It is the challenging goal in cancer biomedicine to search novel cancer-therapeutic modality with concurrent high therapeutic efficiency on combating cancer and low side effects to normal ...cells/tissues. The recently developed nanocatalytic cancer therapy based on catalytic Fenton reaction represents one of the promising paradigms for potential clinical translation, which has got fast progress very recently. This progress report discusses the rational design and fabrication of Fenton reaction-based nanocatalysts for triggering the in-situ Fenton chemical reaction within tumor microenvironment to generate highly toxic hydroxyl radicals (•OH), which is highly efficient for killing the cancer cells and suppressing the tumor growth. Several strategies for optimizing the nanocatalytic cancer-therapeutic efficiency of Fenton reaction have been highlighted, including screening high-performance Fenton nanocatalysts, increasing peroxide-hydrogen amounts as the reactants, changing the Fenton-reaction conditions (e.g., temperature, acidity and photo-triggering), and Fenton reaction-based synergistic cancer therapy such as some sequential nanocatalytic reactions with improved therapeutic outcome. The facing challenges and future developments of Fenton reaction-based nanocatalytic cancer therapy are also discussed for further promoting the clinical translation of this emerging cancer-therapeutic modality to benefit the cancer patients.
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Layered double hydroxide (LDH)-based nanocomposites, constructed by interacting LDH nanoparticles with other nanomaterials (e.g. silica nanoparticles and magnetic nanoparticles) or polymeric ...molecules (e.g. proteins), are an emerging yet active area in healthcare, environmental remediation, energy conversion and storage. Combining advantages of each component in the structure and functions, hierarchical LDH-based nanocomposites have shown great potential in biomedicine, water purification, and energy storage and conversion. This feature article summarises the recent advances in LDH-based nanocomposites, focusing on their synthesis, structure, and application in drug delivery, bio-imaging, water purification, supercapacitors, and catalysis.
Recently, more and more multi/many-objective algorithms have been proposed. However, most evolutionary algorithms only focus on solving small-scale multi/many-objective optimization problems, and few ...researchers pay attention to solving large-scale optimization problems. Like NSGA-III, although it performs well in solving many-objective optimization problems, it does not perform well in large-scale optimization problems. To solve this problem, in this paper, we introduce the information feedback models to improve the ability of NSGA-III to solve large-scale optimization problems. In the feedback models, the historical information of individuals in the previous generations is used in the update process of the current generation. According to the different ways of selecting individual, information feedback models are divided into two categories: one is to select individuals in a fixed way (called M-F) and the other is to select individuals randomly (called M-R). For each type of model, if the number of individuals selected is different, the information feedback models also have some difference. According to the number and mode of individual selection, there are six models in this paper. These six models are respectively embedded into NSGA-III to generate six improving NSGA-III algorithms (these six algorithms are collectively referred to as IFM-NSGAIII). These six algorithms are compared with the original NSGA-III on 9 benchmark problems to search the best information feedback model and the best IFM-NSGAIII algorithm. Then the two best IFM-NSGAIII algorithms are compared with four state-of-the-art algorithms on 9 test functions. Experiments show that the proposed algorithms are highly competitive on test problems.
•Information feedback models are to improve NSGA-III to solve large-scale problems.•Individuals’ historical information was reused via the information feedback model.•Individuals’ historical information is selected with a fixed way or randomly.
Developing nanocarrier systems with sufficient drug loading ability and efficient drug release behavior in cells is a powerful strategy to maximize therapeutic efficacies and minimize side effects of ...administered drugs. However, the two aspects are usually contradictory in a single nanocarrier. Herein, polyphenol-DNA nanocomplex with controllable assembly/disassembly behaviors is developed for responsive and sequential drug release in cancer cells. Programmable assembly of branched-DNA achieves multiple-gene loading, afterwards tannic acid (TA), plant-derived polyphenols as drugs mediate assembly of branched-DNA to form nanocomplex. Intracellularly, two-step disassembly process of nanocomplex enables efficient gene/drug release. Lysosomal acidic microenvironment induces the disassembly of nanocomplex to release TA and branched-DNA. Glutathione and DNase I in cytoplasm trigger the precise release of genes from branched-DNA. The efficacy of multiple-gene/chemo-therapy is demonstrated using in vitro and in vivo models. This work provides a controllable assembly/disassembly route to resolve the conflict between sufficient drug loading and efficient drug release in cells for therapeutics.
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DNA nanostructures have been demonstrated as promising carriers for gene delivery. In the carrier design, spatiotemporally programmable assembly of DNA under nanoconfinement is important but has ...proven highly challenging due to the complexity-scalability-error of DNA. Herein, a DNA nanotechnology-based strategy via the cascade hybridization chain reaction (HCR) of DNA hairpins in polymeric nanoframework has been developed to achieve spatiotemporally programmable assembly of DNA under nanoconfinement for precise siRNA delivery. The nanoframework is prepared via precipitation polymerization with Acrydite-DNA as cross-linker. The potential energy stored in the loops of DNA hairpins can overcome the steric effect in the nanoframework, which can help initiate cascade HCR of DNA hairpins and achieve efficient siRNA loading. The designer tethering sequence between DNA and RNA guarantees a triphosadenine triggered siRNA release specifically in cellular cytoplasm. Nanoframework provides stability and ease of functionalization, which helps address the complexity-scalability-error of DNA. It is exemplified that the phenylboronate installation on nanoframework enhanced cellular uptake and smoothed the lysosomal escape. Cellular results show that the siRNA loaded nanoframework down-regulated the levels of relevant mRNA and protein. In vivo experiments show significant therapeutic efficacy of using siPLK1 loaded nanoframework to suppress tumor growth.
DNA nanostructures have shown excellent prospects in biomedical applications owing to their unique sequence programmability, function designability, and biocompatibility. As a type of unique ...DNA–inorganic hybrid nanostructures, DNA nanoflowers (DNFs) have attracted considerable attention in the past few years. Precise design of the DNA sequence enables the functions of DNFs to be customized. Specifically, DNFs exhibit high physiological stability and more diverse properties by virtue of the incorporation of inorganic materials, which in turn have been applied in an assortment of biomedical fields. In this review, the design, synthesis, and biomedical applications of programmable DNFs are discussed. First, the background of DNA‐based materials and the fundamentals of DNFs are briefly introduced. In the second part, two synthetic methods of DNFs are categorized as the rolling circle amplification and salt aging method, focusing on the formation mechanism of DNFs and differences between the synthetic methods. In the third part, the biomedical applications of DNFs functional materials are summarized, including biosensing, bioimaging, and therapeutics. Finally, the challenges and future opportunities of DNFs are discussed toward more widespread applications.
Flower of the flock: DNA nanoflowers consisting of DNA molecules and inorganic skeletons show flower‐like morphology and porous structure. The DNA sequences and inorganic components can be designed in a predefined and programmable fashion, and eventually generate DNA nanoflowers with precise structures and synergistic functions, which can be widely applied in biomedical and related fields.
Metastasis is the primary cause of cancer morbidity and mortality. To obtain an effective diagnosis and treatment, precise imaging of tumor metastasis is required. Here we prepared persistent ...luminescent nanoparticles (PLNPs) containing a hydrogel (PL-gel) for targeted, sustained, and autofluorescence-free tumor metastasis imaging. PLNPs offered renewable long-lasting near-infrared (NIR) emitting without in situ radiation, favoring deep tissue penetration imaging without background interference. PLNPs were conjugated with 4-carboxyphenyl boronic acid (CPBA) to yield PLNPs-CPBA, which specifically recognized metastatic breast cancer cells (MBA-MD-231 cells) and enabled receptor-mediated endocytosis for specific cancer cell labeling. The PLNPs-CPBA-labeled cancer cells enabled sensitive imaging performance and high viability without influencing the migration and invasiveness of cancer cells for long-term tracking. PLNPs-CPBA were further encapsulated inside alginate to generate PL-gel for sustained PLNPs-CPBA release and tumor cell labeling, and the PL-gel showed enhanced renewable persistent luminescence compared to the PLNPs-CPBA suspension. The metastasis in the mouse breast cancer model was continuously tracked by persistent luminescence imaging, showing that PL-gel achieved noninvasive and highly selective imaging of tumor metastasis without background interference. Our PL-gel could be rationally designed to specifically target other types of cancer cells and thus provide a powerful and generic platform for the study of tumor metastasis.
Proteasome is a large proteolytic complex that consists of a 20S core particle (20SP) and 19S regulatory particle (19SP) in eukaryotes. The proteasome degrades most cellular proteins, thereby ...controlling many key processes, including gene expression and protein quality control. Proteasome dysfunction in plants leads to abnormal development and reduced adaptability to environmental stresses. Previous studies have shown that proteasome dysfunction upregulates the gene expression of proteasome subunits, which is known as the proteasome bounce-back response. However, the proteasome bounce-back response cannot explain the damaging effect of proteasome dysfunction on plant growth and stress adaptation. To address this question, we focused on downregulated genes caused by proteasome dysfunction. We first confirmed that the 20SP subunit PBE is an essential proteasome subunit in Arabidopsis and that PBE1 mutation impaired the function of the proteasome. Transcriptome analyses showed that hypoxia-responsive genes were greatly enriched in the downregulated genes in pbe1 mutants. Furthermore, we found that the pbe1 mutant is hypersensitive to waterlogging stress, a typical hypoxic condition, and hypoxia-related developments are impaired in the pbe1 mutant. Meanwhile, the 19SP subunit rpn1a mutant seedlings are also hypersensitive to waterlogging stress. In summary, our results suggested that proteasome dysfunction downregulated the hypoxia-responsive pathway and impaired plant growth and adaptability to hypoxia stress.
Objectives
The fibroblast growth factor receptor (FGFR) members including FGFR1–4 have been identified as promising novel therapeutic targets and prognostic markers in multiple solid tumors. However, ...the predictive role of the expression of FGFR proteins in oral squamous cell carcinoma (OSCC) requires further exploration.
Materials and Methods
Immunohistochemical evaluation of FGFR1–4 was performed on 161 paired OSCC samples. The associations of FGFRs with clinicopathologic and prognostic parameters were analyzed. To further assess the contribution of FGFRs to OSCC proliferation, cell lines, and one PDX model was utilized to examine the anti‐tumor effect of the pan‐FGFR inhibitor AZD4547.
Results
All FGFR members were found to be overexpressed in OSCC tumors when compared to normal tissues, and their expression was significantly associated with poor overall survival and disease‐free survival. Multivariate Cox regression analysis revealed high expression of FGFR1 (p = 0.014) and FGFR4 (p = 0.009) were independent prognostic factors and co‐overexpression of FGFR1 and FGFR4 with lymph node metastasis increased HR for death (p = 0.02). The pan‐FGFR inhibitor AZD4547 showed anti‐tumor activity in cell lines and in a patient‐derived xenograft of OSCC.
Conclusions
This study highlights the co‐overexpression of FGFR1 and FGFR4 as a significantly poor prognosis indicator in OSCC when combined with lymph node metastasis.
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