Huiyu Liu

Two-Dimensional Nanomaterials for Cancer Nanotheranostics.

Emerging nanotechnologies show unprecedented advantages in accelerating cancer theranostics. Among them, two-dimensional nanomaterials (2DNMs) represent a novel type of material with versatile physicochemical properties that have enabled a new horizon for applications in both cancer diagnosis and therapy. Studies have demonstrated that 2DNMs may be used in diverse aspects, including i) cancer detection due to their high propensity towards tumor markers; ii) molecular imaging for guided tumor therapies, and iii) drug and gene loading, photothermal and photodynamic cancer therapies. However, their biomedical applications raise concerns due to the limited understanding of their in vivo metabolism, transformation and possible toxicities. In this comprehensive review, the state-of-the-art development of 2DNMs and their implications for cancer nanotheranostics are presented. The modification strategies to enhance the biocompatibility of 2DNMs are also reviewed.

Advances in biodegradable nanomaterials for photothermal therapy of cancer

Photothermal cancer therapy is an alternative to chemotherapy, radiotherapy, and surgery. With the development of nanophotothermal agents, this therapy holds immense potential in clinical translation. However, the toxicity issues derived from the fact that nanomaterials are trapped and retained in the reticuloendothelial systems limit their biomedical application. Developing biodegradable photothermal agents is the most practical route to address these concerns. In addition to the physicochemical properties of nanomaterials, various internal and external stimuli play key roles on nanomaterials uptake, transport, and clearance. In this review, we summarized novel nanoplatforms for photothermal therapy; these nanoplatforms can elicit stimuli-triggered degradation. We focused on the recent innovative designs endowed with biodegradable photothermal agents under different stimuli, including enzyme, pH, and near-infrared (NIR) laser.

Carbon nanotubes stimulate synovial inflammation by inducing systemic pro-inflammatory cytokines

Carbon nanotubes (CNTs) have promising applications in a wide range of biomedical fields, including imaging, drug/gene delivery and other therapeutics; however, the biosafety concerns of CNTs should be addressed. To date, many reports have documented the toxicological effects on the cells, tissue or organs that are in direct contact with the tubes; however, there is limited evidence to unravel the secondary toxicity upon CNT treatment. Moreover, more effort is needed to gain a definitive understanding of the adverse outcome pathway (AOP) for CNTs, and a pragmatic framework for risk assessment has not been established yet. In the current study, we aimed to decipher the secondary toxicity to joints under CNT exposure. We demonstrated that carboxylated multi-wall CNTs (MWCNTs-COOH) significantly provoked systemic pro-inflammatory responses, leading to synovial inflammation within knee joints, as evidenced by the infiltration of pro-inflammatory cells in the synovium and meniscus. Mechanistic studies showed that MWCNTs-COOH stimulated pro-inflammatory effects by activating macrophages, and the secreted pro-inflammatory cytokines primed the synoviocytes and chondrocytes, resulting in enhanced production of a large array of enzymes involved in articular cartilage degeneration, including matrix metalloproteinase (MMP) members and cyclooxygenase (COX) members, and increased enzymatic activity of MMPs was demonstrated. Blockade of the cytokines by antibodies significantly attenuated the production of these enzymes. Our current study thus suggests that there is a novel secondary toxicity of CNTs, namely a new AOP to understand the indirect effects of carbon nanotubes: synovial inflammation due to the alteration of the priming state of synoviocytes and chondrocytes under CNT-induced systemic inflammatory conditions.

Low-Dose Bisphenol A Exposure: A Seemingly Instigating Carcinogenic Effect on Breast Cancer

Breast cancer is the fifth most common cause of cancer death in the world and the second most common fatal cancer in women. Epidemiological studies and clinical data have indicated that hormones, including estrogen, progesterone, and prolactin, play important roles in the initiation and progression of breast cancer. Bisphenol A (BPA) is one of the most commonly used and thoroughly studied endocrine disruptors. It can be released from consumer products and deposited in the environment, thus creating potential for human exposure through oral, inhaled, and dermal routes. Some recent reviews have summarized the known mechanisms of endocrine disruptions by BPA in human diseases, including obesity, reproductive disorders, and birth defects. However, large knowledge gaps still exist on the roles BPA may play in cancer initiation and development. Evidence from animal and in vitro studies has suggested an association between increased incidence of breast cancer and BPA exposure at doses below the safe reference doses that are the most environmentally relevant. Most current studies have paid little attention to the cancer‐promoting properties of BPA at low doses. In this review, recent findings on the carcinogenic effects of low‐dose BPA on breast cancer and discussed possible biologic mechanisms are summarized.

A Comparative Study of Clinical Intervention and Interventional Photothermal Therapy for Pancreatic Cancer

Although nanoparticle-based photothermal therapy (PTT) has been intensively investigated recently, its comparative efficiency with any clinical cancer treatments has been rarely explored. Herein for the first time we report a systematic comparative study of clinical iodine-125 (125 I) interstitial brachytherapy (IBT-125-I) and interventional PTT (IPTT) in an orthotopic xenograft model of human pancreatic cancer. IPTT, based on the nanoparticles composing of anti-urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) modified gold nanoshells (hereinafter uIGNs), is directly applied to local pancreatic tumor deep in the abdomen. In comparison to IBT-125-I, a 25% higher median survival rate of IPTT with complete ablation by one-time intervention has been achieved. The IPTT could also inhibit pancreatic tumor metastasis which can be harnessed for effective cancer immunotherapy. All results show that this IPTT is a safe and radical treatment for eradicating tumor cells, and may benefit future clinical pancreatic cancer patients.

Hydrophilic Polyelectrolyte Multilayers Improve the ELISA System: Antibody Enrichment and Blocking Free

In this study, polyelectrolyte multilayers were fabricated on a polystyrene (PS) plate using a Layer-by-Layer (LbL) self-assembly technique. The resulting functional platform showed improved performance compared with conventional enzyme-linked immunosorbent assay (ELISA) systems. Poly(diallyldimethylammonium chloride) (PDDA) and poly(acrylic acid) (PAA) were used as cationic and anionic polyelectrolytes. On the negatively-charged (PDDA/PAA)3 polyelectrolyte multilayers the hydrophilic PAA surface could efficiently decrease the magnitude of the noise signal, by inhibiting nonspecific adsorption even without blocking reagent adsorption. Moreover, the (PDDA/PAA)3 substrate covalently immobilized the primary antibody, greatly increasing the amount of primary antibody adsorption and enhancing the specific detection signal compared with a conventional PS plate. The calibration curve of the (PDDA/PAA)3 substrate showed a wide linear range, for concentrations from 0.033 to 33 nM, a large specific signal change, and a detection limit of 33 pM, even though the conventional blocking reagent adsorption step was omitted. The (PDDA/PAA)3 substrate provided a high-performance ELISA system with a simple fabrication process and high sensitivity; the system presented here shows potential for a variety of immunosensor applications.

Metal-Organic-Framework-Derived Carbon Nanostructure Augmented Sonodynamic Cancer Therapy

Sonodynamic therapy (SDT) can overcome the critical issue of depth-penetration barrier of photo-triggered therapeutic modalities. However, the discovery of sonosensitizers with high sonosensitization efficacy and good stability is still a significant challenge. In this study, the great potential of a metal-organic-framework (MOF)-derived carbon nanostructure that contains porphyrin-like metal centers (PMCS) to act as an excellent sonosensitizer is identified. Excitingly, the superior sonosensitization effect of PMCS is believed to be closely linked to the porphyrin-like macrocycle in MOF-derived nanostructure in comparison to amorphous carbon nanospheres, due to their large highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap for high reactive oxygen species (ROS) production. The nanoparticle-assisted cavitation process, including the visualized formation of the cavitation bubbles and microjets, is also first captured by high-speed camera. High ROS production in PMCS under ultrasound is validated by electron spin resonance and dye measurement, followed by cellular destruction and high tumor inhibition efficiency (85%). This knowledge is important from the perspective of understanding the structure-dependent SDT enhancement of a MOF-derived carbon nanostructure.

In Situ Growth of Pd Nanosheets on g-C3N4 Nanosheets with Well-Contacted Interface and Enhanced Catalytic Performance for 4-Nitrophenol Reduction

Loading novel metal nanosheets onto nanosheet support can improve their catalytic performance, but the morphological incompatibility makes it difficult to construct a well-contacted interface, which is of particular interest in supported catalysts. Herein, Pd nanosheets (Pd NSs) are supported onto graphitic carbon nitride nanosheets (CNNSs) with intimate face-to-face contact through an in situ growth method. This method overcomes the limitations of the morphological incompatibility and ensures the intimate interfacial contact between Pd NSs and CNNSs. The nitrogen-rich nature of CNNSs endows Pd NSs with abundant anchoring sites, which optimizes the electronic structure and improves the chemical and morphological stability of Pd NSs. The supported Pd NSs demonstrate high dispersion and exhibit largely enhanced activity toward the reduction of 4-nitrophenol. The concentration-normalized rate constant is up to 3052 min-1 g-1 L, which is 5.4 times higher than that obtained by unsupported Pd NSs. No obvious deactivation is observed after six runs of the recycling experiments. It is believed that the supported novel metal nanosheets with the intimately contacted interface may show promising applications in catalysis.

Multifunctional Mesoporous/Hollow Silica for Cancer Nanotheranostics

Recently, mesoporous/hollow silica (MHSN) has attracted considerable attention for their biomedical application. With their special structure and properties of high surface, uniformly sized, excellent biocompatibility, easily surface functionalization, ease of large-scale synthesis and low cost, MHSN-based nanoparticles show great advantages in drug delivery and imaging system. In this chapter, we discuss the recent research progress of MHSN-based theranostic applications. Firstly, the development of MHSN-based fluorescent optical imaging and medical imaging is introduced. Then, we overview the building up and application of MHSN-based imaging-guided therapies, as well as the understanding of the functional modalities which may affect the transport, delivery, and release of the MHSN loading cargos. In the end, the potential limitation and challenge related to the successful applications of multifunctional MHSN nanomaterials in clinical are concluded. We anticipate that the MHSN-based nanocomposites will open a new era of inorganic nanomaterials for the effective personalized cancer therapy in clinical in the near future.

Rod-shaped cavitation bubble structure in ultrasonic field

Rod-shaped cavitation bubble structure in thin liquid layers in ultrasonic field is investigated experimentally. It is found that cavitation structure successively experiences several stages with the change of the thickness of the thin liquid layer. Rod-shaped structure is a stable structure of the boundary between the cavitation cloud region and the non-cavitation liquid region, which can be formed in two different ways. Cavitation bubbles in a thin liquid layer have a distribution in the thickness direction. The rod-shaped structures tend to crosslink with each other to form stable Y-branch structures. The angle of the Y-branch structure is Gauss distribution with mathematical expectation μ = 119.93. A special rod-shaped cavitation structure with source is also investigated in detail. Due to the pressure gradient in the normal direction, the primary Bjerknes force causes the bubbles in the rod-shaped structure on both sides to converge to the axis. The secondary Bjerknes forces between the bubbles also make the cluster converge, so the large bubbles which are attached to the radiating surface tend to align themselves along the central line. According to the formula deduced in this paper, the variation of curvature of curved rod-shaped structure is qualitatively analyzed. The Y-branch structure of cavitation cloud and Plateau boundary of soap bubbles are compared.