Creating Safe Biodegradable Photoluminescent Implant Polymers

创造安全的可生物降解的光致发光植入聚合物

• 批准号: 8182724
• 负责人: Jian Yang
• 金额: $ 31.22万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-11 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8182724
• 关键词: Absorbable Implants; Address; Animals; Area; Biocompatible Materials; Biological; Biological Process; Biological Sciences; Biology; Biosensing Techniques; Cell-Mediated Cytolysis; Cells; Clinical; Custom; Development; Devices; Disease; Drug Delivery Systems; Dyes; Economics; Encapsulated; Evaluation; Fluorescence; Fluorescent Dyes; Growth; Hand; Image; Implant; In Situ; In Vitro; Infiltration; Label; Left; Malignant Neoplasms; Medical; Medical Research; Medicine; Methodology; Methods; Mission; Monitor; Orthopedics; Outcome; Patients; Photobleaching; Polymers; Process; Property; Proteins; Quantum Dots; Research; Resistance; Sampling; Science; Structure; Therapeutic; Time; Tissue Engineering; Tissues; Toxic effect; Treatment Efficacy; Work; base; biodegradable polymer; bioimaging; biomaterial compatibility; cancer cell; cellular imaging; cost; design; imaging probe; implant material; implantable device; in vivo; in vivo regeneration; innovation; interest; malignant breast neoplasm; medical implant; meetings; molecular imaging; mouse model; nanomedicine; nanoparticle; novel; oncology; quantum; scaffold; success; theranostics; tool; uptake

DESCRIPTION (provided by applicant): Biodegradable polymers have been fabricated into various biomedical implants such as drug delivery nanoparticles, tissue engineering scaffolds, and orthopedic devices. Using biodegradable polymers as implant materials is beneficial as the implants may be degraded and cleared by the body once their missions are complete, leaving no foreign materials in the body. On the other hand, florescent labeling and imaging have fueled the significant growth of life science and medical research due to the increasing demands on analyzing biomolecules, tracking biological process, and visualizing diseases and therapeutic efficacy. The most common fluorescent imaging agents include organic dyes, fluorescent proteins and quantum dots (QDs). The discovery of fluorescent QDs has revolutionized the field of molecular imaging, especially in oncology applications. However, progress made in the past has not alleviated much on their high cost and intrinsic toxicity concerns which substantially hinder their clinical use in patients. As alternatives, fluorescent dyes suffer from photobleaching and fluorescent proteins are dim in vivo and hard to manipulate. It is noteworthy that all the above imaging agents are just "imaging agents". They cannot act alone as medical implants to serve as drug delivery vehicles or tissue engineering scaffolds. Combining biomedical implants and imaging agents for drug delivery and tissue engineering has been a significant focus of research in the past few years. For drug delivery, a significant challenge is to develop multifunctional nanoparticles that can be used to track drug delivery processes and determine therapeutic efficiency in real-time. Although conjugating organic dyes to, or encapsulating QDs in, biodegradable polymers was considered as a significant step in addressing above challenges, it does not address the concerns on their toxicity and low dye-to- nanoparticle labeling ratio for in vivo applications. For tissue engineering, obtaining in-situ and real-time information on scaffold degradation and tissue infiltration/regeneration in vivo, without traumatically explanting samples or sacrificing animals, is an unaddressed challenge. Using safe biodegradable implant polymers that intrinsically emit detectable fluorescence in vivo would address the above challenges in drug delivery and tissue engineering, as well as open new windows for other biological and biomedical applications based on fluorescence labeling and imaging. However, such biomaterials have not been available. Therefore, the objectives of the proposed work are to 1) discover novel in-vivo safe, wholly-biodegradable, photoluminescent (implant) polymers (BPLP), without conjugating organic dyes or semiconducting quantum dots (QDs), and 2) to develop biodegradable polymeric "QDs" (BPLP nanoparticles) promising for bioimaging, exemplified by in vivo breast cancer targeting and imaging. The expected outcomes of the proposed work are that we will understand the mechanisms behind the unique photoluminescent properties of BPLPs, and that we will establish a methodology to expand the BPLP into different types of biodegradable implant polymers. We will demonstrate their novelty and utility by developing biodegradable BPLP nanoparticles (biodegradable polymeric "QDs") for cell labeling and imaging applications, exemplified by cancer cell targeting and imaging in vivo. The Impacts of this proposal lie in that: 1) Unveiling the intriguing fluorescence mechanism and the methods necessary for the syntheses of biodegradable photoluminescent polymers will significantly advance biomaterials science; and 2) the development of BPLPs should bring a paradigm shift in the use of biodegradable implant biomaterials in a broad range of biological and biomedical fields including biosensing, cellular imaging, drug delivery, tissue engineering, and theranostic nanomedicine. PUBLIC HEALTH RELEVANCE: The success of this proposal will result in the discovering and understanding the only kind of biodegradable photoluminescent polymers (BPLPs) that intrinsically emit detectable fluorescence from the body. Based on our recent exciting development on BPLPs, we propose to further unveil the intriguing fluorescence mechanism of BPLPs and develop a methodology for custom-designing multiple classes of BPLPs to meet the versatile needs in biology and medicine. We will also demonstrate BPLP nanoparticles (biodegradable polymeric "quantum dots") as safe in vivo imaging probes for cancer targeting and imaging. Traditional imaging agents such as organic dyes or quantum dots (QDs) are just "imaging agents". They cannot act as implant materials such as drug delivery vehicles or tissue engineering scaffolds. BPLPs are the only polymeric biomaterials that can serve as not only in vivo safe implant materials but also in vivo fluorescent imaging probes without incorporating traditional organic dyes or QDs thus eliminating concerns on photobleaching, low dye-conjugation ratio, and toxicity for in vivo medical applications. The success of this proposal will innovate the biodegradable implant polymers, result in new tools and methods for tracking drug delivery process and therapeutic efficacy, and monitoring structure, composition, and function of engineered tissues in real time quantitatively and non-invasively. The development of BPLPs will have huge impacts on a broad range of fields in biology and medicine including biosensing, cellular imaging, drug delivery, tissue engineering, and theranostic nanomedicine.

描述(申请人提供)：可生物降解的聚合物已被制造成各种生物医学植入物，如药物输送纳米粒、组织工程支架和整形外科设备。使用可生物降解的聚合物作为植入物材料是有益的，因为植入物一旦完成任务，就可以被人体降解和清除，体内不会留下异物。另一方面，由于分析生物分子、跟踪生物过程、可视化疾病和治疗效果的需求日益增长，荧光标记和成像技术推动了生命科学和医学研究的显著发展。最常见的荧光显像剂包括有机染料、荧光蛋白和量子点。荧光量子点的发现彻底改变了分子成像领域，尤其是在肿瘤学中的应用。然而，过去取得的进展并没有缓解它们的高成本和内在毒性问题，这些问题严重阻碍了它们在患者中的临床应用。作为替代品，荧光染料会受到光漂白的影响，而荧光蛋白在体内是模糊的，很难操作。值得注意的是，上述显像剂都只是“显像剂”。它们不能单独作为医疗植入物作为药物输送载体或组织工程支架。将生物医学植入物和显像剂结合起来用于药物输送和组织工程是过去几年的一个重要研究重点。对于药物输送来说，一个重大的挑战是开发多功能纳米颗粒，这种纳米颗粒可以用于跟踪药物输送过程并实时确定治疗效率。尽管将有机染料连接到可生物降解聚合物上或将量子点包裹在可生物降解聚合物中被认为是应对上述挑战的重要一步，但它并没有解决人们对它们的毒性和低染料/纳米颗粒标记比的担忧，用于体内应用。对于组织工程来说，在没有创伤地移植样本或牺牲动物的情况下，获得关于支架在体内的降解和组织渗透/再生的原位和实时信息是一个尚未解决的挑战。使用安全的可在体内发出可检测到的荧光的植入物聚合物将解决药物输送和组织工程中的上述挑战，并为基于荧光标记和成像的其他生物和生物医学应用打开新的窗口。然而，这样的生物材料还没有出现。因此，这项工作的目标是1)发现新型体内安全的、完全生物可降解的光致发光(BPLP)聚合物(BPLP)，而不需要偶联有机染料或半导体量子点(QD)，以及2)开发有望用于生物成像的可生物降解的聚合物量子点(BPLP纳米颗粒)，以体内乳腺癌靶向和成像为例。这项拟议工作的预期结果是，我们将了解BPLP独特的光致发光特性背后的机制，并将建立一种方法来将BPLP扩展到不同类型的可生物降解植入聚合物中。我们将通过开发可生物降解的BPLP纳米颗粒(可生物降解的聚合物量子点)来展示它们的新颖性和实用性，用于细胞标记和成像应用，例如体内癌细胞靶向和成像。这一提议的影响在于：1)揭示有趣的荧光机制和合成可生物降解发光聚合物所需的方法将显著促进生物材料科学；2)BPLP的开发将带来生物可降解植入生物材料在广泛的生物和生物医学领域的使用范式的转变，包括生物传感、细胞成像、药物输送、组织工程和治疗纳米医学。 与公共健康相关：这项提议的成功将导致发现和了解唯一一种从体内发出可检测到的荧光的可生物降解的光致发光聚合物(BPLP)。基于我们最近对BPLP的令人兴奋的研究进展，我们建议进一步揭示BPLP有趣的荧光机制，并开发一种定制设计多类BPLP的方法，以满足生物和医学中的多种需求。我们还将展示BPLP纳米颗粒(可生物降解的聚合物“量子点”)作为安全的体内成像探针，用于癌症靶向和成像。传统的显像剂，如有机染料或量子点(Qds)，都只是“显像剂”。它们不能作为植入材料，如药物输送载体或组织工程支架。BPLP是唯一一种既可以作为体内安全的植入材料，也可以作为体内荧光成像探针的聚合物生物材料，不需要添加传统的有机染料或量子点，从而消除了对光漂白、低染料结合率和体内医疗应用的毒性的担忧。该方案的成功将创新可生物降解的植入聚合物，产生跟踪药物传递过程和治疗效果的新工具和方法，并实时、定量和非侵入性地监测工程组织的结构、组成和功能。BPLPS的发展将对生物和医学的广泛领域产生巨大影响，包括生物传感、细胞成像、药物递送、组织工程和治疗鼻腔纳米医学。