Design of RNA-triggered Disassembly Mechanisms in Multi-responsive Polymer Nanocapsules for Personalized Physiological Profiling and Tailored Therapeutics

非技术性：该奖项将开发新的方法来识别患病组织中的特定遗传图谱，并随后仅在靶组织中释放“个性化”药物鸡尾酒或诊断分子。 定位和治疗病变组织的一种方法是注射含有药物的纳米颗粒，这些纳米颗粒将在体内循环，直到它们与病变细胞接触。 纳米颗粒可以被设计成在细胞内分解并释放封装的药物;然而，为了保护健康细胞免受药物的影响，有必要设计仅在患病细胞中分解的纳米颗粒。 这项研究将设计和生产由DNA“双链体”连接在一起的聚合物纳米颗粒，这些DNA“双链体”的序列是部分互补的。 双链体将被设计为仅在DNA或RNA的完全互补链存在下解结合，导致纳米颗粒的分解和任何包封化合物的释放。 PI将产生DNA连接的纳米颗粒，旨在在乳腺癌特异性RNA分子存在的情况下分解，并将测试这些纳米颗粒是否仅在癌细胞内选择性释放模型药物（染料）。 教育工作，实习和研讨会的目的是增加参与和注册的代表性不足的学生在研究活动在特拉华州的大学。技术：这项研究解决了国家工程学院的大挑战，工程更好的药物，通过开发新的方法，最终将允许快速评估患者的遗传图谱和个性化的药物鸡尾酒的释放。 PI方法是将DNA“链置换”生物传感设计并入聚合物纳米载体内，使得DNA界面控制纳米载体稳定性。 特定RNA或DNA序列的识别将导致链置换反应，其使纳米载体不稳定并允许释放包封的药物或诊断剂。 这项工作的主要里程碑包括设计对乳腺癌特异性RNA敏感的DNA链置换设计;将这些DNA双链体掺入嵌段聚合物胶束中;建立RNA介导的纳米载体分解的特异性和有效性;在纳米载体表面添加癌细胞靶向肽;以及在乳腺癌细胞中建立选择性细胞吸收和有效的货物（染料）释放。 教育活动将包括高中实习，毕业生招聘研讨会，以及针对代表性不足的群体的指导工作，通过参与ACS SEED，SWE，Women in Engineering和ACS Scholars Program等计划的PI提供便利。

Nontechnical:This award will develop new methods to identify specific genetic profiles in diseased tissues and subsequently release "personalized" drug cocktails or diagnostic molecules only within the targeted tissues. One way to locate and treat diseased tissues is by injecting drug-containing nanoparticles that will circulate through the body until they come into contact with diseased cells. Nanoparticles can be designed to fall apart inside of cells and release encapsulated drugs; however, to protect healthy cells from receiving the drug, it is necessary to design nanoparticles that only fall apart in diseased cells. This research will design and produce polymer nanoparticles linked together by DNA "duplexes" whose sequences are partially complementary. The duplexes will be designed to unbind only in the presence of a fully complementary strand of DNA or RNA, leading to the disassembly of the nanoparticles and the release of any encapsulated compounds. The PIs will produce DNA-linked nanoparticles designed to disassemble in the presence of breast cancer-specific RNA molecules, and will test whether these nanoparticles will selectively release model drugs (dyes) only within cancer cells. Educational efforts, internships and workshops are aimed at increasing participation and enrollment of underrepresented students in research activities at the University of Delaware.Technical:This research addresses the National Academy of Engineering's Grand Challenge to engineer better medicines by developing new approaches that will ultimately allow rapid assessment of the genetic profiles in patients and the release of personalized drug cocktails. The PIs approach is to incorporate DNA "strand displacement" biosensing designs within polymer nanocarriers such that the DNA interface controls nanocarrier stability. Recognition of specific RNA or DNA sequences will result in a strand displacement reaction that destabilizes the nanocarrier and allows the release of encapsulated drugs or diagnostics. The major milestones in this work include the design of DNA strand displacement designs sensitive to breast cancer-specific RNAs; incorporation of these DNA duplexes within block polymer micelles; establishment of the specificity and efficacy of RNA-mediated nanocarrier disassembly; addition of cancer cell-targeting peptides on the surface of the nanocarriers; and establishment of selective cellular uptake and efficient cargo (dye) release in breast cancer cells. Educational activities will include high school internships, graduate recruitment workshops, and mentoring efforts targeted at underrepresented groups, facilitated through the PIs involvement in programs including ACS SEED, SWE, Women in Engineering, and the ACS Scholars Program.