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.

Impact of different organic matters on the occurrence of antibiotic resistance genes in activated sludge.

The occurrence of antibiotic resistance genes (ARGs) in various environments has drawn worldwide attention due to their potential risks. Previous studies have reported that a variety of substances can enhance the occurrence and dissemination of ARGs. However, few studies have compared the response of ARGs under the stress of different organic matters in biological wastewater treatment systems. In this study, seven organic pollutants were added into wastewater treatment bioreactors to investigate their impacts on the ARG occurrence in activated sludge. Based on high-throughput sequencing, it was found that the microbial communities and ARG patterns were significantly changed in the activated sludge exposed to these organic pollutants. Compared with the non-antibiotic refractory organic matters, antibiotics not only increased the abundance of ARGs but also significantly changed the ARG compositions. The increase of Gram-negative bacteria (e.g., Archangium, Prosthecobacter and Dokdonella) carrying ARGs could be the main cause of ARG proliferation. In addition, significant co-occurrence relationships between ARGs and mobile genetic elements were also observed in the sludge samples, which may also affect the ARG diversity and abundance during the organic matter treatment in the bioreactors. Overall, these findings provide new information for better understanding the ARG occurrence and dissemination caused by organic pollutants in wastewater treatment systems.

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.

Curcumin doped zeolitic imidazolate framework nanoplatforms as multifunctional nanocarriers for tumor chemo/immunotherapy.

Curcumin as a hydrophobic polyphenol has great potential for tumor therapy, yet its rapid degradation and hydrophobicity severely impair its therapeutic effect in the clinic. Herein, we report a novel strategy for the formation of curcumin doped zeolitic imidazolate framework nanoparticles (Cur-ZIF NPs) by zinc ion driven simultaneous coordination of curcumin and 2-methylimidazole. The resultant Cur-ZIF NPs with a uniform nanosize exhibit favorable stability and dispersibility in water, as well as high drug-loading capacities. The pH and redox sensitivity of ZIF NPs enable the controlled release of curcumin in vivo. Moreover, Cur-ZIF NPs serve as nanocarriers that can load the toll-like-receptor-7 agonist (imiquimod, IQ) and be coated by homotypic cancer cell membranes to enhance tumor-targeted delivery. This study provides an attractive nanoplatform to effectively utilize curcumin and integrate multiple therapeutic modalities into a single system for tumor treatment.

NIR responsive tumor vaccine in situ for photothermal ablation and chemotherapy to trigger robust antitumor immune responses.

BACKGROUND: Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. RESULTS: HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. CONCLUSION: Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

Mussel-inspired in situ fabrication of a photothermal composite hydrogel for MR-guided localized tumor ablation.

Photothermal ablation could be considered an effective treatment for tumors, but accurate administration and enrichment of photothermal agents remain a huge challenge. Herein, a mussel-inspired photothermal polymeric hydrogel (PPH) was synthesized through a ferric iron-triggered simultaneous metal-catechol coordination reaction and oxidative polymerization of covalently linked pyrrole. The PPH with rapid gelation (less than 10 s) exhibited high photothermal conversion efficiency (49.3%), which enabled effective hyperthermal therapy in situ. Besides, the introduced iron could be used as a T 2-weighted contrast agent for real-time MR imaging to explore the retention and bio-degradation of PPH in vivo. Overall, our findings evidence that the resultant PPH, which possesses potential application in tumor ablation in situ, and metal-catechol coordination strategy inspired by mussel adhesion may stimulate biomedical hydrogel development.