Multifunctional Unimolecular Micelles for Targeted Cancer Therapy

该奖项由威斯康星大学密尔沃基分校材料研究部的生物材料项目授予，旨在研究自组装药物纳米载体，包括脂质体，聚合物胶束和囊泡，其体内稳定性较差，导致靶向差和治疗效果降低。该奖项将有助于开发具有优异的体内稳定性、被动和主动肿瘤靶向能力、理想的粒径、高载药量、可控药物释放和长循环时间的多功能单分子胶束，从而大大提高靶向癌症治疗的疗效并最大限度地减少不良副作用。这些独特的单分子胶束是基于新的生物可降解和/或生物相容性，多臂超支化两亲性嵌段共聚物与活性肿瘤靶向配体。具有64个羟基的超支化聚酯将用作两亲性嵌段共聚物臂聚合的引发剂。本论文将系统地研究分子结构、胶束性质与药物释放行为之间的关系。本科生和研究生都将接受与生物材料研究相关的各种尖端技术的培训。由此产生的知识将改进下一代药物纳米载体的设计，用于靶向癌症治疗诊断学，并被整合到由PI建立的相关课程中。尽管不断努力发现高效的癌症药物，但传统的化疗药物在到达肿瘤组织时仍然表现出较差的特异性，并且经常受到剂量限制性毒性的限制。纳米颗粒由于其被动和主动肿瘤靶向能力而成为期望的抗癌药物载体，从而允许抗癌药物特异性地递送至癌细胞并使对邻近靶组织的非癌细胞的有害毒性最小化。然而，自组装药物纳米载体的一个主要限制是体内不稳定性，这导致治疗效果差。该奖项将有助于开发一种多功能单分子胶束给药系统，该系统具有许多用于靶向癌症治疗的理想特性，从而大大提高癌症患者的护理质量。由此产生的技术将被转移到感兴趣的公司，进一步促进美国的经济增长教育推广活动将通过在威斯康星大学密尔沃基分校的各种推广计划与密尔沃基地区的初中/高中学生进行。

This award by the Biomaterials program in the Division of Materials Research to University of Wisconsin-Milwaukee is to study self-assembled drug nanocarriers, including liposomes, polymer micelles, and vesicles, exhibit poor in vivo stability, leading to poor targeting and reduced therapeutic effect. This award will help to develop multifunctional unimolecular micelles with excellent in vivo stability, passive and active tumor-targeting abilities, desirable particle size, high drug loading capacity, controlled drug release, and long circulation time, thereby greatly increasing the efficacy of targeted cancer therapy and minimizing undesirable side effects. These unique unimolecular micelles are based on novel biodegradable and/or biocompatible, multi-arm hyperbranched amphiphilic block copolymers with active tumor-targeting ligands. A hyperbranched polyester with 64 hydroxyl groups will be used as the initiator for the polymerization of the amphiphilic block copolymer arms. The relationship among the molecular structure, micelle property, and drug delivery behavior will be systematically investigated. Both undergraduate and graduate students will be trained with various cutting-edge techniques related to biomaterials research. The resultant knowledge will improve the design of next-generation drug nanocarriers for targeted cancer theranostics and be integrated into relevant courses established by the PIsDespite continuous and intensive efforts to discover highly effective cancer drugs, conventional chemotherapeutic agents still exhibit poor specificity in reaching tumor tissue and are often restricted by dose-limiting toxicity. Nanoparticulates are desirable anticancer drug carriers due to their passive and active tumor-targeting ability, thereby allowing anticancer drugs to be delivered specifically to the cancer cells and minimizing harmful toxicity to non-cancerous cells adjacent to the target tissue. However, one major limitation with self-assembled drug nanocarriers is in vivo instability, which leads to poor therapeutic effects. This award will help to develop a multifunctional unimolecular micelle drug delivery system with many desirable characteristics for targeted cancer therapy, thereby greatly improving the quality of cancer patient care. The resultant technology will be transferred to interested companies, further promoting economic growth in the U.S. Educational outreach activities will be conducted with Milwaukee-area middle/high school students through the various outreach programs at UW-Milwaukee.