Charged Electrostatically Assembled Nanoparticles for Targeted Delivery
带电的静电组装纳米颗粒——用于靶向递送
Paula T. Hammond
ABSRACT
A layer-by-layer (LbL) technique toward construction of nanostructured nanoparticles provides a unique platform approach for drug delivery and nanomedicine. We have generated LbL outer layers that provide effective stealth properties, with long systemic plasma blood half-lives and higher tumor accumulation over time, and demonstrate efficacy in advanced breast and lung cancer models in which siRNA targets have been delivered with chemotherapy drug in the same nanoparticle system. We are now examining new siRNA and drug combinations in ovarian cancer. By staging release of different drug components via the adaptation of the nanoparticle structure, we can achieve highly synergistic release behavior in these systems. We have found that certain LbL nanoparticle formulations traffic differently in cells based on the negatively charged polypeptide, and are exploring ways to utilize these differences in affinity for more selective tumor cell binding and deliver within cells. Ongoing work includes addressing barriers to transport of these nanoparticles relevant to tumor or other tissue penetration, and will be discussed, including new work involving the understanding of these trafficking patterns and a means to leverage them toward the delivery of cytokines for activation of the immune system against cancer. Finally, we have also begun investigating how these polymeric colloidal systems undergo release mechanisms when in the tumor microenvironment.
一种用于构建纳米结构纳米颗粒的逐层(LbL)技术为药物递送和纳米医学提供了独特的平台方法。我们制作的LbL外层具有有效的隐身特性，较长的全身血浆半衰期和较高的肿瘤蓄积，并证明了在晚期乳腺癌和肺癌模型中，siRNA靶点与化疗药物在相同的纳米颗粒系统中传递的有效性。我们现在正在检查新的siRNA和卵巢癌的药物组合。通过对纳米颗粒结构的适应来分期释放不同的药物成分，我们可以在这些体系中实现高度协同的释放行为。我们发现，基于负电荷多肽，某些LbL纳米颗粒制剂在细胞中的流量不同，我们正在探索如何利用这些亲和力的差异，以更有选择性地结合肿瘤细胞并在细胞内传递。目前正在进行的工作包括解决与肿瘤或其他组织穿透相关的纳米颗粒的运输障碍，并将进行讨论，包括了解这些运输模式以及利用它们递送细胞因子以激活免疫系统对抗癌症的方法等新工作。最后，我们也开始研究这些高分子胶体系统在肿瘤微环境中的释放机制。
BIOGRAPHY
Professor Paula T. Hammond is the David H. Koch Chair Professor of Engineering at the Massachusetts Institute of Technology, Head of the Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research. Her research in nanomedicine encompasses the development of new biomaterials to enable drug delivery from surfaces with spatio-temporal control. She investigates novel responsive polymer architectures for targeted nanoparticle drug and gene delivery, and is known for her work on nanoparticles to target cancer, and thin film coatings to release factors that regenerate bone and assist in wound healing. More recently, she has worked on nanomaterials systems to treat osteoarthritis and staged release systems for the delivery of vaccines. Professor Paula Hammond was elected into the National Academy of Science in 2019, the National Academy of Engineering in 2017, the National Academy of Medicine in 2016, and the 2013 Class of the American Academy of Arts and Sciences. She has also recently received the American Institute of Chemical Engineers (AIChE) Margaret H. Rousseau Pioneer Award for Lifetime Achievement by a Woman Chemical Engineer in 2019 and gave the Materials Research Society (MRS) David Turnbull Lectureship, 2019. Professor Hammond has published over 330 papers, and over 20 patent applications. She is the co-founder and member of the Scientific Advisory Board of LayerBio, Inc., a member of the Scientific Advisory Board of Moderna Therapeutics and a member of the Board of Alector, Inc.
Paula T. Hammond教授是麻省理工学院David H. Koch首席教授，化学工程系主任，麻省理工学院Koch综合癌症研究所成员。她在纳米医学方面的研究包括开发新的生物材料，使药物从具有时空控制的表面释放。她研究新型响应性聚合物体系结构，用于靶向纳米颗粒药物和基因传递，并以研究靶向癌症的纳米颗粒和释放因子的薄膜涂层而闻名，这些因子可再生骨骼并帮助伤口愈合。最近，她研究了治疗骨关节炎的纳米材料系统，以及用于疫苗输送的释放系统。Paula Hammond教授于2013年入选美国艺术与科学学院，2016年入选美国国家医学院，2017年入选美国国家工程院，2019年入选美国国家科学院。她还获得了2019年美国化学工程师学会(AIChE)Margaret H. Rousseau先锋终身成就奖，并在2019年被授予材料研究学会(MRS)David Turnbull讲师职位。Hammond教授发表了330多篇论文，申请了20多项专利。她是LayerBio, Inc.的联合创始人和科学顾问委员会成员，Moderna Therapeutics的科学顾问委员会成员和Alector, Inc.的董事会成员。