Time-bomb liposomes for efficient tumor treatment

다국어 초록 (Multilingual Abstract)

This study presents the development of hyaluronated liposomes engineered to undergo time-dependent disassembly in response to hyaluronidase (HAase), underscoring their potential to enhance antitumor therapeutic efficacy. Hyaluronic acid–deoxycholic acid conjugates (HA–DOCA, hereafter referred to as HDOC) were synthesized via covalent linkage between hyaluronic acid (HA) and deoxycholic acid (DOCA). HDOC variants with different DOCA substitution levels (HDOCₓ; x = 0.80, 0.45, 0.20, and 0.10, indicating the molar ratio of DOCA per mole of HA) were incorporated into liposomal membranes formed by the thin-film hydration method using hydrogenated soy phosphatidylcholine (HSPC). HAase was subsequently encapsulated into the liposomes via an extrusion technique, resulting in the final formulation HDOC@Lipo, a time-sensitive drug delivery system programmed to undergo disassembly upon enzymatic activation by HAase. Our experimental results confirmed that HDOC@Lipo containing the antitumor agent doxorubicin (DOX) underwent efficient HAase-mediated cleavage of HA, leading to controlled liposomal destabilization and accelerated DOX release. Collectively, these findings establish HDOC@Lipo as a programmable drug delivery platform capable of time-dependent and enzyme-triggered drug release.

목차 (Table of Contents)

• Acknowledgement
• Contents ⅰ
• List of Figures ⅱ
• Ⅰ. Time-dependent drug-releasing liposomes for efficient tumor
• treatmentAbstract 1
• 1. Abstract 2
• 2. Introduction 4
• 3. Materials and methods 7
• 4. Result and discussion 16
• 5. Conclusion 36
• 6. References 37
• Ⅱ. 국문 논문제출서 42
• Ⅲ. 국문 인준서 43
• Ⅳ. Abstract in Korean 44