Engineered Anisotropic Biphasic Nanoparticles for Bio-Therapeutic and Pharmaceutical Technologies

本研究提出了一种新的纳米制造范式，用于各向异性的微纳米粒子和纳米粒子，称为Janus粒子。虽然这类颗粒最近受到了很多关注，但它们的配方与生物技术不兼容，生物技术需要生物良性聚合物，并且经常需要分阶段递送多种生物治疗因子，但很难实现。这项工作的主要目标是为大规模生产创造新的可生物降解和生物相容性各向异性双相纳米颗粒（ABNPs），能够双重区室化，并结合两种或多种具有交错释放谱的治疗药物。将实现三个具体目标。Aim 1的重点是设计和合成ABNP/ABMPs平台，该平台具有聚合物和脂质材料的不同组合，可自组装成各向异性颗粒。目标2：重点研究聚合物/聚合物和聚合物/脂的建模，为工程ABNP/ABMP的合理设计提供依据；目标3提出通过将ABNP/ABMP纳米制造范例应用于难以治疗的癌症，证明ABNP/ABMP纳米制造范例对双联合药物分阶段递送的更广泛的功能影响。如果成功，该项目将在制药、生物医学、材料工程和分散稳定性方面取得重大进展。此外，多室、生物相容性的颗粒将为主动和被动药物递送载体、组织工程支架和仿生颗粒的设计提供新的途径。更广泛的影响是扩大URM学者参与的机制；开发纳米粒子制造和给药科学与工程工具的课程和专业培训机制。提出了扩大参与的四个具体机制：1)PI将创建研究模块，供所有参与的学生在联合小组会议上完成和讨论研究成果；2)结果将纳入教学课程和实验模块；3)积极参与罗格斯大学已经建立的外展项目；4)与澳门大学的学生进行外展，并在研讨会和会议上进行宣传。

This study proposes a novel nanomanufacturing paradigm for anisotropic micro- and nanoparticles, termed Janus particles. While this class of particles has received much attention recently, their formulations have not been compatible with biotechnology, where bio-benign polymers are called for, and staged delivery of multiple biotherapeutic factors is frequently desired but difficult to achieve. The key goal of this work is to create novel biodegradable and biocompatible anisotropic biphasic nano- particles (ABNPs) for large scale production, capable of dual compartmentalization and incorporation of two or more therapeutic drugs with staggered release profiles. Three specific aims will be pursued. Aim 1 is focused on the design and synthesis of a platform of ABNP/ABMPs with different combinations of polymeric and lipid materials that self-assemble into anisotropic particles. Aim 2 is focused on the modeling of polymer/polymer and polymer/lipid for the rational design of engineered ABNP/ABMP; Aim 3 proposes to demonstrate the broader functional impact of the nanomanufacturing paradigm of ABNP/ABMP on phased delivery of dual-combination drugs by applying these particles for difficult-to-treat cancers.If successful this project will lead to significant advances in pharmaceutics, biomedicine, materials engineering and dispersion stabilization. Furthermore, multicompartmental, biocompatible particles will constitute a new avenue in the design of active and passive drug delivery vehicles, tissue engineering scaffolds, and biomimetic particles. The broader impacts are in the mechanisms for broadening participation of URM scholars; and developing curriculum and professional training mechanisms in the tools for nanoparticle manufacturing and drug delivery science and engineering. Four specific mechanisms for broadening participation are proposed: 1) Study modules will be created by the PI for all participating students to complete and discuss research findings in joint group meetings; 2) Results will be incorporated into teaching courses and laboratory modules; 3) Active participation in already established outreach programs at Rutgers; 4) Outreach to URM students and dissemination in workshops and conferences.