Creating Safe Biodegradable Photoluminescent Implant Polymers

描述（由申请人提供）：生物可降解聚合物已被制成各种生物医学植入物，如药物递送纳米颗粒、组织工程支架和矫形器械。1 -9使用生物可降解聚合物作为植入物材料是有益的，因为一旦植入物完成任务，植入物就可以降解并被身体清除，不会在体内留下异物。另一方面，由于对分析生物分子、跟踪生物过程以及可视化疾病和治疗效果的需求不断增加，荧光标记和成像推动了生命科学和医学研究的显著增长。最常见的荧光成像剂包括有机染料、荧光蛋白和量子点（QD）。荧光量子点的发现彻底改变了分子成像领域，特别是在肿瘤学应用中。然而，过去取得的进展并没有大大缓解其高成本和内在毒性的问题，这大大阻碍了其在患者中的临床应用。作为替代，荧光染料遭受光漂白，并且荧光蛋白在体内是暗淡的并且难以操纵。值得注意的是，上述所有显像剂都只是“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。结合生物医学植入物和成像剂的药物输送和组织工程一直是一个重要的研究重点，在过去的几年。对于纳米颗粒药物递送，一个重大的挑战是开发多功能纳米颗粒，可用于跟踪药物递送过程并实时确定治疗效率。尽管将有机染料缀合至生物可降解聚合物或将QD包封在生物可降解聚合物中被认为是解决上述挑战的重要步骤，但其并未解决关于其毒性和用于体内应用的低染料与纳米颗粒标记比率的担忧。对于组织工程，获得关于支架降解和体内组织浸润/再生的原位和真实的时间信息，而不创伤性地破坏样品或牺牲动物，是一个未解决的挑战。使用安全的可生物降解的植入聚合物，固有地在体内发射可检测的荧光，将解决药物递送和组织工程中的上述挑战，以及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可用。因此，该提议的目的是发现新的体内安全的、完全可生物降解的光致发光聚合物（BPLP），而不缀合有机染料或半导体量子点（QD），并且其将有希望用于生物成像和医学植入应用，例如通过在体内使用BPLP纳米颗粒（可生物降解的聚合物“QD”）跟踪癌症转移。拟议工作的预期成果是，我们将了解BPLP独特的光致发光特性背后的机制，并且我们将建立一种方法来将BPLP扩展到不同类型的可生物降解聚合物中。我们将通过开发用于生物标记和成像应用的可生物降解的BPLP纳米颗粒（可生物降解的聚合物“QD”）来展示它们的新奇和实用性，例如通过跟踪体内癌细胞迁移。本研究的意义在于：1）揭示了生物可降解光致发光聚合物的荧光机理，为生物材料科学的发展提供了新的思路和方法;和2）BPLPs的发展将在生物传感、细胞成像、药物递送、组织工程等广泛的生物和生物医学领域中带来可生物降解的植入生物材料的使用的范式转变，和治疗诊断纳米医学。

DESCRIPTION (provided by applicant): Biodegradable polymers have been fabricated into various biomedical implants such as drug delivery nanoparticles, tissue engineering scaffolds, and orthopedic devices.1-9 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. One 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 nanoparticle 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 objective of this proposal is to discover novel in-vivo safe, wholly-biodegradable, photoluminescent polymers (BPLP), without conjugating organic dyes or semiconducting quantum dots (QDs), and which will be promising for bioimaging and medical implant applications, exemplified by tracking cancer metastasis using BPLP nanoparticles (biodegradable polymeric "QDs") in vivo. 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 polymers. We will demonstrate their novelty and utility by developing biodegradable BPLP nanoparticles (biodegradable polymeric "QDs") for biological labeling and imaging applications, exemplified by tracking cancer cell migration in vivo. The Impacts of this proposal lie in that: 1) Unveiling the intriguing fluorescence mechanism and the methods for custom-designing biodegradable photoluminescent polymers will significantly contribute to biomaterials science; and 2) the development of BPLPs should bring paradigm shifts on 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.