Cationic Diblock Polymer-Drug Conjugate-Based Nanoparticles for Drug-Gene Co-Delivery

非技术性：这一奖项由纽约州立大学布法罗分校材料研究部的生物材料计划授予该大学，旨在开发一种在癌症治疗中具有潜在应用的新型药物-基因联合传递系统。将制备每个分子具有两个构建块的可生物降解聚合物。一个构建块将连接化学上的抗癌药物；另一个构建块将携带正电荷，并可以物理吸附带负电荷的抗癌基因。这种可生物降解的聚合物将在水溶液中组装形成核壳纳米颗粒(NPs)，其中内核域用于载药，外壳域用于基因载药。将进行全面的研究，以考察可生物降解聚合物的制备和组装，组装的纳米粒子的治疗输送和降解行为，以及药物-基因共输送系统对癌细胞和组织的生物医学效应。该项目可为进一步开发药物-基因联合疗法用于癌症的协同治疗奠定重要基础。将通过YouTube播放聚合物短视频和针对当地学校儿童的教育活动进行外联。来自代表性不足群体的学生的研究参与将得到保障。还将做出大量努力来更新一本经典的聚合物教科书。技术：该项目的目标是开发多功能可生物降解纳米载体，不仅能够非竞争性地高负载药物和基因，而且能够持续释放这些治疗药物。为此，具有药物偶联嵌段和阳离子嵌段的两亲性可生物降解双嵌段聚合物药物结合物(PDC)被设计为制备多功能纳米粒子的新型生物材料，将组合治疗、控制释放、成像、靶向和生物降解性集成到一个定义良好的纳米系统中，以实现药物和基因的精确传递。将制备定义良好的双嵌段PDCs，以及相应的具有抗癌药物共轭核心和阳离子壳层的组装纳米粒子，并对其进行表征。将研究药物结合、与抗癌基因的络合、药物/基因释放谱、纳米粒的降解行为和多功能化。将进行乳腺癌模型的体外和体内研究，并评价具有偶联药物和复合基因的多功能纳米粒与各种对照组的抗癌效果。这些核动力源可以作为详细的系统研究的独特平台，以了解和优化制约联合交付办法成功的参数。该项目将为各种学生提供绝佳的跨学科研究机会，包括来自代表性不足群体的学生。将开展广泛的教育宣传活动。

Non-Technical: This award by the Biomaterials program in the Division of Materials Research to University at Buffalo, The State University at New York is to develop a novel drug-gene co-delivery system with potential applications in cancer treatment. Biodegradable polymers with two building blocks per molecule will be prepared. One building block will attach chemically anticancer drugs; the other building block will carry positive charges and can physically adsorb negatively-charged anticancer genes. The biodegradable polymers will assemble to form core-shell nanoparticles (NPs) in aqueous solutions, with inner core domains for drug loading and outer shell domains for gene loading. Comprehensive studies will be conducted to investigate the preparation and assembly of the biodegradable polymers, therapeutic delivery and degradation behavior of the assembled NPs, as well as the biomedical effects of the drug-gene co-delivery system on cancer cells and tissues. This project can lay a significant foundation for the further development of drug-gene combination therapies for the synergetic treatment of cancers. Outreach will be conducted through YouTube broadcasting of short polymer videos and educational activities directed to kids in local schools. Research participation of students from underrepresented groups will be guaranteed. Substantial efforts will also be made to update a classic polymer textbook.Technical: The goal of this project is to develop multifunctional biodegradable nanocarriers enabling not only noncompetitive high loadings of drugs and genes but also sustained release of these therapeutics. To this end, amphiphilic biodegradable di-block polymer-drug conjugates (PDCs) with a drug-conjugated block and a cationic block are designed as novel biomaterials for the preparation of multifunctional NPs, to integrate combination therapy, controlled release, imaging, targeting and biodegradability into one well-defined nanoscopic system for the precise delivery of both drug and gene. Well-defined di-block PDCs, as well as the corresponding assembled NPs with anticancer drug-conjugated cores and cationic shells, will be prepared and characterized. Drug conjugation, complexation with anticancer genes, drug/gene release profile, degradation behavior and multifunctionalization of the NPs will be studied. In vitro and in vivo studies using breast cancer models will be performed, and the anticancer efficacy of the multifunctional NPs with conjugated drug and complexed gene as compared to various controls will be evaluated. These NPs can serve as unique platforms for detailed systematic studies to understand and optimize the parameters governing the success of the co-delivery approach. The project will provide excellent interdisciplinary research opportunities for various students, including these from underrepresented groups. Broad educational outreach activities will be conducted.