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標題: Doxorubicin delivery by polyamidoamine dendrimer conjugation and photochemical internalization for cancer therapy
作者: Lai, P.S.
Lou, P.J.
Peng, C.L.
Pai, C.L.
Yen, W.N.
Huang, M.Y.
Young, T.H.
Shieh, M.J.
關鍵字: photochemical internalization
cancer therapy
intracellular drug-delivery
copolymer-bound doxorubicin
anticancer drugs
ph-controlled activation
ovarian-carcinoma cells
hpma copolymer
期刊/報告no:: Journal of Controlled Release, Volume 122, Issue 1, Page(s) 39-46.
摘要: Coupling anticancer drugs to synthetic polymers is a promising approach to improve the efficacy and reduce the side effects of these drugs. The pH-activated polymer has been demonstrated to be a successful drug delivery vehicle system, whereas the photochemical internalization (PCI) was invented for site-specific delivery of membrane impermeable macromolecules from endocytic vesicles into the cyrosol. In this study, doxorubicin (DOX) was conjugated to polyamidoamine (PAMAM) dendrimers via pH-sensitive and -insensitive linkers and was combined with different PCI strategies to evaluate the cytotoxic effects. Our results showed that both PCI strategies significantly improved the cytotoxicity, of free DOX on Ca9-22 cells at higher concentrations. The 'light after' PCI treatment was efficient in releasing DOX from the PAMAM-hyd-DOX conjugates, resulted in more nuclear accumulation of DOX and more cell death through synergistic effects. On the other hand, antagonism was observed when 'light before' PCI combined with PAMAM-hyd-DOX conjugate. The distribution of PAMAM-amide-DOX was mainly cytosolic with or without PCI treatments. Both PCI strategies failed to improve the cytotoxicity of PAMAM-amide-DOX conjugates. Our results provide invaluable information in the future design of drug-polymer complexes for multi-modality cancer treatments. (c) 2007 Elsevier B.V. All rights reserved.
ISSN: 0168-3659
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