿瘤的治疗反应，同时成像的患病区域在治疗过程中的动态方式。所提出的概念，如果成功的话，将构成一个概念上新的治疗平台，这将开辟个性化治疗的新途径，其中动态调整治疗方案，以最大限度地提高治疗效果。

项目成果

Polymer coated gold nanoshells for combinational photochemotherapy of pancreatic cancer with gemcitabine.

• DOI: 10.1038/s41598-021-88909-x
• 发表时间: 2021-04-30
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Emamzadeh M;Pasparakis G
• 通讯作者: Pasparakis G

Photochemical Internalization Using Natural Anticancer Drugs, Antimetabolites, and Nanoformulations: A Systematic Study against Breast and Pancreatic Cancer Cell Lines

• DOI: 10.1021/acs.molpharmaceut.2c01012
• 发表时间: 2023-02-20
• 期刊: MOLECULAR PHARMACEUTICS
• 影响因子: 4.9
• 作者: Barnett, Christopher;Joubert, Fanny;Pasparakis, George
• 通讯作者: Pasparakis, George

Transiently malleable multi-healable hydrogel nanocomposites based on responsive boronic acid copolymers

• DOI: 10.1039/c7py01202k
• 发表时间: 2018-01-28
• 期刊: POLYMER CHEMISTRY
• 影响因子: 4.6
• 作者: Amaral, Aderito J. R.;Emamzadeh, Mina;Pasparakis, George
• 通讯作者: Pasparakis, George

Responsive polymers as cell surface modifiers and 3D healable microenvironments

作为细胞表面改性剂和 3D 可修复微环境的响应聚合物

• 发表时间: 2018
• 作者: Amaral R

Nanoparticle forming polyelectrolyte complexes derived from well-defined block copolymers

• DOI: 10.1016/j.eurpolymj.2023.111977
• 发表时间: 2023-03
• 期刊: European Polymer Journal
• 影响因子: 6
• 作者: Sara E. Bakhtiari;Fanny Joubert;G. Pasparakis;S. Brocchini;Gareth R. Williams