Original ArticleLipid–polymer nanoparticles encapsulating curcumin for modulating the vascular deposition of breast cancer cells
Graphical Abstract
Tumor cells adhere to the vessel walls and migrate across the endothelium to colonize distant sites. Vascular adhesion molecules, such as ICAM-1 and E-selectin, support the interaction of circulating tumor cells with the inflamed endothelium facilitating cell extravasation. Long circulating nanoparticles loaded with curcumin, a potent anti-inflammatory natural product, can modulate the expression of adhesion molecules on both the circulating tumor cells and the inflamed endothelium thus reducing the likelihood of metastasis formation.
Section snippets
Materials and chemicals
Human Fibronectin was obtained from Sigma Aldrich (St. Louis, MO, USA). Curcumin (mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, 98+%) was obtained from Fisher Scientific. XTT kit was obtained from Trevigen (Gaithersburg, Maryland 20877). Anti-human CD54 Purified, Anti-human CD227 (Mucin 1) eFluor615 (clone SM3), Anti-mouse IgG1 APC, and mouse IgG1 K Isotype control PE antibodies were obtained from e-biosciences; Anti-MUC1 purified (clone SM3) was obtained from abcam.
Synthesis and physico-chemical characterization of nanoparticles encapsulating curcumin
Nanoparticles encapsulating curcumin molecules (NANOCurc) were synthesized using an emulsion/solvent evaporation technique, as detailed in the Materials and Methods. NANOCurc comprise a polymeric core, made of poly(lactic-co-glycolic acid) (PLGA); and an external layer, composed of a mixture of natural lipids and poly(ethylene glycol) (PEG) chains, as schematically depicted in the insets of Figure 1, B. The curcumin molecules are dispersed within the hydrophobic PLGA core; whereas the outer
Discussion
It is becoming clearer that systemic inflammation may influence the dissemination of tumor cells by facilitating the vascular arrest of CTCs and their proliferation at distant sites. In vivo studies document that the intravenous injection of LPS into mice may increase by over 40% the vascular deposition of lung carcinoma cells in hepatic sinusoids.16 Also, pulmonary inflammation was shown to enhance the formation of melanoma metastasis in the lungs by over 3 times.17 Furthermore, in obese
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2022, Seminars in Cancer BiologyCitation Excerpt :NSAIDs inhibit the growth of a number of tumors by blocking COX activity and modulating the NF-κB pathway, among other key inflammatory pathways [196]. Curcumin loaded in lipid-polymer NPs called NANOCurc curbs the vascular accumulation of circulating tumor cells [197]. In a different study, researchers loaded docetaxel (DTXL) and curcumin together in curcumin-conjugated cholesteryl-hyaluronic acid nanogels (CHA-CUR) as well as spherical polymeric nano constructs (SPNs), which resulted in a 13-fold tumor suppression [198].
Grants and Conflict of Interests: This work was partially supported by the Cancer Prevention Research Institute of Texas through grant CPRIT RP110262; the National Institutes of Health (NIH, USA) through grants U54CA143837 and U54CA151668. Anna L. Palange and Daniele Di Mascolo acknowledge the Doctoral School of The University of Magna Graecia (Italy) for travel support. Daniele Di Mascolo also acknowledges the support of the EU Commission, the European Social Fund and the department 11 “Culture-Education-University-Research-Technological Innovation-Higher Education” of Calabria Region (POR Calabria FSE 2007/2013).
The authors declare no competing interests.