Basic Research - Cancer(구연) (E-008)

Folic Acid and Pep-1 Peptide로 기능화된 리포좀을 이용하여 BCG 세포벽 구조의 방광암 세포내 이동 향상에 관한 연구
중앙대학교병원, 비뇨의학교실
심재헌, 국준희, 최세영, 지병훈, 김진욱, 김태형, 명순철, 장인호
OBJECTIVE: Although bacillus Calmette–Guérin cell wall skeleton (BCG-CWS) might function as a potential substitute for live BCG, its use in the treatment of bladder cancer remains limited owing to issues such as insolubility and micrometer-size following exposure to an aqueous environment.
MATERIALS AND METHODS: Thus, to develop a novel nanoparticulate system for efficient BCG-CWS delivery, liposomal encapsulation was carried out using a modified emulsification-solvent evaporation method (targets: Size, <200 nm; encapsulation efficiency, ~60%). Further, the liposomal surface was functionalized with specific ligands, folic acid (FA), and Pep-1 peptide (Pep1), as targeting and cell-penetrating moieties, respectively.
RESULTS: Functionalized liposomes greatly increased the intracellular uptake of BCGCWS in the bladder cancer cell lines, 5637 and MBT2. The immunoactivity was verified through elevated cytokine production and a THP-1 migration assay. In vivo antitumor efficacy revealed that the BCG-CWS-loaded liposomes effectively inhibited tumor growth in mice bearing MBT2 tumors. Dual ligand-functionalized liposome was also superior to single ligand-functionalized liposomes. Immunohistochemistry supported the enhanced antitumor effect of BCG-CWS, with IL-6 production and CD4 infiltration.
CONCLUSIONS: Thus, we conclude that FA- and Pep1-modified liposomes encapsulating BCG-CWS might be a good candidate for bladder cancer treatment with high target selectivity.
keywords : peptide, targeted delivery, ligand