Albumin acts like transforming growth factor β1 in microbubble-based drug delivery
Journal
Ultrasound in Medicine and Biology
Journal Volume
40
Journal Volume
40
Journal Issue
4
Pages
765-774
Start Page
765
End Page
774
Date Issued
2014-04
Author(s)
Abstract
Unlike lipid-shelled microbubbles (MBs), albumin-shelled microbubbles (MBs) have not been reported to be actively targeted to cells without the assistance of antibodies. Recent studies indicate that the albumin molecule is similar to transforming growth factor β (TGF-β) both structurally and functionally. The TGF-β superfamily is important during early tumor outgrowth, with an elevated TGF-β being tumor suppressive; at later stages, this switches to malignant conversion and progression, including breast cancer. TGF-β receptors I and II play crucial roles in both the binding and endocytosis of albumin. However, until now, no specific albumin receptor has been found. On the basis of the above-mentioned information, we hypothesized that non-antibody-conjugated albumin-shelled MBs can be used to deliver drugs to breast cancer cells. We also studied the possible roles of TGF-β1 and radiation force in the behavior of cells and albumin-shelled MBs. The results indicate that albumin-shelled MBs loaded with paclitaxel (PTX) induce breast cancer cell apoptosis without the specific targeting produced by an antibody. Applying either an acoustic radiation force or cavitation alone to cells with PTX-loaded albumin MBs increased the apoptosis rate to 23.2% and 26.3% (p<0.05), respectively. We also found that albumin-shelled MBs can enter MDA-MB-231 breast cancer cells and remain there for at least 24h, even in the presence of PTX loading. Confocal micrographs revealed that 70.5% of the breast cancer cells took up albumin-shelled MBs spontaneously after 1d of incubation. Applying an acoustic radiation force further increased the percentage to 91.9% in our experiments. However, this process could be blocked by TGF-β1, even with subsequent exposure to the radiation force. From these results, we conclude that TGF-β1 receptors are involved in the endocytotic process by which albumin-shelled MBs enter breast cancer cells. The acoustic radiation force increases the contact rate between albumin-shelled MBs and tumor cells. Combining a radiation force and cavitation yields an apoptosis rate of 31.3%. This invitro study found that non-antibody-conjugated albumin-shelled MBs provide a useful method of drug delivery. Further invivo studies of the roles of albumin MBs and TGF-β in different stages of cancer are necessary. ? 2014 World Federation for Ultrasound in Medicine & Biology.
Subjects
Albumin-shelled microbubbles; Cavitation; Paclitaxel; Radiation force
SDGs
Other Subjects
Acoustic emissions; Acoustic radiators; Acoustic wave propagation; Acoustic wave transmission; Antibodies; Cavitation; Cell death; Diseases; Drug delivery; Molecular biology; Radiotherapy; Tumors; Acoustic radiation force; Apoptosis rates; Breast cancer cells; Different stages; Microbubbles; Paclitaxel; Radiation forces; Transforming growth factors; Loading; albumin; albumin receptor; liposome; paclitaxel; transforming growth factor beta1; apoptosis; article; cancer growth; controlled study; cytoplasm; cytotoxicity; drug delivery system; endocytosis; endothelium cell; flow cytometry; human; human cell; microbubble; microcirculation; phagocytosis; priority journal; protein protein interaction; radiation; sequence homology; signal transduction; Albumin-shelled microbubbles; Cavitation; Paclitaxel; Radiation force; Transforming growth factor β(1); Albumins; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Capsules; Cell Line, Tumor; High-Energy Shock Waves; Humans; Paclitaxel; Sonication; Transforming Growth Factor beta1; Treatment Outcome
Type
journal article