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

非技术：该奖项由布法罗大学材料研究部生物材料项目授予纽约州立大学，旨在开发一种新型药物-基因共递送系统，该系统在癌症治疗中具有潜在的应用。将制备每个分子具有两个结构单元的生物可降解聚合物。 其中一个构件将化学地附着抗癌药物;另一个构件将携带正电荷，并且可以物理地吸附带负电荷的抗癌基因。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（NP），具有用于药物负载的内核域和用于基因负载的外壳域。本研究将对生物可降解聚合物的制备和组装、组装纳米粒的治疗递送和降解行为以及药物-基因共递送系统对癌细胞和组织的生物医学效应进行全面的研究。该项目为进一步开发药物-基因联合疗法协同治疗癌症奠定了重要基础。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宣传。将保证代表性不足群体的学生参与研究。技术：本项目的目标是开发多功能生物可降解纳米载体，不仅能够实现药物和基因的非竞争性高载量，而且能够持续释放这些治疗药物。为此，具有药物缀合嵌段和阳离子嵌段的两亲性可生物降解的二嵌段聚合物-药物缀合物（PDCs）被设计为用于制备多功能NP的新型生物材料，以将组合治疗、控制释放、成像、靶向和生物降解性整合到一个定义明确的纳米级系统中，用于药物和基因的精确递送。将制备和表征定义明确的二嵌段PDC以及具有抗癌药物缀合的核和阳离子壳的相应组装的NP。将研究药物缀合、与抗癌基因的络合、药物/基因释放曲线、降解行为和纳米颗粒的多功能化。将使用乳腺癌模型进行体外和体内研究，并将评价具有缀合药物和复合基因的多功能NP与各种对照相比的抗癌功效。这些NP可以作为详细系统研究的独特平台，以了解和优化共同交付方法成功的参数。该项目将为各种学生提供优秀的跨学科研究机会，包括来自代表性不足群体的学生。将开展广泛的教育推广活动。

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.