Antiproliferative activity of liposome-encapsulated transforming growth factor-beta against MDA-MB-435 human breast carcinoma cells.
We determined whether transforming growth factor-beta (TGF-beta) could be encapsulated in phospholipid liposomes and then would mediate antiproliferative activity against the sensitive, human breast cancer cell line, MDA-MB-435. TGF-beta was encapsulated in multilamellar liposomes consisting of phosphatidylcholine (PC) or PC and phosphatidylserine (PS) at a 7:3 molar ratio. It was captured in both the aqueous phase and the bilayer lipid (hydrophilic and lipophilic association) and was stable for at least 24 hr of incubation at 37 degrees C in medium that contained 5% fetal bovine serum. In calcium- and magnesium-free Hanks' balanced salt solution, TGF-beta in the internal aqueous compartment was stable for at least five days, even in the presence of trypsin and ethylenediamine tetraacetic acid. TGF-beta (type 1 or 2) in liposomes was active as free-form TGF-beta in mediation of antiproliferative effects. The lipophilic nature of TGF-beta, which resulted in a high capture ratio in liposomes, coupled with exceptional stability, suggested that liposomes could be a carrier for the in vivo use of TGF-beta.
Fan
D
D
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Price
J
J
Schackert
H
H
Seid
C
C
Wilmanns
C
C
Chakrabarty
S
S
Fidler
I J
IJ
D001943:Breast Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D015291:Transforming Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D008081:Liposomes; D015291:Transforming Growth Factors