Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer.

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.

Bioprinting a thick and cell-laden partially oxidized alginate-gelatin scaffold with embedded micro-channels as future soft tissue platform.

Despite all the advancements in tissue engineering, one of the unsolved challenges is the mass transfer limitation. Therefore, the subject of pre-vascularization in the engineered tissues gets more attention to avoid necrotic core formation. In this study, we considered a design for interconnected channels with a muscle tissue-like structure, in silico and in vitro. A sequence of simple steps make it possible for us to use the same material, gelatin, as both a sacrificial material and one of the main components of the scaffold simultaneously. We defined a new approach to quantify the repeatability of a new combination of hydrogels (Partially Oxidized Alginate + Gelatin) for extrusion-based bioprinting. Additionally, the mechanical properties, hydrogel porosity, degradation time, and swelling ratio were also evaluated. Based on all these test results, the scaffold with the optimum properties was chosen for the bioprinting of adipose derived mesenchymal stem cells (ADMSCs) in the scaffolds with and without the channels. This bioprinted scaffold with microchannels showed promising mimicry of the microenvironment, leading to higher survival and proliferation rates of the cells by up to 250%. Based on these results, it has the potential to serve as a platform for further research in vascularization, healthy/disease modelling, and stem cell differentiation.