Peptide-functionalized graphene as a tumor-activable theranostic system
펩타이드 수식 그래핀을 이용한 종양조직 활성화 진단/치료 시스템
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- theranostics; graphene nanosheet; tumor microenvironment; matrix metalloproteinase; anticancer effect
- 학위논문 (석사)-- 서울대학교 대학원 : 약학대학 약학과(물리약학전공), 2017. 2. 오유경.
- Simultaneous cancer therapy and diagnosis, termed theranostics, have received considerable attention due to requirement of personalized medicine, fulfilling spatiotemporal needs of medication for individual patient. Here, we developed a tumor selectively-activable theranostic system that utilize a conjugate of Cy5.5, polyethylene glycol (PEG), and chimeric peptide which engineered to include a matrix metalloproteinase (MMP)-cleavable sequence, a spacer sequence, and a binding sequence for graphene nanosheet (GN). Cy5.5-PEG-chimeric peptide-modified GN clearly marred the fluorescence of Cy5.5 and cell-penetrating function of therapeutic peptide modified onto GN due to quenching ability of GN, and stealth effect of PEG, respectively. With the presence of MMP, cleavage of chimeric peptide released Cy5.5-PEG from GN, facilitating recovery of fluorescence of Cy5.5 and exposure of cell penetrating peptide on the surface of GN. Deletion of MMP-cleavable sequence in this theranostic system showed negligible differences in fluorescence and antitumor effect upon exposure to MMP. Intravenous administration of MMP-cleavable PEG-GN into SCC7 tumor-bearing mice resulted in 7.2-fold higher fluorescence intensity at tumor site than that of MMP-non-cleavable PEG-GN after 24 hours. Furthermore, cell-penetrating peptide delivered by MMP-cleavable PEG-GN revealed the highest antitumor effect, showing 80% regression of tumor volume than untreated group. Overall, our results demonstrate that tumor-activable PEG-GN could serve as a nano-theranostic system for tumor selective imaging and therapy.