Singlet Oxygen Degradable Materials to Harness the Near-Infrared Biological Transparency Window Efficiently

单线态氧可降解材料有效利用近红外生物透明窗口

• 批准号: 9214343
• 负责人: SAMUEL W THOMAS
• 金额: $ 18.5万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9214343
• 关键词: Address; Adverse effects; Area; Biological; Crosslinker; Development; Doxorubicin; Drug Delivery Systems; FDA approved; Future; Gel; Goals; Health; Heating; Human; Hydrogels; Laboratories; Light; Literature; Location; Longitudinal Studies; NanoGel; Outcome; Penetration; Pharmaceutical Preparations; Photosensitization; Polymers; Process; Reaction; Reactive Oxygen Species; Research; Series; Singlet Oxygen; Source; Testing; Therapeutic; Time; Tissues; Work; absorption; alternative treatment; base; cost; improved; innovation; irradiation; nanomedicine; nanoparticle; novel strategies; public health relevance; transmission process; two-photon

 DESCRIPTION: The use of light to trigger a highly localized release of drugs is promising but with the exception of treatment of tissues that can be irradiated with light directly, photo-triggered drug release is hindered by the extremely limited transmission through tissues of wavelengths outside of the "near-infrared window", between approximately 650 - 1300 nm. Photolabile moieties that absorb light efficiently in this window are nearly non-existent, and state-of-the-art approaches to access this window for triggered delivery, such as photothermal heating of nanoparticles or two-photon absorption of photocleavable linkers, use light inefficiently and therefore have highly limited effective penetration depths, even with powerful light sources. Our long-term goal is to develop photolabile triggered-release material platforms that are useful for the on- demand release of drugs. The objective of this application is to develop a new materials approach to phototriggered guest delivery that uses tissue-penetrant light to release trapped guests. Our central hypothesis, based on both previous works in our laboratory and literature precedent, is that hydrogels with alkoxyacene-based cross linkers will decompose upon photosensitization of singlet oxygen (1O2) with wavelengths greater than 650 nm, and that nanoparticles of these materials will enable efficient light- induced release of guests. The rationale of this project is that such materials will harness an efficient, red light-driven photophysical process that is already FDA-approved-1O2 photosensitization-to cause photoinduced release of therapeutics. Prof. Samuel Thomas is a recognized expert in the two areas where this application intersect-i) photolabile polymeric materials and ii) the reactions of photogenerated 1O2 with acenes, while Prof. Qiaobing Xu is an expert in nanomedicine and drug delivery. We will test our central hypothesis and accomplish our objective by pursuing the following Specific Aims: 1. Degrade macroscopic hydrogels with cross linkers containing alkoxylated acenes induced by 1O2 photogenerated with wavelengths ≥ 650 nm; 2. Release the drug doxorubicin from 1O2-labile nanogels. This application is innovative, as it is circumvents the inefficiencies inherent to current approaches to accessing the biological NIR window. We expect that our approach will yield the following outcomes: i) new material platforms that decompose on demand upon photogeneration of 1O2, ii) a series of acene-based moieties that span a broad range of reactivity in 1O2-induced bond cleavage, and iii) nanoparticles that release cargo into free solution upon irradiation with tissue-penetrant red or near-infrared light. This study, along with subsequent long-term studies, will have an important positive impact by increasing the efficacy of photo-induced therapeutic delivery, which will mitigate both off-target effects of the delivered drugs through spatial and temporal control, as well as side effects of irradiation itself. The proposed research is significant because it will enable spatially-selective triggered drug release deeper into tissues than is currently achievable.

 描述：利用光引发药物的高度局部化释放是有希望的，但除了可以直接用光照射的组织的治疗外，光触发的药物释放由于在近红外窗口之外的组织中的透射率极其有限而受到阻碍，大约在650-1300 nm之间。在这个窗口中有效吸收光的不发光部分几乎不存在，并且最先进的访问该窗口以进行触发传递的方法，例如纳米颗粒的光热加热或可光裂解连接体的双光子吸收，对光的利用效率低下，因此即使在强大的光源下，有效穿透深度也非常有限。我们的长期目标是开发可用于药物按需释放的耐光性触发释放材料平台。这项应用的目标是开发一种新的材料方法来光触发的客人递送，使用组织穿透光释放被困的客人。我们的中心假设是，基于我们实验室以前的工作和文献先例，基于烷氧基并苯的交联剂的水凝胶将在波长大于650 nm的单线态氧(1O2)的光敏化时分解，并且这些材料的纳米颗粒将能够有效地光诱导释放客体。这个项目的基本原理是，这种材料将利用一种高效的、红光驱动的光物理过程，该过程已经得到FDA的批准-102光敏化-以导致光诱导的治疗药物释放。Samuel Thomas教授是这项应用交叉的两个领域的公认专家-i)光敏聚合物材料和ii)光生1O2与苯类的反应，而徐巧冰教授是纳米医学和药物输送方面的专家。我们将验证我们的中心假设，并通过追求以下具体目标来实现我们的目标：1.降解由波长为≥650 nm的1O2光产生的含有烷氧基苯的交联剂的宏观水凝胶；2.从1O2-不稳定的纳米凝胶中释放药物阿霉素。这一应用是创新的，因为它绕过了目前访问生物近红外窗口的方法固有的低效。我们预计我们的方法将产生以下结果：i)新的材料平台，可在光生1O2时按需分解；ii)一系列基于并烯的部分，在1O2诱导的键断裂中具有广泛的反应活性；iii)纳米颗粒，在组织穿透性红色或近红外光照射下，将货物释放到自由溶液中。 这项研究以及随后的长期研究将产生重要的积极影响，提高光诱导治疗递送的有效性，这将通过空间和时间控制减轻递送药物的非靶向效应，以及辐射本身的副作用。拟议的研究具有重要意义，因为它将使空间选择性 引发药物释放到比目前可以达到的更深的组织中。

项目成果

UV and NIR-Responsive Layer-by-Layer Films Containing 6-Bromo-7-hydroxycoumarin Photolabile Groups.

• DOI: 10.1021/acs.langmuir.7b01469
• 发表时间: 2017-10-17
• 期刊: Langmuir : the ACS journal of surfaces and colloids
• 作者: Feeney MJ;Hu X;Srinivasan R;Van N;Hunter M;Georgakoudi I;Thomas SW 3rd
• 通讯作者: Thomas SW 3rd

Triggered Release of Encapsulated Cargo from Photoresponsive Polyelectrolyte Nanocomplexes.

光响应聚电解质纳米复合物中封装物质的触发释放。

• DOI: 10.1021/acsami.6b07366
• 发表时间: 2016
• 期刊: ACS applied materials & interfaces
• 影响因子: 9.5
• 作者: Hu,Xiaoran;Feeney,MatthewJ;McIntosh,Ethan;Mullahoo,James;Jia,Feng;Xu,Qiaobing;Thomas3rd,SamuelW
• 通讯作者: Thomas3rd,SamuelW