RRC ID 37546
著者 Liu Q, Jung J, Somiya M, Iijima M, Yoshimoto N, Niimi T, Maturana AD, Shin SH, Jeong SY, Choi EK, Kuroda S.
タイトル Virosomes of hepatitis B virus envelope L proteins containing doxorubicin: synergistic enhancement of human liver-specific antitumor growth activity by radiotherapy.
ジャーナル Int J Nanomedicine
Abstract Bionanocapsules (BNCs) are hollow nanoparticles consisting of hepatitis B virus (HBV) envelope L proteins and have been shown to deliver drugs and genes specifically to human hepatic tissues by utilizing HBV-derived infection machinery. The complex of BNCs with liposomes (LPs), the BNC-LP complexes (a LP surrounded by BNCs in a rugged spherical form), could also become active targeting nanocarriers by the BNC function. In this study, under acidic conditions and high temperature, BNCs were found to fully fuse with LPs (smooth-surfaced spherical form), deploying L proteins with a membrane topology similar to that of BNCs (ie, virosomes displaying L proteins). Doxorubicin (DOX) was efficiently encapsulated via the remote loading method at 14.2%±1.0% of total lipid weight (mean ± SD, n=3), with a capsule size of 118.2±4.7 nm and a ζ-potential of -51.1±1.0 mV (mean ± SD, n=5). When mammalian cells were exposed to the virosomes, the virosomes showed strong cytotoxicity in human hepatic cells (target cells of BNCs), but not in human colon cancer cells (nontarget cells of BNCs), whereas LPs containing DOX and DOXOVES (structurally stabilized PEGylated LPs containing DOX) did not show strong cytotoxicity in either cell type. Furthermore, the virosomes preferentially delivered DOX to the nuclei of human hepatic cells. Xenograft mice harboring either target or nontarget cell-derived tumors were injected twice intravenously with the virosomes containing DOX at a low dose (2.3 mg/kg as DOX, 5 days interval). The growth of target cell-derived tumors was retarded effectively and specifically. Next, the combination of high dose (10.0 mg/kg as DOX, once) with tumor-specific radiotherapy (3 Gy, once after 2 hours) exhibited the most effective antitumor growth activity in mice harboring target cell-derived tumors. These results demonstrated that the HBV-based virosomes containing DOX could be an effective antitumor nanomedicine specific to human hepatic tissues, especially in combination with radiotherapy.
巻・号 10
ページ 4159-72
公開日 2015-1-1
DOI 10.2147/IJN.S84295
PII ijn-10-4159
PMID 26203243
PMC PMC4487236
MeSH Animals Antineoplastic Agents* / chemistry Antineoplastic Agents* / pharmacokinetics Antineoplastic Agents* / pharmacology Cell Line, Tumor Doxorubicin* / chemistry Doxorubicin* / pharmacokinetics Doxorubicin* / pharmacology Humans Liver / metabolism* Liver Neoplasms / metabolism Mice Radiotherapy / methods Viral Envelope Proteins / chemistry* Virosomes* / chemistry Virosomes* / pharmacokinetics Virosomes* / pharmacology Xenograft Model Antitumor Assays
IF 5.115
引用数 12
WOS 分野 PHARMACOLOGY & PHARMACY NANOSCIENCE & NANOTECHNOLOGY
リソース情報
ヒト・動物細胞 HuH-7(RCB1366)