Restoring joint homeostasis is crucial for relieving osteoarthritis (OA). Current strategies are limited to unilateral efforts in joint lubrication, inhibition of inflammation, free radicals scavenging, and cartilage regeneration. Herein, by modifying molybdenum disulfide (MoS2 ) with Mg2+ -doped polydopamine and coating with polysulfobetaines, we constructed a dual-bionic photothermal nanozyme (MPMP) to mimic antioxidases/hyaluronan synthase for OA therapy. Photothermally enhanced lubrication lowered the coefficient of friction (0.028) in the early stage of OA treatment. The antioxidases-mimicking properties of MPMP nanozyme contributed to eliminating ROS/RNS (over 90% of scavenging ratio for H2 O2 /·OH/O·-2/DPPH/ABTS+ ) and supplying O2 . With NIR irradiation, MPMP nanozyme triggered thermogenesis (upregulating HSP70 expression) and Mg2+ release, which promoted the chondrogenesis in inflammatory conditions by deactivating of NF-κB/IL-17 signaling pathways and enhancing MAPK signaling pathway. Benefiting from HSP70 and Mg2+ , MPMP-NIR showed HAS-mimicking activity to increase the intracellular (2.00-fold) and extracellular (3.12-fold) HA production. Therefore, MPMP-NIR demonstrated superior spatiotemporally therapeutic effect on OA in mice model, in terms of osteophytes (83.41% reduction), OARSI scores (88.57% reduction) and ACAN expression (2.70-fold increment). Hence, insights into dual-bionic nanozymes can be a promising strategy for OA therapy or other inflammation-related diseases. This article is protected by copyright. All rights reserved.

Mimicking Antioxidases And Hyaluronan Synthase: A Novel Zwitterionic Nanozyme for Photothermal Therapy of Osteoarthritis.

As a controllable, simple method with few side effects, near-infrared (NIR) light-based photothermal therapy (PTT) has been proven an effective cancer therapeutic approach. However, PTT-induced inflammation is a potential negative factor. And the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. In this work, small-size Ti3C2Tx MXene nanosheets with high photothermal conversion efficiency in the region of NIR, high cargo loading capability and good free radical scavenging capability were chosen for cancer PTT and anti-inflammation. And (-)-epigallocatechin gallate (EGCG) was applied to form EGCG/Fe metal-polyphenol nanodots on the nanosheets. EGCG being released in acid cancer cells could reduce the expression of HSPs and could be used for anti-inflammation. As a result, the complex nanosheets named MXene@EGCG could achieve enhanced cancer PTT and be anti-inflammatory. Both in vitro and in vivo studies proved the good photothermal ability of MXene@EGCG and demonstrated that it could inhibit the expression of HSPs in tumor cells and relieve PTT-induced inflammation. Therefore, the nanosheets show good results in tumor ablation with a low level of inflammation, which provides another possibility for cancer therapy. STATEMENT OF SIGNIFICANCE: : Photothermal therapy (PTT)-induced inflammation plays an essential role in some important stages of tumor development and is unfavorable for cancer treatment. And hyperthermia leads to the overexpression of heat shock proteins (HSPs) in cancer cells, which limits the therapeutic effect of PTT. Therefore, we coated small-size Ti3C2Tx MXene nanosheets with (-)-epigallocatechin gallate (EGCG)/Fe metal-polyphenol nanodots and named them as MXene@EGCG. This system shows a good photothermal conversion efficiency at 808 nm. And it can release EGCG in cancer cells to inhibit the expression of HSPs, thus achieving an enhanced cancer PTT. Both MXene and EGCG can also diminish the PTT-trigged inflammation. Both in vitro and in vivo studies prove the good anti-cancer PTT effect and anti-inflammation capability of MXene@EGCG.

Small-Size Ti3C2Tx MXene Nanosheets Coated with Metal-Polyphenol Nanodots for Enhanced Cancer Photothermal Therapy and Anti-Inflammation.

Preparation of epigallocatechin gallate decorated Au-Ag nano-heterostructures as NIR-sensitive nano-enzymes for the treatment of osteoarthritis through mitochondrial repair and cartilage protection.

The ongoing outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) pandemic has posed significant challenges in early viral diagnosis. Hence, it is urgently desirable to develop a rapid, inexpensive, and sensitive method to aid point‐of‐care SARS‐CoV‐2 detection. In this work, we report a highly sequence‐specific biosensor based on nanocomposites with aggregation‐induced emission luminogens (AIEgen)‐labeled oligonucleotide probes on graphene oxide nanosheets (AIEgen@GO) for one step‐detection of SARS‐CoV‐2‐specific nucleic acid sequences (Orf1ab or N genes). A dual “turn‐on” mechanism based on AIEgen@GO was established for viral nucleic acids detection. Here, the first‐stage fluorescence recovery was due to dissociation of the AIEgen from GO surface in the presence of target viral nucleic acid, and the second‐stage enhancement of AIE‐based fluorescent signal was due to the formation of a nucleic acid duplex to restrict the intramolecular rotation of the AIEgen. Furthermore, the feasibility of our platform for diagnostic application was demonstrated by detecting SARS‐CoV‐2 virus plasmids containing both Orf1ab and N genes with rapid detection around 1 h and good sensitivity at pM level without amplification. Our platform shows great promise in assisting the initial rapid detection of the SARS‐CoV‐2 nucleic acid sequence before utilizing quantitative reverse transcription‐polymerase chain reaction for second confirmation.

An AIEgen/graphene oxide nanocomposite (AIEgen@GO)‐based two‐stage “turn‐on” nucleic acid biosensor for rapid detection of SARS‐CoV‐2 viral sequence

The transfer of the concept of chirality from molecules to synthesized nanomaterials has attracted attention amongst multidisciplinary teams. Here we demonstrate heterogeneous nucleation and anisotropic accumulation of Au nanoparticles on multilayer MoS2 planes to form chiroptically functional nanomaterials. Thiol amino acids with chiral conformations modulate asymmetric growth of gold nanoarchitectures on seeds of highly faceted Au/MoS2 heterostructures. Consequently, dendritic plasmonic nanocrystals with partial chiral morphologies are synthesized. The chirality of dendritic nanocrystals inherited from cysteine molecules refers to the structural characteristics and includes specific recognition of enantiomeric molecules. With integration of the intrinsic photothermal properties and inherited enantioselective characteristics, dendritic Au/MoS2 heterostructures exhibit chirality-dependent release of antimicrobial drugs from hydrogel substrates when activated by exogenous infrared irradiation. A three-in-one strategy involving synthesis of chiral dendritic heterostructures, enantioselective recognition, and controlled drug release system is presented, which improves nanomaterial synthetic technology and enhances our understanding of crucial chirality information. 

/pdf/chiral-nanocrystals-grown-from-mos2-nanosheets-enable-1qgl49po.pdf

Chiral nanocrystals grown from MoS2 nanosheets enable photothermally modulated enantioselective release of antimicrobial drugs

Osteoarthritis (OA) is a leading cause of chronic pain in the elderly worldwide. Yet current diagnosis and therapy for OA pain are subjective and nonspecific with significant adverse effects. Here, we introduced a theranostic nanoprobe based on molybdenum disulfide nanosheet-coated gold nanorods (MoS2-AuNR) targeting never growth factor (NGF), a key player in pain sensation, for photoacoustic pain imaging and near-infrared (NIR) imaging-guided photothermal analgesic therapy. MoS2 coating significantly improved the photoacoustic and photothermal performance of AuNR. Functionalization of MoS2-AuNR nanoprobes by conjugating with NGF antibody enabled active targeting on painful OA knees in a surgical OA murine model. We observed that our functional nanoprobes accumulated in the OA knee rather than the contralateral intact one, and the amount was correlated with the severity of mechanical allodynia in our mouse model. Under imaging guidance, NIR-excited photothermal therapy could mitigate mechanical allodynia and walking imbalance behavior for both subacute and chronic stages of OA in a preclinical setting. This molecular theranostic approach enabled us to specifically localize the source of OA pain and efficiently block peripheral pain transmission.

Nerve Growth Factor-Targeted Molecular Theranostics Based on Molybdenum Disulfide Nanosheet-Coated Gold Nanorods (MoS2-AuNR) for Osteoarthritis Pain.

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Nerve Growth Factor-Targeted Molecular Theranostics Based on Molybdenum Disulfide Nanosheet-Coated Gold Nanorods (MoS2-AuNR) for Osteoarthritis Pain.