Immunoinducible Carbon Dot-Incorporated Hydrogels as a Photothermal-Derived Antigen Depot to Trigger a Robust Antitumor Immune Response.

Immunogenic tumor cell death (ICD) induced by photothermal therapy (PTT) fails to elicit a robust antitumor immune response partially due to its inherent immunosuppressive microenvironment and poor antigen presentation. To address these issues, we developed an immunoinducible carbon dot-incorporated hydrogel (iCD@Gel) through a dynamic covalent Schiff base reaction using mannose-modified aluminum-doped carbon dots (M/A-CDs) as a cross-linking agent. The M/A-CDs possessed superior photothermal conversion efficiency and served as nanocarriers to load cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) for inducing the maturation of dendritic cells (DCs) via mannose receptor-mediated targeting delivery. Upon intratumoral injection, the as-prepared iCD@Gel induced ICD, and damage-associated molecular patterns (DAMPs) were released via photothermal ablation under 808 nm NIR irradiation. Subsequently, the iCD@Gel synergized with the DAMPs to significantly promote the maturation and antigen cross-presentation ability of DCs. This work provides a promising strategy to develop carbon dot-based therapeutic hydrogels for photothermal therapy and immune activation.

Calcium and phosphorus co-doped carbon dots enhance osteogenic differentiation for calvarial defect repairin situ.

Calvarial bone defect remains a clinical challenge due to the lack of efficient osteo-inductive agent. Herein, a novel calcium and phosphorus codoped carbon dot (Ca/P-CD) for bone regeneration was synthesized using phosphoethanolamine and calcium gluconate as precursors. The resultant Ca/P-CDs exhibited ultra-small size, stable excitation dependent emission spectra and favorable dispersibility in water. Moreover, Ca/P-CDs with good biocompatibility rapidly entered the cytoplasm through endocytosis and increased the expression of bone differentiation genes. After mixing with temperature-sensitive hydrogel, Ca/P-CDs were injectedin situinto calvarial defect and promoted the repair of bone injury. These Ca/P-CDs provide a new treatment method for the bone repair and should be expended the application in the biomedical fields.

Fabrication of methylene blue-loaded ovalbumin/polypyrrole nanoparticles for enhanced phototherapy-triggered antitumour immune activation.

BACKGROUND: Phototherapy-triggered immunogenic cell death (ICD) rarely elicits a robust antitumour immune response, partially due to low antigen exposure and inefficient antigen presentation. To address these issues, we developed novel methylene blue-loaded ovalbumin/polypyrrole nanoparticles (MB@OVA/PPY NPs) via oxidative polymerization and π-π stacking interactions. RESULTS: The as-prepared MB@OVA/PPY NPs with outstanding photothermal conversion efficiency (38%) and photodynamic properties were readily internalized into the cytoplasm and accumulated in the lysosomes and mitochondria. Upon 808 nm and 660 nm laser irradiation, the MB@OVA/PPY NPs not only ablated tumour cells by inducing local hyperthermia but also damaged residual tumour cells by generating a large amount of reactive oxygen species (ROS), finally triggering the release of many damage-associated molecular patterns (DAMPs). Moreover, the MB@OVA/PPY NPs synergized with DAMPs to promote the maturation and improve the antigen presentation ability of DCs in vitro and in vivo. CONCLUSIONS: This work reported a PPY NPs-based nanoplatform to encapsulate the therepeutic proteins and absorb the functional molecules for combination therapy of tumours. The results demonstrated that the prepared MB@OVA/PPY NPs could be used as effective nanotherapeutic agents to eliminate solid tumours and trigger a powerful antitumour immune response.