Cationic Polythiophene as Gene Carrier and Sonosensitizer for Sonodynamic Synergic Gene Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal and highly malignant tumors. Sonodynamic therapy (SDT) is a new cancer treatment method. One of its unique advantages lies in the treatment of deep tumors due to its excellent tissue penetration ability caused by ultrasound (US). However, most sonosensitizers suffer from weak sonodynamic activity and poor tumor-targeting ability. In addition, small interfering RNA (siRNA) is a promising anticancer drug, and the efficacy of siRNA-based gene therapy largely depends on the cell impermeability of the gene carrier. Here, we designed and synthesized a cationic polythiophene derivative (PT2) that can be used as a siRNA carrier for gene therapy. Moreover, PT2 could generate singlet oxygen (1O2) and hydroxyl radicals (O2•-) under US irradiation, which suggests that PT2 could be used for SDT. Our study discovered that NUDT1 promoted HCC proliferation and inhibited intracellular ROS production. Therefore, si-NUDT1 was designed and synthesized. NUDT1 silencing can inhibit the proliferation of tumor cells and increase the production of intracellular ROS to further improve the efficacy of SDT. Then, si-NUDT1 assembled with PT2 and DSPE-PEG-FA to prepare a novel tumor-targeting nanodrug (PT2-siRNA@PEG-FA) for synergic SDT and gene therapy of HCC.

Sorafenib and tetrakis (4-carboxyphenyl) porphyrin assembled nanoparticles for synergistic targeted chemotherapy and sonodynamic therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is characterized by a high degree of malignancy and mortality. Sorafenib (SOR), a multi-kinase inhibitor, is clinically used in the treatment of HCC. However, SOR suffers from serious side effects and drug resistance. The development of novel therapeutic strategies for HCC therapy is urgently needed. Sonodynamic therapy (SDT) has unique advantages in treating deep tumors due to the merits of deep tissue penetration, low side effects, and the absence of drug resistance. Here, we developed multifunctional nanoparticles (NPs) termed SOR-TCPP@PEG-FA by assembling SOR, tetrakis (4-carboxyphenyl) porphyrin (TCPP), and folic acid (FA)-modified DSPE-PEG. The FA group enhances the tumor targeting capability of these NPs, while TCPP generates ROS under ultrasound (US) irradiation, which are toxic to tumor cells, and SOR with chemotherapeutic effects is released, thus realizing the synergistic SDT and chemotherapy of tumors.

Regulating photochemical properties of carbon dots for theranostic applications.

As a new zero-dimensional carbon-based material, carbon dots (CDs) have attracted extensive attention owing to their advantages such as easy preparation and surface modification, good biocompatibility and water solubility, and tunable photochemical properties. CDs have become one of the most promising nanomaterials in the field of fluorescent sensing, bioimaging, and cancer therapy. How to precisely regulate the photochemical properties, especially the absorption, fluorescence, phosphorescence, reactive oxygen species generation, and photothermal conversion of the CDs, is the key to developing highly efficient phototheranostics for cancer treatment. Although many studies on cancer therapy using CDs have been published, no review has focused on the regulation of photochemical properties of CDs for phototheranostic applications. In this review, we summarized the strategies such as the selection of suitable carbon source, heteroatomic doping, optimum reaction conditions, surface modification, and assembly strategy to efficiently regulate the photochemical properties of the CDs to meet the requirements of different practical applications. This review might provide some valuable insight and new ideas for the development of CDs with excellent phototheranostic performance. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Lysosome- and plasma membrane-accumulative and tumor-targetable polythiophene nanoparticles for enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) has emerged as a promising treatment approach of solid tumors given its deep tissue penetration, non-invasiveness, few side effects, and negligible drug resistance. Herein, we report the first polythiophene derivative-based sonosensitizer (PT2) containing a quaternary ammonium salt and dodecyl chains with better ultrasound stability than that of traditional sonosensitizers, such as Rose Bengal and chlorin e6. PT2 was encapsulated by folic acid-containing polyethylene glycol. The obtained nanoparticles (PDPF NPs) exhibited excellent biocompatibility, cancer cell-targeting capacity, and accumulated mainly in the lysosomes and plasma membranes of cells. These NPs could generate singlet oxygen and superoxide anions simultaneously under ultrasound irradiation. In vitro and in vivo experimental results demonstrated that PDPF NPs could induce cancer-cell death through apoptosis and necrosis, inhibit DNA replication, and ultimately achieve tumor depletion upon US irradiation. These findings revealed that polythiophene could serve as an efficacious sonosensitizer for enhanced US treatment of deep-seated tumors.

Catalase-like pleated niobium carbide MXene loaded with polythiophene for oxygenated sonodynamic therapy in solid tumor.

Sonodynamic therapy (SDT), an emerging treatment for solid tumors, has the advantages of deep tissue penetration, non-invasiveness, low side effects, and negligible drug resistance. However, the hypoxic environment of deep solid tumors can discount the efficacy of oxygenated dependent SDT. Here, we synthesized a polythiophene-based sonosensitizer (PT2) and a two-dimensional pleated niobium carbide (Nb2C) Mxene. PT2 was loaded onto the surface of poly(vinylpyrrolidone) (PVP)-coated Nb2C MXene through electrostatic interaction to obtain Nb2C-PVP-PT2 nanosheets (NSs) with a high loading efficiency of 153.7%. Nb2C MXene exhibited catalase-like activity, which could catalyze hydrogen peroxide (H2O2) to produce O2, in turn alleviating tumor hypoxia and enhancing the efficacy of SDT. The depletion of H2O2 further results in abnormal cellular H2O2 levels and reduced tumor cell activity. Moreover, the decomposed NSs led to the release of the sonosensitizer PT2 that can efficiently generate both singlet oxygen and superoxide anions under ultrasound irradiation. These events led to the inhibition of DNA replication of tumor cells, causing tumor cell death, allowing for enhanced SDT efficacy.

Getting drugs to the brain: advances and prospects of organic nanoparticle delivery systems for assisting drugs to cross the blood-brain barrier.

The blood-brain barrier (BBB) plays an irreplaceable role in protecting the central nervous system (CNS) from bloodborne pathogens. However, the BBB complicates the treatment of CNS diseases because it prevents almost all therapeutic drugs from getting into the CNS. With the growing understanding of the physiological characteristics of the BBB and the development of nanotechnology, nanomaterial-based drug delivery systems have become promising tools for delivering drugs across the BBB to the CNS. Herein, we systematically summarize the recent progress in organic-nanoparticle delivery systems for treating CNS diseases and evaluate their mechanisms in overcoming the BBB with the aim to provide a comprehensive understanding of the advantages, disadvantages, and challenges of organic nanoparticles in delivering drugs across the BBB. This review may inspire new research ideas and directions for applying nanotechnology to treat CNS diseases.

Photovoltaic molecules with ultra-high light energy utilization for near-infrared laser triggered synergetic photodynamic and photothermal therapy.

Photovoltaic molecules possess strong absorption in the near-infrared (NIR) region and are suitable for NIR laser-triggered phototherapy. Herein, the star molecule IEICO of organic photovoltaic materials, which has a narrow bandgap and large A-D-A conjugated structure, was prepared into water dispersive nanoparticles (NPs) through a simple self-assembly method. The obtained IEICO NPs showed a strong NIR absorption peak at 800 nm and a high 1O2 quantum yield of 11% and photothermal conversion efficiency of 85.4% under 808 nm laser irradiation. The ultra-high light energy utilization efficacy (∼96.4%) of the IEICO NPs enables their excellent phototherapeutic effect on tumors. The present work suggested the huge application potential of organic photovoltaic materials in the biomedical field.

A water-soluble thiophene-croconaine dye with a high molar extinction coefficient for NIR fluorescence imaging-guided synergistic photothermal/photodynamic therapy of cancer.

Phototherapeutic agents with near-infrared (NIR) fluorescence, strong reactive oxygen species generation and photothermal conversion capabilities are highly desirable for use in cancer therapy. Herein, a water-soluble NIR croconaine dye (TCR) with a thiophene-croconaine rigid core and two symmetric alkyl chains was designed and synthesized. TCR exhibits intense NIR absorption and fluorescence that peaked at 780 and 815 nm, respectively, with a high molar extinction coefficient of 1.19 × 105 M-1 cm-1. Moreover, TCR has a high photothermal conversion efficiency of 77% and is capable of generating hydroxyl radicals (OH˙) under 735 nm laser irradiation. Based on these outstanding properties, TCR has proven its application in NIR fluorescence imaging-guided synergistic photothermal/photodynamic therapy of cancer.

Sol-gel hydrothermal synthesis of nano crystalline silicotitanate and its strontium and cesium adsorption.

Crystalline silicotitanate (CST) was synthesized via a sol-gel hydrothermal method using Na2Si2O3·9H2O and TiCl4 as silicon and titanium sources. The effects of pH, silicon concentration, hydrothermal temperature, and time on the CST synthesis were studied at a fixed molar ratio of silicon:titanium (0.98:1). Pure nano-CST crystals were synthesized at pH = 12.5, silicon concentration of 5 g L-1, 170 °C for 7 days. The average CST particle size was < 100 nm, with a Sr2+/Cs+ distribution coefficient up to 1.9 × 106 mL g-1/9.4 × 103 mL g-1 under the optimum conditions. In addition, nano-CST absorbed Sr2+/Cs+ over a wide pH range. The nano-CST also displayed a much faster equilibrium time, 4 h, as compared with previous studies. Furthermore, nano-CST adsorption of Sr2+/Cs+ followed a Langmuir adsorption model and was consistent with pseudo-second-order kinetics.

[Characteristics of dissolved organic carbon release under inundation from typical grass plants in the water-level fluctuation zone of the Three Gorges Reservoir area].

The water-level fluctuation zone of the Three Gorges Reservoir (TGR) exposes in spring and summer, then, green plants especially herbaceous plants grow vigorously. In the late of September, water-level fluctuation zone of TGR goes to inundation. Meanwhile, annually accumulated biomass of plant will be submerged for decaying, resulting in organism decomposition and release a large amount of dissolved organic carbon (DOC). This may lead to negative impacts on water environment of TGR. The typical herbaceous plants from water-level fluctuation zone were collected and inundated in the laboratory for dynamic measurements of DOC concentration of overlying water. According to the determination, the DOC release rates and fluxes have been calculated. Results showed that the release process of DOC variation fitted in a parabolic curve. The peak DOC concentrations emerge averagely in the 15th day of inundation, indicating that DOC released quickly with organism decay of herbaceous plant. The release process of DOC could be described by the logarithm equation. There are significant differences between the concentration of DOC (the maximum DOC concentration is 486.88 mg x L(-1) +/- 35.97 mg x L(-1) for Centaurea picris, the minimum is 4.18 mg x L(-1) +/- 1.07 mg x L(-1) for Echinochloacrus galli) and the release amount of DOC (the maximum is 50.54 mg x g(-1) for Centaurea picris, the minimum is 6.51 mg x g(-1) for Polygonum hydropiper) due to different characteristics of plants, especially, the values of C/N of herbaceous plants. The cumulative DOC release quantities during the whole inundation period were significantly correlated with plants' C/N values in linear equations.