Cytotoxic chemotherapy continues to be the main therapeutic option for patients with metastatic breast cancer. Several studies have reported a significant association between chronic inflammation, carcinogenesis and the presence of cancer stem cells (CSC). We hypothesized that the use of non-steroidal anti-inflammatory drugs targeted to the CSC population could help reducing tumor progression and dissemination in otherwise hard to treat metastatic breast cancer. Within this study cationic naproxen (NAP)-bearing polymeric nanoparticles (NPs) were obtained by self-assembly and they were coated with hyaluronic acid (HA) via electrostatic interaction. HA-coated and uncoated NAP-bearing NPs with different sizes were produced by changing the ionic strength of the aqueous preparation solutions (i.e. 300 and 350 nm or 100 and 130 nm in diameter, respectively). HA-NPs were fully characterized in terms of physicochemical parameters and biological response in cancer cells, macrophages and endothelial cells. Our results revealed that HA-coating of NPs provided a better control in NAP release and improved their hemocompatibility, while ensuring a strong CSC-targeting in MCF-7 breast cancer cells. Furthermore, the best polymeric NPs formulation significantly (p < 0.001) reduced MCF-7 cells viability when compared to free drug (i.e. 45 ± 6% for S-HA-NPs and 87 ± 10% for free NAP) by p53-dependent induction of apoptosis; and the migration of these cell line was also significantly (p < 0.01) reduced by the nano-formulated NAP (i.e. 76.4% of open wound for S-HA-NPs and 61.6% of open wound for NAP). This increased anti-cancer activity of HA-NAP-NPs might be related to the induction of apoptosis through alterations of the GSK-3β-related COX-independent pathway. Overall, these findings suggest that the HA-NAP-NPs have the potential to improve the treatment of advanced breast cancer by increasing the anti-proliferative effect of NAP within the CSC subpopulation.
The functionality and reactivity of polysaccharides, and in particular hyaluronic acid, in combination with proteins like gelatin, collagen and many others, offer very interesting opportunities for the new trends in regenerative medicine. In this review is described the relevance of gelatin (Gel) and hyaluronic acid (HA) biopolymers in the field of tissue engineering due to the excellent response of these biomimetic materials and their bioactive and biodegradable character in the human body. In addition, it is reported an overview of the most relevant crosslinking processes and agents that are being developed for regenerative medicine, including different hydrogel modifications as well as several interesting and advanced applications. The growing of clinical applications of these macromolecular components as assemblies opens new and advanced opportunities in regenerative medicine and drug delivery fields.
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3729048 EZVWJRLR items 1 nature default asc 1 1 title1.Mora-Boza, A. et al. Contribution of bioactive hyaluronic acid and gelatin to regenerative medicine. Methodologies of gels preparation and advanced applications. European Polymer Journal 95, 11–26 (2017). Cite