Immunostimulatory lipogel implant enhances cancer immunotherapy
Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt d'un lipogel permettant de délivrer au niveau de la tumeur de l'acide tout-trans rétinoïque et de la doxorubicine pour déclencher une réponse immunitaire antitumorale via la mort immunogène des cellules souches cancéreuses, prévenir le risque de récidive postchirurgicale et supprimer, en combinaison avec un inhibiteur de point de contrôle immunitaire, la croissance tumorale ainsi que le développement de métastases
Cancer stem-like cells contribute to innate tumour immunoresistance and an immunosuppressive tumour microenvironment, leading to poor responses to immune checkpoint inhibitors. Chemotherapeutic agents can elicit tumour immunogenicity by inducing immunogenic cell death to reinforce the therapeutic efficacies of immune checkpoint inhibitors, but suffer from inefficient immunogenic cell death activation in highly resistant cancer stem-like cells. Here we report an immunostimulatory lyotropic liquid-crystal-based lipogel for localized co-delivery of all-trans retinoic acid, a differentiation-inducing drug, and doxorubicin, an immunogenic-cell-death-inducing chemotherapeutic agent with distinct release kinetics. The lipogel is tailored to release the combinatorial drugs in a differential and sustained manner, which fulfils the requirement for enhanced drug synergism in promoting the immunogenic cell death of cancer stem-like cells. Local implantation of the immunostimulatory lipogel elicits an antitumour immune response that is further augmented by an immune checkpoint inhibitor to suppress tumour growth and metastasis, as well as to prevent post-surgical recurrence in murine models of high-stemness tumours.
Nature Nanotechnology , article en libre accès, 2026