Dual-crosslinked injectable in situ forming Alginate/CaCl2/Pluronic F127/α-Cyclodextrin hydrogels incorporating Doxorubicin and graphene-based nanomaterials for cancer chemo-photothermal therapy

Résumé fourni par la source

Injectable in situ forming hydrogels have been emerging due to their capacity to perform the direct delivery of therapeutics into the tumor site with minimal off-target leakage. Particularly, physical crosslinked injectable in situ forming hydrogels are appealing due to their straightforward preparation that exploits the native jointing capabilities of specific polymers/materials. However, the features of these hydrogels ( e.g. , injectability, degradation, swelling) are strongly pre-determined by the physical interactions available on the selected polymers/materials, occasionally yielding undesired outcomes. Thus, the combination of multiple physical crosslinking cues may allow the preparation of hydrogels with enhanced properties. In this work, a dual-crosslinked injectable in situ forming hydrogel was engineered by combining Pluronic F127/α-Cyclodextrin and Alginate/CaCl 2 ( i.e. , combination of host-guest and electrostatic interactions), being loaded with Doxorubicin (chemotherapeutic drug) and Dopamine-reduced Graphene Oxide (photothermal nano-agent) for application in cancer chemo-photothermal therapy. When compared to the single-crosslinked hydrogels, the dual-crosslinking contributed to the assembly of formulations with suitable injectability and improved degradation and water absorption behaviors. Moreover, the dual-crosslinked hydrogels presented a good photothermal capacity (ΔT ≈ 14 °C), leading to a 1.18-times enhanced Doxorubicin release. In in vitro cell-based studies, the dual-crosslinked hydrogels exhibited an excellent cytocompatibility towards healthy (normal human dermal fibroblasts) and breast cancer (MCF-7) cells. As importantly, the dual-crosslinked hydrogels were able to mediate a chemo-photothermal effect that diminished the cancer cells’ viability to just 23%. Overall, the developed dual-crosslinked injectable in situ forming hydrogels incorporating Doxorubicin and Dopamine-reduced Graphene Oxide are a promising macroscale system for breast cancer chemo-photothermal therapy.

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