S-Space College of Engineering/Engineering Practice School (공과대학/대학원) Dept. of Chemical and Biological Engineering (화학생물공학부) Theses (Ph.D. / Sc.D._화학생물공학부)
Protease Activatable Peptide Depot for Photodynamic Therapy and Riboflavin-Induced Hyaluronic acid/Peptide Hydrogel for Bio-Applications
단백질 분해효소에 의한 활성화 펩타이드 디포를 이용한 광역동 치료 및 리보플라빈에 의한 히알루론산/펩타이드 하이드로젤의 생물의학적 응용
- 공과대학 화학생물공학부
- Issue Date
- 서울대학교 대학원
- Photodynamic therapy; Internalizing RGD (iRGD); Activatable photosensitizer; Subcutaneous depot; Sustained release; Hyaluronic acid hydrogel; Tyrosine-rich peptides; Riboflavin; Photo-crosslinking; Wound healing
- 학위논문 (박사)-- 서울대학교 대학원 : 공과대학 화학생물공학부, 2018. 2. 이윤식.
- Peptides are widely studied in various biological applications because of their natural origins, biocompatibility, and diverse functions. One of the most common researches performed using peptides is associated with drug delivery to cancer. These include various functional peptides such as RGD or MMP-7, which are related to overexpressed factors concerning cancer. Recently, structural features of peptides are gaining great interest, where delicate organization could be achieved by specifically designed sequences. These peptides could be utilized in the fabrication of various biomaterials such as hydrogels.
In chapter 1, a cyclic internalizing RGD peptide (iRGD) derivative (Ppa-iRGDC-BK01) that self-aggregates into a molecular depot was applied to photodynamic therapy (PDT). Ppa-iRGDC-BK01 is designed as an in-situ self-implantable photosensitizer so that it forms depot by itself upon injection, and its molecular activities (cancer cell internalization and photosensitization) are activated by sustained release and tumor-selective proteolytic/reductive cleavage of the iRGD segment. It turned out that the self-aggregation of Ppa-iRGDC-BK01 into depot exerts a multiple-quenching effect to effectively prevent nonspecific phototoxicity and photobleaching, while allowing for its sustained release, tumor accumulation and tumoral activation of photosensitivity over time. Such a single-component photosensitizing molecular depot approach, combined with a strategy of tumor-targeted therapeutic activation, opens up a new way to safer and more precise repetition of PDT through single injection and multiple irradiations.
In chapter 2, Tyramine conjugated hyaluronic acid (HA-Ty) was rheometrically modulated with tyrosine rich peptides (TRP) in hydrogel formation, and its potential as a wound healing agent was tested. Riboflavin-sensitized photo-crosslinking was utilized as a gelation strategy, where riboflavin induces covalent linkages between the phenolic groups of conjugated tyramines under UV irradiation. TRP, as an additive, enhanced the storage modulus of the HA-Ty hydrogel because the tyrosine residues could also participate in the crosslinking with the phenol moieties of the HA-Ty. The HA-Ty/TRP hybrid hydrogels were tested as a plausible healing agent for wound injuries.