Self-assembling Collagen/Alginate hybrid hydrogels for combinatorial photothermal and immuno tumor therapy

Abstract Combination therapy, integrating multiple merits of monotherapy into one platform for enhanced antitumor efficacy while eliminating the likelihoods of tumor recurrence and metastasis, is of particular interest in clinical application. Hydrogels self-assembled by biologically-based building blocks can be used as promising platforms for incorporation of one or more therapeutic drugs to gain additive or synergistic therapeutic functions. Herein, antitumor combination therapy based on injectable collagen/alginate hydrogels is achieved by simultaneous encapsulation of the photothermal drug methylene blue (MB) and immunological agent imiquimod (R837). The resulting hybrid hydrogel (Gel-MB-R837) with shear-thinning and self-healing properties is applicable for localized delivery and prolonged release of therapeutic drugs. The antitumor efficacy can be significantly enhanced by combinatorial photothermal therapy (PTT) and immunotherapy treatments through the synergy of MB and R837. Moreover, the initial PTT not only eradicates primary tumors, but also generates tumor-associated antigens (TAA), which combines with R837 to trigger immune response for further inhibiting tumor recurrence and metastasis. Therefore, the biocompatible hybrid hydrogels starting from naturally-occurring biomacromolecules offer promising prospects for combinatorial photothermal and immuno tumor therapy.

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