Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods.

Published

Journal Article

Delivery of chemotherapeutic agents after encapsulation in nanocarriers such as liposomes diminishes side-effects, as PEGylated nanocarrier pharmacokinetics decrease dosing to healthy tissues and accumulate in tumors due to the enhanced permeability and retention effect. Once in the tumor, however, dosing of the chemotherapeutic to tumor cells is limited potentially by the rate of release from the carriers and the size-constrained, poor diffusivity of nanocarriers in tumor interstitium. Here, we report the design and fabrication of a thermosensitive liposomal nanocarrier that maintains its encapsulation stability with a high concentration of doxorubicin payload, thereby minimizing "leak" and attendant toxicity. When used synergistically with PEGylated gold nanorods and near-infrared stimulation, remote triggered release of doxorubicin from thermosensitive liposomes was achieved in a mouse tumor model of human glioblastoma (U87), resulting in a significant increase in efficacy when compared to nontriggered or nonthermosensitive PEGylated liposomes. This enhancement in efficacy is attributed to increase in tumor-site apoptosis, as was evident from noninvasive apoptosis imaging using Annexin-Vivo 750 probe. This strategy affords remotely triggered control of tumor dosing of nanocarrier-encapsulated doxorubicin without sacrificing the ability to differentially dose drugs to tumors via the enhanced permeation and retention effect.

Full Text

Duke Authors

Cited Authors

  • Agarwal, A; Mackey, MA; El-Sayed, MA; Bellamkonda, RV

Published Date

  • June 2, 2011

Published In

Volume / Issue

  • 5 / 6

Start / End Page

  • 4919 - 4926

PubMed ID

  • 21591812

Pubmed Central ID

  • 21591812

Electronic International Standard Serial Number (EISSN)

  • 1936-086X

International Standard Serial Number (ISSN)

  • 1936-0851

Digital Object Identifier (DOI)

  • 10.1021/nn201010q

Language

  • eng