Abstract
Immunological adjuvants are essential for successful cancer vaccination. However, traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. Here, we present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. Under irradiation with near-infrared light, the LIA not only induces tumour cell lysis and tumour antigen release, but also promotes the structural transformation of 2-nitroimidazole containing dendrimer to 2-aminoimidazole containing dendrimer which can activate dendritic cells via the Toll-like receptor 7-mediated signaling pathway. The LIA efficiently inhibits both primary and abscopal tumour growth and induces strong antigen-specific immune memory effect to prevent tumour metastasis and recurrence in vivo. Furthermore, LIA localizes the immunological adjuvant effect at the tumour site. We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination.
Highlights
Immunological adjuvants are essential for successful cancer vaccination
In order to investigate if the adjuvant effect is light-activable immunological adjuvant (LIA)-specific, we evaluated the activation of Bone marrowderived dendritic cells (BMDCs) after free chlorin e6 (Ce6) or DP-Ce6 (Ce6 encapsulated in DSPEPEG2000) nanoparticle treatment
To understand the mechanism of the immunological adjuvant effect of LIA after irradiation, we evaluated the transcriptomic features of the BMDCs treated with hypoxia-responsive amphiphilic dendrimer (HAD) and rHAD
Summary
Immunological adjuvants are essential for successful cancer vaccination. traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. We present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. LIA localizes the immunological adjuvant effect at the tumour site We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination. Various types of adjuvants have been developed, including mineral salts, microorganism-derived adjuvants and nucleic acid-based adjuvants[19,20] These adjuvants without controllability may enter into the circulation and induce severe toxicities which restrict the broad application of cancer vaccines[21,22]. We present a light-activable immunological adjuvant (LIA), composed of a hypoxia-responsive amphiphilic dendrimer (HAD) nanoparticle loaded with a photodynamic agent, chlorin e6 (Ce6). All results verify that the light-activable immunological adjuvant mediates a safe and robust in situ vaccination against tumours
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