A photo-inducible protein-inorganic nanoparticle assembly for active targeted tumour theranostics.

The assembly of protein-inorganic nanoparticles is an important yet challenging approach that is utilized to develop functional materials in numerous areas, such as bio-catalysis, drug delivery, and biosensing. In this study, we report on a facile, photo-inducible self-assembly method to generate protein-inorganic hybrid nanoplatforms. More specifically, photo-treated disulfide bond rich proteins of lysozyme (LYS) were able to be used as host materials in order to encapsulate nanoparticles (i.e., as-synthesized hydrophobic NIR quantum dots (QDs)) and anti-cancer small molecule drugs (i.e., paclitaxel (PTX)), constructing functional theranostic protein-inorganic hybrid nanoparticles. The modification of the functional polymer of cRGD-PEG contributes to the active tumour targeting characteristic of this protein-inorganic nanocarrier. This novel PTX loaded protein-inorganic hybrid nanoplatform showed high tumour homing accumulation as well as effective tumour inhibition. We believe that this general approach represents a new direction for the development of a photo-induced assembly of protein-inorganic nanoparticles towards versatile applications in both materials science and biomedical fields.

Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia.

T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution.