Lipid–polymer nanoparticles encapsulating curcumin for modulating the vascular deposition of breast cancer cells

Abstract

Vascular adhesion and endothelial transmigration are critical steps in the establishment of distant metastasis by circulating tumor cells (CTCs). Also, vascular inflammation plays a pivotal role in steering CTCs out of the blood stream. Here, long circulating lipid-polymer nanoparticles encapsulating curcumin (NANOCurc) are proposed for modulating the vascular deposition of CTCs. Upon treatment with NANOCurc, the adhesion propensity of highly metastatic breast cancer cells (MDA-MB-231) onto TNF-α stimulated endothelial cells (HUVECs) reduces by ~ 70%, in a capillary flow. Remarkably, the CTC vascular deposition already reduces up to ~ 50% by treating solely the inflamed HUVECs. The CTC arrest is mediated by the interaction between ICAM-1 on HUVECs and MUC-1 on cancer cells, and moderate doses of curcumin down-regulate the expression of both molecules. This suggests that NANOCurc could prevent metastasis and limit the progression of the disease by modulating vascular inflammation and impairing the CTC arrest.

Role of liver ICAM-1 in metastasis

“…The same result was observed when the expression of β2 integrin in C26 cells was reduced via siRNA (Benedicto et al, submitted). Additionally, the expression of other ICAM-1 ligands, such as MUC-1, in breast cells was shown to mediate the adhesion of the malignant cells to HUVECs (25).…”

“…Several adhesion molecules, such as E-selectin, vascular cellular adhesion molecule (VCAM)-1 and ICAM-1, exhibit increased expression in the liver during metastatic invasion (22). Among them, ICAM-1 mediates several stages of the metastatic cascade, including the adhesion of tumor cells to the endothelial wall (23)(24)(25), endothelial cell activation of pro-metastatic signaling pathways (26)(27)(28), tumor cell extravasation (23,29), the recruitment of immune cell populations (28,30,31), the pro-angiogenic response (32) and the transdifferentiation of stellate cells during the desmoplastic response (33,34). This review will focus on the role of ICAM-1 during the different events of the metastatic cascade that drives colonization of the liver by circulating tumor cells, and how it modulates the liver microenvironment to facilitate metastasis.…”

Recent Developments in Application of Polymeric Nanoparticles as Drug Carriers

“…Numerous synthetic and natural polymeric materials, including biodegradable, biocompatible and non-biodegradable substances, have already been used for nanoparticle preparation. Among the synthetic biodegradable polymeric matrices, poly(lactide-co-glycolide) (PLGA) [26,28,34] and poly(D, L-lactide) (PLA) [35] are the most common. Polymeric materials such as poly(methylmethacrylate) (PMMA) [36] and poly(ethylene-co-vinyl acetate) (PEVA) [12] are characterized by satisfying biocompatibility.…”

“…In such a case, an active agent is protected from degradation by a polymeric coat able to be functionalized to specifically recognize the targeted site [28]. Other strategies consist of dispersion of the active substance in the polymeric matrix [24].…”

“…Polymer-based nanoparticles can be used as the carrier for numerous biologically active molecules including drugs [18], proteins [7], monoclonal antibodies [13], nucleic acids [19,20], biological extracts [16,21] and others [22]. This review will be especially concerned with the application of polymer-based nanoparticles for the treatment of various disease entities including bacterial [23,24], fungal [25] and parasitic [26] infections, ulcers [11], hypertension [12], angina [8], glaucoma [9], uveitis [27], asthma [22], cancer [15,28], neurodegenerative disease [29] and many others [30,31]. It deserves to be emphasized that several polymers are characterized by satisfying biocompatibility and predictable biodegradability [9,22] while others are non-degradable or undergo slow degradation [22,32].…”