[3PS-115]
Boosting PD-L1 Checkpoint Therapy by an αPD-L1 Nanocomplex that Releases NO and Remodels Collagen-Rich ECM
발표자이지혜 (포항공과대학교)
연구책임자김원종 (포항공과대학교)
Abstract
The extracellular matrix (ECM) of many solid tumors forms a formidable transport barrier that limits the intratumoral distribution of immune checkpoint inhibitors (ICIs) and restricts cytotoxic T lymphocyte (CTL) entry, ultimately blunting immune checkpoint blockade (ICB). To dismantle this obstacle, we developed a programmable nanocomplex built on TANNylated αPD-L1 and coated with a reactive oxygen species (ROS)–triggered nitric oxide (NO) prodrug. After preferential accumulation in tumors, elevated ROS within the tumor microenvironment (TME) initiates localized NO generation. The NO produced in situ promotes activation of matrix metalloproteinases (MMPs), resulting in accelerated collagen breakdown and loosening of the collagen-dense ECM network. Once the matrix barrier is attenuated, the nanocomplex undergoes pH-dependent disassembly to liberate αPD-L1 within deeper tumor regions, enabling more uniform antibody exposure where penetration is typically limited.