Co-assembly of cisplatin and dasatinib in hyaluronan nanogel to combat triple negative breast cancer with reduced side effects.

Treatment for triple negative breast cancer (TNBC) remains a huge challenge due to the lack of targeted therapeutics and tumor heterogenicity. Cisplatin (Cis) have demonstrated favorable therapeutic response in TNBC and thus is used together with various kinase inhibitors to fight the heterogenicity of TNBC. The combination of Cis with SRC inhibitor dasatinib (DAS) has shown encouraging anti-TNBC efficacy although the additive toxicity was commonly observed. To overcome the severe side effects of this Cis involved therapy, here we co-encapsulated Cis and DAS into a self-assembled hyaluronan (HA) nanogel (designated as HA/Cis/DAS (HCD) nanogel) to afford the TNBC targeted delivery by using the 4T1 mouse model. The acquired HCD nanogel was around 181 nm in aqueous solution, demonstrating the pharmacological activities of both Cis and DAS. Taking advantages of HA's targeting capability towards CD44 that is overexpressed on many TNBC cells, the HCD could well maintain the anticancer efficacy of the Cis and DAS combination, significantly increase the maximum tolerated dose and relieve the renal toxicity in vivo. The current HCD nanogel provides a potent strategy to improve the therapeutic outcome of Cis and DAS combination and thus representing a new targeted treatment option for TNBC.

Flow behavior and linear viscoelasticity of cellulose 1-allyl-3-methylimidazolium formate solutions.

The rheological properties of α-cellulose 1-allyl-3-methylimidazolium formate solutions were investigated using shear viscosity and dynamic rheological measurements in a large range of concentrations (0.1-10 wt%) at 25 °C. In steady shear measurement, the overlap concentration (c*) and the entanglement concentration (c(e)) were determined to be 0.5 and 2.0 wt% respectively, and the exponents of the specific viscosity (η(sp)) versus the concentration (c) were determined as 1.0, 2.0 and 4.7 for dilute, semidilute unentangled and entangled regimes respectively, which were in accordance with the scaling prediction for neutral polymer in θ solvent. The slopes of the relaxation time (τ) against the concentration for semidilute unentangled and entangled regimes were observed as 1.0 and 2.5 respectively. In dilute and semidilute unentangled regimes, failure of the Cox-Merz rule with steady shear viscosity larger than complex viscosity was observed; while the deviation from the Cox-Merz rule disappeared in semidilute entangled regime.