Enhanced intracellular delivery of bcg cell wall skeleton into bladder cancer cells using liposomes functionalized with folic acid and pep-1 peptideopen access
- Authors
- Yoon H.Y.; Yang H.M.; Kim C.H.; Goo Y.T.; Hwang G.Y.; Chang I.H.; Whang Y.M.; Choi Y.W.
- Issue Date
- Dec-2019
- Publisher
- MDPI AG
- Keywords
- Bacillus Calmette–Guérin; Bladder cancer; Cell wall skeleton; Cell-penetrating peptide; Folate; Ligand; Liposome; Targeted delivery
- Citation
- Pharmaceutics, v.11, no.12
- Journal Title
- Pharmaceutics
- Volume
- 11
- Number
- 12
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/38930
- DOI
- 10.3390/pharmaceutics11120652
- ISSN
- 1999-4923
1999-4923
- Abstract
- 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. 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. 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. 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. © 2019 by the authors.
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