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Doxorubicin delivery by polyamidoamine dendrimer conjugation and photochemical internalization for cancer therapy

2007; Elsevier BV; Volume: 122; Issue: 1 Linguagem: Inglês

10.1016/j.jconrel.2007.06.012

1873-4995

Ping‐Shan Lai, Pei‐Jen Lou, Cheng‐Liang Peng, Chin‐Ling Pai, Wei-Nen Yen, Ming‐Yi Huang, Tai‐Horng Young, Ming‐Jium Shieh,

Advanced biosensing and bioanalysis techniques

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 cytosol. 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.