Fullerene Rosette: Two-Dimensional Interactive Nanoarchitectonics and Selective Vapor Sensing.

The simplicity of fullerenes as assembled components provides attractive opportunities for basic understanding in self-assembly research. We applied in situ reactive methods to the self-assembly process of C60 molecules with melamine/ethylenediamine components in solution, resulting in a novel type of fullerene assemblies, micron-sized two-dimensional, amorphous shape-regular objects, fullerene rosettes. ATR−FTIR spectra, XPS, and TGA results suggest that the melamine/ethylenediamine components strongly interact and/or are covalently linked with fullerenes in the fullerene rosettes. The broad peak for layer spacing in the XRD patterns of the fullerene rosettes corresponds roughly to the interdigitated fullerene bilayer or monolayer of modified fullerene molecules. The fullerene rosettes are made from the accumulation of bilayer/monolayer assemblies of hybridized fullerenes in low crystallinity. Prototype sensor systems were fabricated upon immobilization of the fullerene rosettes onto surfaces of a quartz crystal microbalance (QCM), and selective sensing of formic acid was demonstrated as preliminary results for social-demanded toxic material sensing. The QCM sensor with fullerene rosette is categorized as one of the large-response sensors among reported examples. In selectivity to formic acids against basic guests (formic acid/pyridine >30) or aromatic guests (formic acid/toluene >110), the fullerene rosette-based QCM sensor also showed superior performance.

Nanomaterials and their composite scaffolds for photothermal therapy and tissue engineering applications.

Photothermal therapy (PTT) has attracted broad attention as a promising method for cancer therapy with less severe side effects than conventional radiation therapy, chemotherapy and surgical resection. PTT relies on the photoconversion capacity of photothermal agents (PTAs), and a wide variety of nanomaterials have been employed as PTAs for cancer therapy due to their excellent photothermal properties. The PTAs are systematically or locally administered and become enriched in cancer cells to increase ablation efficiency. In recent years, PTAs and three-dimensional scaffolds have been hybridized to realize the local delivery of PTAs for the repeated ablation of cancer cells. Meanwhile, the composite scaffolds can stimulate the reconstruction and regeneration of the functional tissues and organs after ablation of cancer cells. A variety of composite scaffolds of photothermal nanomaterials have been prepared to combine the advantages of different modalities to maximize their therapeutic efficacy with minimal side effects. The synergistic effects make the composite scaffolds attractive for biomedical applications. This review summarizes these latest advances and discusses the future prospects.

Bay11-7082 facilitates wound healing by antagonizing mechanical injury- and TNF-α-induced expression of MMPs in posterior cruciate ligament.

Purposes: To investigate the ability of synoviocytes (SCs) in regulating MMPs expression in the posterior cruciate ligament fibroblasts (PCLfs) after TNF-α treatment, to test whether a specific inflammation inhibitor Bay11-7082 can antagonize the expression of MMPs in PCLfs after injury. Methods: The microenvironment of knee joint cavity after PCL injury was mimicked in an in vitro co-culture system. The effects of TNF-α treatment on the expression of MMPs in PCL fibroblasts (PCLfs) were studied. The expression of MMPs mRNA and protein was detected by qRT-PCR and western blot. For the in vivo study, the Bay11-7082 inhibitor was injected into the knee joint cavity after injury, and then were performed on histological analysis. Results: In the mono-culture conditions, 6% mechanical injury upregulated the expression of MMP-2, whereas downregulated MMP-1 and -3, additionally 12% mechanical injury were upregulated all. However, in co-culture conditions, 6% and 12% both significantly increased MMPs expressions. Stretch injury and TNF-α treatment significantly upregulated expression of MMPs mRNA and protein levels in mono-cultured PCLfs. This effect was more significant in PCLfs Plus SCs co-culture system, in which the cells were treated by combination of stretch injury and TNF-α. In addition, Bay11-7082, a specific inflammation inhibitor, could significantly decrease the expression of MMPs induced by stretch injury and/or TNF-α treatment. Less infiltrated inflammatory cells and more integrated tissues were detected in injury PCL 2 weeks after Bay11-7082 treatment, compared to injury group. Immunofluorescent staining showed very low expression levels of MMPs in PCL of Bay11-7082-treated group, compared to the injury groups. Conclusions: SCs sever as the supporting cells that aggravate the TNF-α-induced MMPs accumulation in PCLfs. Inhibition of the expression of MMPs by Bay11-7082 is a promising way to facilitate the self-healing of PCL.

Oxygen-carrying semiconducting polymer nanoprodrugs induce sono-pyroptosis for deep-tissue tumor treatment.

Sonodynamic therapy (SDT) has been explored for cancer therapy, especially for deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited due to the complicated tumor microenvironment. This study reports the construction of oxygen-carrying semiconducting polymer nanoprodrugs (OSPNpro) for deep tumor treatment via combining amplified SDT with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic semiconducting polymer as the sonosensitizer, and reactive oxygen species (ROS)-responsive prodrug are co-loaded into a nanoparticle system, leading to the formation of these polymer nanoprodrugs. Such OSPNpro show an effective accumulation in tumor tissues after systemic administration, in which they deliver oxygen to relieve tumor hypoxia microenvironment and thus mediate amplified SDT via producing ROS under ultrasound (US) irradiation, even when the tumors are covered with a 2-cm chicken breast tissue. In addition, the ROS-responsive prodrugs are activated by the generated ROS to trigger pyroptosis of tumor cells. Such a sono-pyroptosis induces a strong antitumor immunity with obviously higher level infiltrations of effector immune cells into tumors. Therefore, OSPNpro-based combinational therapy can greatly inhibit the growth of 2-cm chicken breast tissue-covered deep tumors and suppress tumor metastasis. This study offers a prodrug nanoplatform for treatment of deep tumor via sono-pyroptosis strategy.

Rare-earth hydroxide/MXene hybrid: a promising agent for near-infrared photothermy and magnetic resonance imaging.

Layered gadolinium hydroxide (LGdH) and Ti3C2 monolayers were assembled into a LGdH/Ti3C2 (GTC) hybrid. The hybrid demonstrated enhanced near-infrared (NIR) light absorption properties and superior photothermal performance. Moreover, the GTC hybrid achieved an excellent T1-weighted magnetic resonance imaging (MRI) effect.

Three-dimensional culture and chondrogenic differentiation of mesenchymal stem cells in interconnected collagen scaffolds.

Interconnected scaffolds are useful for promoting the chondrogenic differentiation of stem cells. Collagen scaffolds with interconnected pore structures were fabricated with poly(lactic acid-co-glycolic acid) (PLGA) sponge templates. The PLGA-templated collagen scaffolds were used to culture human bone marrow-derived mesenchymal stem cells (hMSCs) to investigate their promotive effect on the chondrogenic differentiation of hMSCs. The cells adhered to the scaffolds with a homogeneous distribution and proliferated with culture time. The expression of chondrogenesis-related genes was upregulated, and abundant cartilaginous matrices were detected. After subcutaneous implantation, the PLGA-templated collagen scaffolds further enhanced the production of cartilaginous matrices and the mechanical properties of the implants. The good interconnectivity of the PLGA-templated collagen scaffolds promoted chondrogenic differentiation. In particular, the collagen scaffolds prepared with large pore-bearing PLGA sponge templates showed the highest promotive effect.

Preparation of composite scaffolds composed of gelatin and Au nanostar-deposited black phosphorus nanosheets for the photothermal ablation of cancer cells and adipogenic differentiation of stem cells.

Photothermal nanoparticles are important in photothermal therapy. Combining different nanoparticles can achieve a high photothermal capacity. In this study, composite nanoparticles composed of black phosphorus nanosheets (BPNSs) and gold nanostars (BP-AuNSs) were synthesized by using BPNSs as the reductant. AuNSs were deposited on the BPNSs. The BP-AuNSs were further hybridized with porous gelatin scaffolds to prepare gelatin-BP-AuNS composite scaffolds. The gelatin-BP-AuNS composite scaffolds promoted cell migration and distribution. The synergistic effects of the BPNSs and AuNSs endowed the gelatin-BP-AuNS composite scaffolds with excellent photothermal properties. The gelatin-BP-AuNS composite scaffolds eliminated cancer cells after near infrared laser exposure and supported the adipogenic differentiation of human mesenchymal stem cells. Thus, this gelatin-BP-AuNS composite scaffold holds promise for breast cancer therapy.

PLGA-collagen-BPNS Bifunctional composite mesh for photothermal therapy of melanoma and skin tissue engineering.

The treatment of melanoma requires not only the elimination of skin cancer cells but also skin regeneration to heal defects. To achieve this goal, a bifunctional composite scaffold of poly(DL-lactic-co-glycolic acid) (PLGA), collagen and black phosphorus nanosheets (BPNSs) was prepared by hybridizing a BPNS-embedded collagen sponge with a PLGA knitted mesh. The composite mesh increased the temperature under near-infrared laser irradiation. The incorporation of BPNSs provided the PLGA-collagen-BPNS composite mesh with excellent photothermal properties for the photothermal ablation of melanoma cells both in vitro and in vivo. The PLGA-collagen-BPNS composite mesh had high mechanical strength for easy handling. The PLGA-collagen-BPNS composite mesh facilitated the proliferation of fibroblasts, promoted the expression of angiogenesis-related genes and the genes of components of the extracellular matrix for skin tissue regeneration. The high mechanical strength, photothermal ablation capability and skin tissue regeneration effects demonstrate that the bifunctional PLGA-collagen-BPNS composite mesh is a versatile and effective platform for the treatment of melanoma and the regeneration of skin defects.

Composite scaffolds of black phosphorus nanosheets and gelatin with controlled pore structures for photothermal cancer therapy and adipose tissue engineering.

Breast cancer treatment needs to eradicate cancer cells and restore breast defects after surgical intervention. Herein, bifunctional composite scaffolds of black phosphorus nanosheets (BPNSs) and gelatin were designed to kill breast cancer cells and induce adipose tissue reconstruction. The composite scaffolds were prepared by hybridizing photothermal BPNSs with porous gelatin matrices by adding pre-prepared ice particles to precisely adjust their pore structures. The composite scaffolds had large, well-interconnected spherical pores, which allowed cell migration and infiltration. Hybridization with BPNSs increased the compression strength of the scaffolds. The composite scaffolds possessed a high photothermal conversion capacity that was dependent on the amount of BPNSs. The composite scaffold with a high amount of BPNSs could completely kill breast cancer cells in vitro and in vivo under laser irradiation. Moreover, cell culture and animal experiment results showed that the composite scaffolds promoted lipid oil droplet formation and upregulated the expression of adipogenesis-related genes when hMSCs were cultured in the scaffolds. The composite scaffolds could offer a facile platform to exert anticancer effects against breast cancer cells and promote the reconstruction of adipose tissue.

Implantable multifunctional black phosphorus nanoformulation-deposited biodegradable scaffold for combinational photothermal/ chemotherapy and wound healing.

Surgery is the mainstream treatment for melanoma, but its clinical implementation suffers from some major drawbacks including residual infiltrating melanoma cells at resection margins and severe tissue injury. In this study, a nanocomposite scaffold is developed for in-situ therapy after melanoma surgery as well as wound healing, which is fabricated by embedding photothermal-capable black phosphorus nanosheets (BPNSs) into bioresorbable Gelatin-PCL (GP) nanofibrous scaffold. GP scaffold is a clinically-tested biomaterial with temperature sensitivity and tissue-healing effect, while the BPNSs are loaded with the anticancer antibiotic of doxorubicin (DOX) and conjugated with NH2-PEG-FA for tumor-targeted delivery. The GP scaffold could undergo a sol-gel transition upon NIR irritation and release the BPNSs in situ. During this process, most of the BP-based nanoformulations were selectively internalized by the melanoma cells for the cooperative photothermal therapy and heat-triggerable DOX therapy, while some of the loaded DOX was released into the wound tissue to create a tumor-suppressive microenvironment. Moreover, BPNSs could be gradually degraded to phosphates/phosphonates and thus enhance tissue repair by activating the ERK1/2 and PI3K/Akt pathway. Meanwhile, the detached DOX molecules would also enter the wound tissues for continuous melanoma inhibition. Considering the anti-melanoma and wound healing effect of this composite scaffold, it may offer a facile strategy for the wound treatment after melanoma surgery.

Progress of Iron-Based Nanozymes for Antitumor Therapy.

Artificial nanoscale enzyme-mimics (nanozymes) are promising functional alternatives to natural enzymes and have aroused great interest due to their inherent in vivo stability, affordability, and high catalytic ability. Iron-based nanozymes are one of the most investigated synthetic nanomaterials with versatile enzyme-like catalytic properties and have demonstrated remarkable relevance to a variety of biomedical applications, especially biocatalytic therapy against tumor indications. Nevertheless, despite the recent advances in biology and nanotechnology, the therapeutic performance of iron-based nanozymes in vivo is still limited by technical issues such as low catalytic efficiency and lack of tumor specificity. In this mini review, we briefly summarized the representative studies of iron-based nanozymes, while special emphasis was placed on the current challenges and future direction regarding the therapeutic implementation of iron-based nanozymes for the development of advanced tumor therapies with improved availability and biosafety.

Folic Acid-Functionalized Composite Scaffolds of Gelatin and Gold Nanoparticles for Photothermal Ablation of Breast Cancer Cells.

Photothermal therapy (PTT) has been developed as a useful therapeutic method for cancer treatment. Localization of PTT agents in cancer sites and targeting capacity are required to further increase therapeutic efficacy. In this study, gold nanoparticles (AuNPs) and gelatin were functionalized with folic acid (FA) and hybridized to prepare FA-functionalized gelatin-AuNPs composite scaffolds. AuNPs with rod and star shapes of three sizes (40, 70, and 110 nm) were used for the hybridization to investigate the influence of AuNPs shape and size. The composite scaffolds showed porous structures with good interconnectivity. Modification with FA increased capture capacity of the composite scaffolds. Hybridization with AuNPs rendered the composite scaffold a good photothermal conversion property under near-infrared (NIR) laser irradiation. Temperature change during laser irradiation increased with the laser power intensity and irradiation time. The shape and size of AuNPs also affected their photothermal conversion property. The composite scaffold of gold nanorods 70 (FA-G/R70) had the highest photothermal conversion capacity. Breast cancer cells cultured in the FA-G/R70 composite scaffold were killed under NIR laser irradiation. Mouse subcutaneous implantation further demonstrated the excellent photothermal ablation capability of FA-G/R70 composite scaffold to breast cancer cells. The FA-functionalized composite scaffolds were demonstrated a high potential for local PPT of breast cancer.

A redox-activatable biopolymer-based micelle for sequentially enhanced mitochondria-targeted photodynamic therapy and hypoxia-dependent chemotherapy.

A tumor redox-activatable micellar nanoplatform based on the naturally occurring biomacromolecule hyaluronic acid (HA) was developed for complementary photodynamic/chemotherapy against CD44-positive tumors. Here HA was first conjugated with l-carnitine (Lc)-modified zinc phthalocyanine (ZnPc) via disulfide linkage and then co-assembled with tirapazamine (TPZ) to afford the physiologically stable micellar nanostructure. The mitochondria-targeted photodynamic activity of ZnPc-Lc could efficiently activate the mitochondrial apoptosis cascade and deplete the oxygen in the tumor intracellular environment to amplify the hypoxia-dependent cytotoxic effect of TPZ.

Fabrication of magnesium/zinc-metal organic framework on titanium implants to inhibit bacterial infection and promote bone regeneration.

The residual bacteria in the second revision surgery caused by infection would further lead to the failure of the implantation. Pathogenic bacteria adhesion to an implant surface not only interfere the functions of bone-formation related cells, but also activate the host immune system, thus resulting in inflammation and osteogenesis inhibition. Thus, to fabricate multifunctional (antibacterial, anti-inflammation and pro-osteogenesis) titanium implants is essential to address this issue. In this work, hybrid magnesium/zinc-metal organic framework (Mg/Zn-MOF74) coating was constructed on alkali-heat treated titanium (AT) surface. The hybrid Mg/Zn-MOF74 coating displayed good stability and its stability was related to the content of Zn2+. The MOF74-modified samples were sensitive to bacterial acid microenvironment and displayed strong antibacterial ability against both Escherichia coli and Staphylococcus aureus due to the degradation of MOF74 coating, leading to alkaline microenvironment (about pH 8.0) and degradation products (2,5-dihydroxyterephthalic acid and Zn2+). The coating also showed good early anti-inflammatory property to native Ti substrates. In vivo results further verified that AT-Mg/Zn3 implants had high antibacterial and anti-inflammatory properties at early stage of implantation, and greatly improved new bone formation around implants both at non-infected and infected femur sites.

Fabrication of hyaluronidase-responsive biocompatible multilayers on BMP2 loaded titanium nanotube for the bacterial infection prevention.

Infection associated with orthopedic implants is the chief cause of implant failure. An important consideration to prevent the infection at implants is to inhibit the biofilm formation for the initial 6 h. Therefore, we fabricated hyaluronidase-sensitive multilayers of chitosan (Chi)/sodium hyaluronate-lauric acid (SL) onto the surface of bone morphogenetic protein 2 (BMP2) loaded titanium nanotube (TNT) via spin-assisted layer-by-layer technique. The results of both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (1H NMR) confirmed the successful synthesis of SL. The multilayer structure on BMP2 loaded TNT was characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and water contact angle, respectively. The release profiles confirmed that hyaluronidase could trigger the release of lauric acid (LA) from the SL multilayer and accelerate the release of BMP2 in the system. The hyaluronidase-sensitive-multilayer-coated BMP2-loaded TNT (TNT/BMP2/(Chi/SL/Chi/Gel)4) not only demonstrated good antibacterial capability, but also showed good biocompatibility in in vitro usage, which was supported by the efficient growth inhibition of both Staphylococcus aureus and Escherichia coli, as well as higher cell viability, alkaline phosphatase activity, mineralization capability, and higher gene expression of osteoblasts on TNT/BMP2/(Chi/SL/Chi/Gel)4. This study developed an alternative approach to fabricate effective antibacterial implants for orthopedic implantation.

Engineering of a Nanosized Biocatalyst for Combined Tumor Starvation and Low-Temperature Photothermal Therapy.

Tumor hypoxia is one of the major challenges for the treatment of tumors, as it may negatively affect the efficacy of various anticancer modalities. In this study, a tumor-targeted redox-responsive composite biocatalyst is designed and fabricated, which may combine tumor starvation therapy and low-temperature photothermal therapy for the treatment of oxygen-deprived tumors. The nanosystem was prepared by loading porous hollow Prussian Blue nanoparticles (PHPBNs) with glucose oxidase (GOx) and then coating their surface with hyaluronic acid (HA) via redox-cleavable linkage, therefore allowing the nanocarrier to bind specifically with CD44-overexpressing tumor cells while also exerting control over the cargo release profile. The nanocarriers are designed to enhance the efficacy of the hypoxia-suppressed GOx-mediated starvation therapy by catalyzing the decomposition of intratumoral hydroperoxide into oxygen with PHPBNs, and the enhanced glucose depletion by the two complementary biocatalysts may consequently suppress the expression of heat shock proteins (HSPs) after photothermal treatment to reduce their resistance to the PHPBN-mediated low-temperature photothermal therapies.

Construction of three-dimensional net-like polyelectrolyte multilayered nanostructures onto titanium substrates for combined antibacterial and antioxidant applications.

Bacterial biofilm formation and oxidative stress induced by the production of reactive oxygen species (ROS) are major causes of implant failure. An emerging approach to overcome these issues is to combine chitosan-polycaprolactone (PCL) nanofibers and polyelectrolyte multilayers composed of tannic acid (TA) and gentamicin sulfate (GS) for the localized co-delivery of antioxidants and antibiotics from the titanium surface. The integration of nanofibers (NFs) and layer-by-layer (LBL) technology could provide a larger surface area and thus increase the number of cationic sites of Ti substrates. The coating of NF substrates with TA/GS resulted in higher (p < 0.05 or p < 0.01) cellular activities than those of Ti substrates, including enhanced proliferation and gene expression. Furthermore, in vitro investigation demonstrated that TA/GS-incorporated Ti-polydopamine (PDA)/NF implants exhibited excellent stability, and antibacterial and antioxidant properties. The results showed that Ti-PDA/NF/LBL substrates have a biodegradable character in vivo. All the results indicated that the combination of NFs and the bacteria-triggered antibiotic-releasing coating could be used for the tailored co-delivery of antibacterial and antioxidant agents from various metallic implantable devices to effectively improve early bone healing even under ROS stress and decrease the risk of biofilm-associated infections in patients.

eIF2 alpha phosphorylation alleviates UVA-induced HO-1 expression in mouse epidermal cells.

Ultraviolet A (UVA) irradiation is a potential environmental stressor, which contributes to inflammation, photoaging, and carcinogenesis. UVA causes endoplasmic reticulum stress, hence phosphorylates the α subunit of eIF2. Meanwhile, UVA also induces expression of haem oxygenase-1 (HO-1) and nuclear factor erythroid-derived two related factor 2 (Nrf2) in human skin cells. In mouse JB6 cell, we found high dose UVA could change cell morphology, cause cell viability loss. UVA irradiation activated phosphorylation of eIF2α and Nrf2-HO-1 pathway in a dose-dependent manner. Besides, modulation of eIF2α phosphorylation status could alter expression pattern of Nrf2-HO-1 signalling. Salubrinal, a selective inhibitor of eIF2α dephosphorylation, increased the S phase in cell cycle of JB6 cells after UVA irradiation, suggesting phosphorylation status of eIF2α may affect cellular homeostasis under UVA irradiation. The study directed to further acknowledge about the relationship of UVA-induced eIF2α phosphorylation and Nrf2-HO-1 pathway, which may play a role in phototherapy and photo protection.