* 일시 : 5/29(목) 16:30 –
* 연사 : 신소영 연사(중앙대학교), 육심명 연사(성균관대학교)
* 장소 : 벤처관 711호
* 제목 : Advancing the development of GLP-1 receptor agonists: PK/PD considerations,
Designing Bio-Responsive Nanocarriers for Tumor Microenvironment Modulation
*초록
Advancing the development of GLP-1 receptor agonists: PK/PD considerations
The development of glucagon-like peptide 1 (GLP-1) receptor agonists has significantly advanced the therapeutic landscape for type 2 diabetes and obesity, offering both glycemic control and weight loss benefits. However, their clinical translation remains challenging due to complex pharmacokinetic (PK) behaviors. We employed highly sensitive and robust LC-MS/MS methods to accurately quantify peptide concentrations in biological matrices, enabling precise PK characterization. By using LC-MS/MS methods, the pharmacokinetics of GLP-1 receptor agonists, including liraglutide, semaglutide, and terzepatide, were comparatively evaluated. To better understand and predict the in vivo pharmacokinetics of these agents, advanced PK modeling strategies were employed, including the development of a target-mediated drug disposition (TMDD) model to characterize the dose-dependent nonlinear PK behavior of GLP-1 receptor agonists. This model effectively captured receptor-mediated clearance and saturation kinetics, offering mechanistic insight into the relationship between dose, exposure, and pharmacodynamic outcomes. Collectively, our approach highlights the utility of integrating sensitive bioanalytical techniques with mechanistic PK modeling to overcome the challenges associated with peptide therapeutics and to accelerate the development of next-generation GLP-1 receptor agonists.
Designing Bio-Responsive Nanocarriers for Tumor Microenvironment Modulation
Recent advances in cancer nanomedicine have emphasized the importance of not only targeting tumor cells directly but also reprogramming the tumor microenvironment (TME) to overcome therapy resistance, immune suppression, and tumor progression. This seminar will delve into the rational design and application of smart, bio-inspired nanocarriers engineered for tumor reprogramming. Specifically, we will explore three emerging strategies in this field: redox-responsive nanoparticles, immune cell-modulating nanocarriers, and antibody–drug conjugates (ADCs).Redox-responsive nanoparticles are designed to exploit the elevated levels of reactive oxygen species (ROS) and reducing agents such as glutathione (GSH) commonly found in tumor tissues. These stimuli-responsive systems enable site-specific drug release, minimizing off-target toxicity while maximizing therapeutic efficacy. We will discuss various design strategies including disulfide linkages, and ROS-cleavable moieties, that allow these nanoparticles to release their payloads in response to redox imbalances in the TME.
The seminar will also cover immune-modulating nanoparticles that are engineered to reprogram the immune landscape of the tumor. These nanocarriers can deliver small molecules, cytokines, or nucleic acids to immune cells such as macrophages, dendritic cells, and T cells, with the aim of reversing immune suppression, promoting pro-inflammatory phenotypes, and enhancing anti-tumor immunity. Examples will include nanoparticles designed to polarize tumor-associated macrophages (TAMs) from M2 to M1 phenotype and those that enhance dendritic cell antigen presentation for improved T cell activation.
Finally, we will examine antibody–drug conjugates (ADCs), which merge the specificity of monoclonal antibodies with the potency of cytotoxic drugs. ADCs represent a clinically validated form of smart nanocarrier that can selectively target tumor-associated antigens, allowing for precise delivery of chemotherapeutics while sparing normal tissues. We will review the components of ADCs—antibody, linker, and payload—as well as current clinical examples and the challenges in improving their therapeutic index.
Together, these technologies represent a powerful toolkit for tumor reprogramming, with the potential to transform cancer treatment through enhanced selectivity, reduced toxicity, and synergistic action with existing immuno- and chemotherapies. The seminar aims to provide students with a comprehensive understanding of how interdisciplinary engineering approaches—drawing from chemistry, immunology, and nanotechnology—are converging to create next-generation precision therapeutics.