Extracellular matrix (ECM) mechanical properties upregulate cancer invasion, cell contractility, and focal adhesion formation. Alteration in energy metabolism is a known characteristic of cancer cells (i.e., Warburg effect) and modulates cell invasion. There is little evidence to show if collagen density can alter cancer cell metabolism. We investigated changes in energy metabolism due to collagen density in five breast cell lines by measuring the fluorescence lifetime of NADH. We found that only triple-negative breast cancer cells, MDA-MB231 and MDA-MB468 cells, had an increased population of bound NADH, indicating an oxidative phosphorylation (OXPHOS) signature, as collagen density decreased. When inhibiting ROCK and cell contractility, MDA-MB231 cells on glass shifted from glycolysis (GLY) to OXPHOS, confirming the intricate relationship between mechanosensing and metabolism. MCF10A cells showed less significant changes in metabolism, shifting towards GLY as collagen density decreased. The MCF-7 and T-47D, less invasive breast cancer cells, compared to the MDA-MB231 and MDA-MB468 cells, showed no changes regardless of substrate. In addition, OXPHOS or GLY inhibitors in MDA-MB231 cells showed dramatic shifts from OXPHOS to GLY or
Peptide‐based nanomaterials are increasingly gaining popularity due to their specificity, biocompatibility, and biodegradability. In this work, a new multi‐layered peptide‐based biocomposite for targeting MCF‐7 breast cancer cells is developed. The amphipathic Fluorenylmethyloxycarbonyl (Fmoc)‐Leu‐Ser peptide is synthesized, which is conjugated to a tumor‐targeting peptide sequence Gly‐Cys‐Gly‐Asn‐Ser to form Fmoc‐L‐S‐G‐C‐G‐N‐S (FLS) assemblies. To the FLS assemblies, gold nanorods are then attached to develop drug delivery vehicles (DDVs). The DDVs are entrapped with the anti‐cancer drug fulvestrant. Entrapment efficiency is found to be 50.6%. Release studies indicate that irradiating the gold nanorod bound DDVs at NIR wavelength (785 nm) increases drug release by fourfold compared to assemblies that are not irradiated. These results also show higher cytotoxicity and lower cell invasion due to photo‐triggered drug release. Furthermore, distinct actin cytoskeletal changes are observed. Such novel peptide‐based gold nanorod bound DDVs demonstrate potential in dual targeting of MCF‐7 breast cancer cells.
more » « less- NSF-PAR ID:
- 10455317
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Biotechnology Journal
- Volume:
- 15
- Issue:
- 12
- ISSN:
- 1860-6768
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract vice versa . These results provide an important link between cellular metabolism, contractility, and collagen density in human breast cancer. -
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