Tumor microvascular permeability is a key determinant for antivascular effects of doxorubicin encapsulated in a temperature sensitive liposome
- 1 January 2008
- journal article
- research article
- Published by Informa UK Limited in International Journal of Hyperthermia
- Vol. 24 (6), 475-482
- https://doi.org/10.1080/02656730701854767
Abstract
Previous data have demonstrated that doxorubicin (DOX) released from a lysolecithin-containing thermosensitive liposome (LTSL) can shut down blood flow in a human tumor xenograft (FaDu) in mice when the treatment is combined with hyperthermia (HT), suggesting that LTSL-DOX is a potential antivascular agent. To further understand mechanisms of the treatment, we investigated effects of LTSL-DOX (5 mg/kg body weight) plus HT (42°C, 1 h) on microcirculation in another tumor (a murine mammary carcinoma, 4T07) implanted in mouse dorsal skin-fold chambers and dose responses of tumor (FaDu and 4T07) and endothelial cells to LTSL-DOX or free DOX with or without HT. We observed that LTSL-DOX-HT could significantly reduce blood flow and microvascular density in 4T07 tumors. The antivascular efficacy of LTSL-DOX-HT could be enhanced through increasing tumor microvascular permeability of liposomes by using platelet activating factor (PAF). We also observed that the dose responses of FaDu and 4T07 to DOX in vitro were similar to each other and could be enhanced by HT. Taken together, these data suggested that tumor microvascular permeability was more critical than the sensitivity of tumor cells to DOX in determining the antivascular efficacy of LTSL-DOX-HT treatment.Keywords
This publication has 28 references indexed in Scilit:
- Effects of lipid segregation and lysolipid dissociation on drug release from thermosensitive liposomesJournal of Controlled Release, 2005
- Liposome‐encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first‐line therapy of metastatic breast carcinomaCancer, 2001
- Delivery of molecular and cellular medicine to solid tumors1PII of original article: S0169-409X(97)00027-6. The article was originally published in Advanced Drug Delivery Reviews 26 (1997) 71–90.1Advanced Drug Delivery Reviews, 2001
- A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicinBiochemical Pharmacology, 1999
- Enhancement of the Phase Transition Permeability of DPPC Liposomes by Incorporation of MPPC: A New Temperature-Sensitive Liposome for use with Mild HyperthermiaJournal of Liposome Research, 1999
- Thermosensitive liposomes: Extravasation and release of contents in tumor microvascular networksInternational Journal of Radiation Oncology*Biology*Physics, 1996
- Effect of Transvascular Fluid Exchange on Pressure–Flow Relationship in Tumors: A Proposed Mechanism for Tumor Blood Flow HeterogeneityMicrovascular Research, 1996
- Microvascular Permeability of Albumin, Vascular Surface Area, and Vascular Volume Measured in Human Adenocarcinoma LS174T Using Dorsal Chamber in SCID MiceMicrovascular Research, 1993
- Uptake of adriamycin into large unilamellar vesicles in response to a pH gradientBiochimica et Biophysica Acta (BBA) - Biomembranes, 1986
- EFFECT OF HYPERTHERMIA ON VASCULAR FUNCTION IN NORMAL AND NEOPLASTIC TISSUES*Annals of the New York Academy of Sciences, 1980