나노 약물을 이용한 대장암 세포의 폐전이 억제
Stimuli responsive nanoparticles release piperlongumine to inhibit pulmonary metastasis of colorectal carcinoma cells
- 주제(키워드) piperlongumine , core-cross linked nanoparticle
- 발행기관 아주대학교
- 지도교수 황성철
- 발행년도 2018
- 학위수여년월 2018. 8
- 학위명 박사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000027968
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Redox-responsive nanoparticles having a diselenide linkage were synthesized to target pulmonary metastasis of cancer cells. Methoxy poly (ethylene glycol)-grafted chitosan (ChitoPEG) was crosslinked using selenocystine-acetyl histidine (Ac-histidine) conjugates (ChitoPEGse) for stimuli-responsive delivery of piperlongumine (PL). ChitoPEGse nanoparticles swelled in an acidic environment and became partially disintegrated in the presence of H2O2 10mM, resulting in an increase of particle size and in a size distribution having multimodal pattern. PL release increased under acidic conditions and in the presence of H2O2. Uptake of ChitoPEGse nanoparticles (PL NP) showed similar anticancer activity in vitro against A549 and CT26 cells compared to PL itself. PL NP showed superior anticancer and anti-metastatic activity in an in vivo CT26 cell pulmonary metastasis mouse model. Furthermore, an immunofluorescence imaging study demonstrated that PL NP conjugates were specifically delivered to the tumor mass in the lung. Conclusively, ChitoPEGse nanoparticles were able to be delivered and released to cancer cells with an acidic- or redox state-sensitive manner and then were selectively targeted to pulmonary metastasis of cancer cells since ChitoPEGse nanoparticles have both pH- and redox-responsiveness.
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TABLE OF CONTENTS
ABSTRACT ⅰ
TABLE OF CONTENTS ⅲ
LIST OF FIGURES ⅴ
I. INTRODUCTION 1
II. MATERIALS AND METHODS 4
A. Materials 4
B. Synthesis of ChitoPEGse nanocomposite 4
C. Fabrication of PL-incorporated ChitoPEGse nanocomposites 7
D. Characterization of nanoparticles 8
E. Cell culture 8
F. MTT assay 9
G. Wound healing assay 10
H. Western blotting 10
I. Immunofluorescence staining 11
J. In vivo CT26 pulmonary metastasis model 12
K. Fluorescence imaging of solid tumor-bearing mice 13
L. Immunohistochemistry 13
M. Statistical analysis 14
III. RESULTS 15
A. Synthesis of ChitoPEGse copolymer 15
B. Fabrication of ChitoPEGse nanoparticles and incorporation of PL 16
C. In vitro cell culture experiment 20
D. In vivo study using pulmonary metastasis model 22
IV. DISCUSSION 32
V. CONCLUSION 36
REFERENCE 37
국문요약 45
