산화 스트레스 반응성 물리화학적 변형을 갖는 전도성 탄소복합체 하이드로젤 기반 치료기술 = Oxidative Stress-Responsive Physico-Chemical Deformation of Conductive Polymer Dot-Hydrogel for Theragnosis

다국어 초록 (Multilingual Abstract)

Pathological microenvironments characterized by excess reactive oxygen species (ROS) play a pivotal role in diseases such as cancer and chronic kidney disease (CKD). For instance, tumors develop an acidic extracellular and ROS-rich intracellular milieu that promotes cancer progression, while failing kidneys in CKD endure chronic inflammation and oxidative stress that drive fibrosis. Conventional diagnostics (e.g., SERS, SPR) and therapies (e.g., antioxidants, chemotherapy) often lack specificity or cause collateral damage. Here, we present two stimuli-responsive conductive polymer dot–hydrogel systems that undergo oxidative stress-triggered physicochemical changes for monitoring and therapy. In the first system, a tumor microenvironment-responsive hydrogel was developed by embedding dsCD-PD(HA) nanoparticles with ROS-cleavable diselenide bonds and pH-sensitive boronate ester bonds into a mineralized polyacrylic acid hydrogel matrix. Under acidic condition, and high levels of H₂O₂, these bonds cleave to enable optical and electrical differentiation of cancer cells over normal cells. This hydrogel also demonstrates selective cancer cell targeting, biocompatibility, and wireless interfacing for real- time monitoring. In the second system, a fibrosis-responsive therapeutic hydrogel was synthesized by embedding diselenide-crosslinked polymer dots capsulating a Pygo2 silencer gene (shPygo2) in a PVA/CHI-GA matrix. In an oxidative fibrotic milieu, cleavage of the diselenide bonds imparts ROS scavenging and transforms the hydrogel into a more elastic state with distinct adhesive and impedance changes, providing a built-in indicator of elevated ROS. Concurrently, the released shPygo2 suppresses fibrotic factors (e.g., Pygo2 and α-SMA), attenuating scar formation and preserving renal function in murine models of kidney fibrosis. Both hydrogel systems are highly biocompatible and illustrate a versatile strategy for real-time detection of pathological oxidative stress and therapeutic care and management in diseases such as cancer and kidney fibrosis.

목차 (Table of Contents)

• Overall introduction 1
• Chapter I. Cancer Intra and Extracellular Microenvironment-Responsive Electrical Signal of Touchable Conductive Hydrogel 3
• I. Introduction 4
• II. Objective 7
• III. Experimental Section 8
• IV. Results and Discussion 15
• V. Conclusion 61
• VI. Abstract 63
• Chapter II. Oxidative Stress-Responsive Chemo-Physical Deformation of Hydrogel with Pygo 2 Knockdown for the Prevention of Kidney Fibrosis 64
• I. Introduction 65
• II. Objective 68
• III. Experimental Section 69
• IV. Results and Discussion 81
• V. Conclusion 131
• VI. Abstract 133