Dendrimers as Color-Stabilizers of Pyranoanthocyanins: the Dye Concentration Governs the Host-Guest Interaction Mechanisms

Anionic dendrimers have recently emerged as hosts (H) for the color stabilization of the flavylium cation of anthocyanin guests (G). The interaction with a promising, more hydrophobic pyranoanthocyanin illustrates how the structure and concentration of the dye modulate the host–guest interaction mechanisms. NMR and UV–vis titrations (host over guest, from G/H ratio 2089 to 45) showed that at relatively low dendrimer-to-dye concentrations, ion pairs at the dendrimer periphery prevail over dye encapsulation. This promotes the deaggregation of the dye, not previously observed with anthocyanins, and related to the more hydrophobic nature of this dye (deshielding of the dye 1H signals, higher T2 relaxation times, constant diffusion coefficient). As the dendrimer concentration increases, the dye encapsulation, earlier unseen with structurally simpler flavylium dyes, becomes dominant (shielding and broadening of the dye 1H signals and lower T2 and diffusion coefficient). The interaction parameters of the encapsulation process (K ∼ 4.51 × 104 M–1, n ∼ 150) indicate the binding of ca. one pyranoanthocyanin molecule by each sulfate terminal group. Our results provide insights into the ability of dendrimers to host structurally diverse pyranoflavylium-based dyes and how the structure of the latter modulates the range of interactions involved. The encapsulation ability of this dendrimer to such pH-sensitive dyes is envisioned for the host–guest sensing applications such as pH-responsive systems used for example in food smart packagingThis research was supported by a research project grant (PTDC/OCE-ETA/31250/2017) with financial support from FCT/MCTES through national funds and co-financed by FEDER, under the Partnership Agreement PT2020 (UID/QUI/50006/2020, ). This research was conducted under the project AgriFood XXI–NORTE-01–0145-FEDER-000041, financed by European Regional Development Fund (FEDER) through North Portugal Regional Operational Programme (Norte 2020). Financial support was also obtained from the Spanish Ministry of Science and Innovation (RTI2018-102212-B-I00), Xunta de Galicia (ED431C 2018/30 and Centro singular de investigación de Galicia accreditation 2019–2022, ED431G 2019/03), Axencia Galega de Innovación (IN845D 2020/09), and the European Union (European Regional Development Fund-ERDF)S

Mannose-modified hyaluronic acid nanocapsules for the targeting of tumor-associated macrophages

Tumor-associated macrophages (TAMs), a class of immune cells that play a key role in tumor immunosuppression, are recognized as important targets to improve cancer prognosis and treatment. Consequently, the engineering of drug delivery nanocarriers that can reach TAMs has acquired special relevance. This work describes the development and biological evaluation of a panel of hyaluronic acid (HA) nanocapsules (NCs), with different compositions and prepared by different techniques, designed to target macrophages. The results showed that plain HA NCs did not significantly influence the polarization of M0 and M2-like macrophages towards an M1-like pro-inflammatory phenotype; however, the chemical functionalization of HA with mannose (HA-Man) led to a significant increase of NCs uptake by M2 macrophages in vitro and to an improved biodistribution in a MN/MNCA1 fibrosarcoma mouse model with high infiltration of TAMs. These functionalized HA-Man NCs showed a higher accumulation in the tumor compared to non-modified HA NCs. Finally, the pre-administration of the liposomal liver occupying agent Nanoprimer™ further increased the accumulation of the HA-Man NCs in the tumor. This work highlights the promise shown by the HA-Man NCs to target TAMs and thus provides new options for the development of nanomedicine and immunotherapy-based cancer treatmentsOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the 2^2-INTRATARGET project (A20/00028) funded by the ISCIII under the umbrella of the ERA NET EuroNanoMed GA N 723770 of the EU Horizon 2020 Research and Innovation Programme. This work was also supported by the Xunta de Galicia (ED431C 2018/30, and “Centro singular de investigación de Galicia” accreditation 2019 − 2022, ED431G2019/03), and the European Union (European Regional Development Fund-ERDF)S