Targosomes: Anti-HER2 PLGA nanocarriers for bioimaging, chemotherapy and local photothermal treatment of tumors and remote metastases.

Developing combined cancer therapy strategies is of utmost importance as it can enhance treatment efficacy, overcome drug resistance, and ultimately improve patient outcomes by targeting multiple pathways and mechanisms involved in cancer growth and progression. Specifically, the potential of developing a combination chemo&photothermal therapy using targeted polymer nanoparticles as nanocarriers offers a promising approach for synergistic cancer treatment by combining the benefits of both therapies, such as targeted drug delivery and localized hyperthermia. Here, we report the first targeted anti-HER2 PLGA nanocarriers, called targosomes, that simultaneously possess photothermal, chemotherapeutic and diagnostic properties using only molecular payloads. Biocompatible poly(lactic-co-glycolic acid), PLGA, nanoparticles were loaded with photosensitizer phthalocyanine, diagnostic dye Nile Blue, and chemotherapeutic drug irinotecan, which was chosen as a result of screening a panel of theragnostic nanoparticles. The targeted delivery to cell surface oncomarker HER2 was ensured by nanoparticle modification with the anti-HER2 monoclonal antibody, trastuzumab, using the one-pot synthesis method without chemical conjugation. The irradiation tests revealed prominent photothermal properties of nanoparticles, namely heating by 35 °C in 10 min. Nanoparticles exhibited a 7-fold increase in binding and nearly an 18-fold increase in cytotoxicity for HER2-overexpressing cells compared to cells lacking HER2 expression. This enhancement of cytotoxicity was further amplified by >20-fold under NIR light irradiation. In vivo studies proved the efficacy of nanoparticles for bioimaging of primary tumor and metastasis sites and demonstrated 93% tumor growth inhibition, making these nanoparticles excellent candidates for translation into theragnostic applications.

Crystal structure and electronic properties of low-dimensional hexamethylenediaminium lead halide perovskites.

This work reports on hybrid hexamethylenediaminium lead halide perovskites. The materials were prepared using wet synthesis and the subsequent precipitation from aqueous solution. Structural and morphological charactarization studies show their high degree of crystallinity and phase purity. The determined perovskites' structural parameters agree well with the literature reports. The recorded XPS and DRS data allowed for the first schematic representation of the perovskite band structures. The latter match well the results of DFT modeling. It is shown for the first time that the increase in the perovskite bandgaps is solely due to the increase in the anion electronegativity. Namely, as the anion electronegativity increases, the corresponding valence band energy decreases. In contrast, the electronegativity of the anions has no effect on the perovskite conduction band energies. The presented study deepens our understanding of the relationship between the crystal and electronic structures of low-dimensional hybrid halide perovskites.