Multifunctional STING-Activating Mn3 O4 @Au-dsDNA/DOX Nanoparticle for Antitumor Immunotherapy.

The promise of immunotherapy for cancer therapy has not been fully fulfilled because portions of tumors are immunosuppressive. To tackle this challenge, the initiation of immune system by stimulator of interferon genes (STING) pathway is explored and multifunctional STING-activating nanoparticles are rationally designed for synergistic antitumor therapy. The STING-activating nanoparticles have a formulation of Mn3 O4 @Au-dsDNA/DOX, where dsDNA is used to activate STING for immunotherapy and doxorubicin (DOX) is chosen as a model drug for chemotherapy. The STING-mediated immunity is activated, inducing interferon-ß (IFN-ß) production, increasing T cell priming, and enhancing effector T cell infiltration. Combined with chemotherapy, STING-mediated immunotherapy shows good antitumor efficacy by inhibiting tumor growth and prolonging survival rate in vivo. The promise of cancer immunotherapy can be fulfilled by combining novel antitumor immunity with innovative nanotechnology, and chemotherapy and targeted therapies.

N-Doped Carbon As Peroxidase-Like Nanozymes for Total Antioxidant Capacity Assay.

N-doping strategy has been explored to enhance the activity of carbon nanozymes because the reconstructed electronic structures in N-doped carbon nanozymes are advantageous for the catalytic process. However, carbon nanozymes with high N content are still difficult to obtain due to the instability of N element under high calcination temperatures. To address this challenge, here we proposed a new N-doping strategy to fabricate highly active and specific peroxidase-like carbon nanozymes by using a high N-containing polymer (i.e., polyethylenimine (PEI)) as the N source and a natural clay mineral (i.e., montmorillonite (MMT)) as a template, respectively. We showed that the assembly of MMT with PEI protected N loss under high calcination temperatures and thus retained more catalytically active N sites. The mechanism study showed that the hydroxyl radical could be the key intermediate involved in the peroxidase-like catalysis. We then used the optimized carbon nanozyme with high and specific peroxidase-like activity (i.e., CP600-6) to detect H2O2, glucose, and ascorbic acid. Moreover, we successfully determined the total antioxidant capacity (TAC) in real samples including four commercial beverages, fresh orange juice, and three kinds of vitamin C tablets. The current study not only provides a new strategy for fabricating peroxidase-like nanozymes but also develops a facile TAC assay for future use in evaluation of antioxidant food quality and oxidative stress in healthcare.

Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II).

Nanozymes are nanomaterials with enzyme-like characteristics (Chem. Soc. Rev., 2013, 42, 6060-6093). They have been developed to address the limitations of natural enzymes and conventional artificial enzymes. Along with the significant advances in nanotechnology, biotechnology, catalysis science, and computational design, great progress has been achieved in the field of nanozymes since the publication of the above-mentioned comprehensive review in 2013. To highlight these achievements, this review first discusses the types of nanozymes and their representative nanomaterials, together with the corresponding catalytic mechanisms whenever available. Then, it summarizes various strategies for modulating the activity and selectivity of nanozymes. After that, the broad applications from biomedical analysis and imaging to theranostics and environmental protection are covered. Finally, the current challenges faced by nanozymes are outlined and the future directions for advancing nanozyme research are suggested. The current review can help researchers know well the current status of nanozymes and may catalyze breakthroughs in this field.

Nanozyme Sensor Arrays for Detecting Versatile Analytes from Small Molecules to Proteins and Cells.

Nanozymes have emerged as promising alternatives to overcome the high cost and low stability of natural enzymes. Nanozymes with peroxidase-like activities have been studied to construct versatile biosensors by using specific biorecognition ligands (such as enzymes, antibodies, and aptamers) or molecularly imprinted polymers (MIPs). However, the use of bioligands compromises the high stability and low cost promise of nanozymes, while the MIPs may not be applicable to multiplex detection. To address these limitations, here we constructed the nanozyme sensor arrays based on peroxidase-like Pt, Ru, and Ir nanozymes. The cross-reactive nanozyme sensor arrays were successfully used for the detection of biothiols and proteins as well as the discrimination of cancer cells because of the differential nonspecific interactions between the components of the sensor arrays and the analytes. The usefulness of the nanozyme sensor arrays was further validated by the detection of blind unknown samples, where 28 of 30 biothiols and 42 of 45 proteins were correctly identified. Moreover, the practical application of the nanozyme sensor arrays was demonstrated by the successful discrimination of biothiols in serum and proteins in human urine.

Acid Susceptible Ultrathin Mesoporous Silica Coated on Layered Double Hydroxide Nanoplates for pH Responsive Cancer Therapy.

Bioresponsive drug delivery systems that can modulate drug release profiles according to different tumor microenvironment are highly desired for improving cancer therapy. In this work, a pH-responsive nanocarrier, layered double hydroxide (LDH) nanoplates coated with ultrathin mesoporous silica layer (LDH@MS), was fabricated with total thickness of around 9 nm. The coating of ultrathin porous silica significantly improved the stability of nanoplates. Moreover, the LDH@MS exhibited pH responsive functionality due to the degradation of silica shell and LDH under moderately acidic pH condition. Notably, the curcumin loaded LDH@MS displayed nearly five-fold greater antitumor efficacy against human breast cancer cells in vitro and marked tumor inhibition in vivo compared to free curcumin under the same drug dosage, most likely due to high dispersibility of the nanocarrier, as well as responsive and steady release of drug molecules. This study opens new avenues to design safer and more effective drug delivery systems with improved therapeutic outcomes.