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: 8587405
• 负责人: Jian Yang
• 金额: $ 27.21万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 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/8587405
• 关键词: Creating; Safe; Biodegradable; Photoluminescent; Implant

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.

描述（由申请人提供）：可生物降解的聚合物已被制造成各种生物医学植入物，例如药物输送纳米颗粒，组织工程脚手架和骨科设备。1-9使用可生物降解的聚合物作为植入物作为植入物作为植入物是有益的，因为植入物可以被植入物质，而不会由身体脱落并清除材料，而将其置于材料中，而将其置于物质中，而不是材料。另一方面，由于对分析生物分子，跟踪生物学过程以及可视化疾病和治疗功效的需求的增加，另一方面，荧光标签和成像促进了生命科学和医学研究的显着增长。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QD的发现彻底改变了分子成像的领域，尤其是在肿瘤学应用中。但是，过去取得的进步并没有太大的成本和内在毒性问题，这极大地阻碍了他们在患者中的临床使用。作为替代品，荧光染料患有光漂白，荧光蛋白在体内昏暗，难以操纵。值得注意的是，上述所有成像剂只是“成像剂”。他们不能单独用作医疗植入物作为药物输送车辆或组织工程脚手架。在过去几年中，结合生物医学植入物和用于药物递送和组织工程的成像剂一直是研究的重点。对于纳米粒子药物的递送，一个重大挑战是开发可用于跟踪药物输送过程并实时确定治疗效率的多功能纳米颗粒。尽管将有机染料结合到或封装在QD中，但可生物降解的聚合物被认为是应对上述挑战的重要一步，但它并未解决其对其毒性的关注以及对体内应用的低染料到纳米颗粒标记率的关注。对于组织工程，获得脚手架降解和体内组织浸润/再生的现场和实时信息，而没有创伤的样品或牺牲动物，这是一项艰巨的挑战。使用安全生物降解的植入物聚合物在体内发射可检测到的荧光，将解决上述药物输送和组织工程中的挑战，以及基于荧光标记和成像的其他生物学和生物医学应用的开放式新窗口。但是，这种生物材料尚未可用。因此，该提案的目的是发现新型的体内安全，可降解的，可降解的，光致发光的聚合物（BPLP），而无需结合有机染料或半导体量子点（QDS）（QDS），并且可以使用癌症和医疗植入物（bio blimentime）（QDS），使用Blimigantic和Medical植入物（bio）blimentiment callimentimecrest（blimigantiment）（QDS）（QDS）（QDS）（QDS）。 “ QD”）体内。拟议工作的预期结果是，我们将了解BPLPS独特光致发光性能背后的机制，并且我们将建立一种将BPLP扩展到不同类型的可生物降解聚合物的方法。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“ QD”）来证明它们的新颖性和实用性，以用于生物标记和成像应用，这是通过在体内跟踪癌细胞迁移的例证。该提案的影响在于：1）揭示有趣的荧光机制，以及定制设计可生物降解的光粉发光聚合物的方法将显着有助于生物材料科学； 2）BPLP的发展应带来在广泛的生物学和生物医学领域中使用可生物降解的植入物生物材料的范式转移，包括生物传感，细胞成像，药物递送，组织工程和疗法纳米医学。