Tumor vascular heterogeneity and the impact of subtumoral nanoemulsion biodistribution.

Aim: Investigate the heterogeneous tumor tissue organization and examine how this condition can interfere with the passive delivery of a lipid nanoemulsion in two breast cancer preclinical models (4T1 and Ehrlich). Materials & methods: The authors used in vivo image techniques to follow the nanoemulsion biodistribution and microtomography, as well as traditional histopathology and electron microscopy to evaluate the tumor structural characteristics. Results & conclusion: Lipid nanoemulsion was delivered to the tumor, vascular organization depends upon the subtumoral localization and this heterogeneous organization promotes a nanoemulsion biodistribution to the highly vascular peripherical region. Also, the results are presented with a comprehensive mathematical model, describing the differential biodistribution in two different breast cancer models, the 4T1 and Ehrlich models.

Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant.

Metal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFe2O4 NPs were synthesized by co-precipitation and evaluated by transmission electron microscopy. The vaccine was formulated by homogenizing NPs with the recombinant protein, and protein corona formation was determined by dynamic light scattering and field-emission scanning electron microscopy. The vaccine was evaluated for the best immunization route and strategy using subcutaneous and intranasal routes with 21-day intervals between immunizations. When administered subcutaneously, the vaccine generated specific CD4+IFN-γ+ (Th1) and CD8+IFN-γ+ responses. Intranasal vaccination induced specific Th1, Th17 (CD4+IL-17+) and Tc1 responses, mainly in the lungs. Finally, a mixed vaccination strategy (2 subcutaneous injections followed by one intranasal vaccination) induced a Th1 (in the spleen and lungs) and splenic Tc1 response but was not capable of inducing a Th17 response in the lungs. This study shows for the first time a subunit vaccine with iron oxide based NPs as an adjuvant that generated cellular immune responses (Th1, Th17 and TCD8), thereby exhibiting good adjuvant qualities. Additionally, the immune response generated by the subcutaneous administration of the vaccine diminished the bacterial load of Mtb challenged animals, showing the potential for further improvement as a vaccine against tuberculosis.