Polymers with platinum drugs and other macromolecular metal complexes for cancer treatment

Metal-based anticancer drugs, in particular platinum-drugs, have been investigated for the treatment of cancer for the last 40 years. A small set of platinum-based drugs have meanwhile received FDA approval for the treatment of various cancer. Cisplatin and its relatives are currently one of the most widely used anticancer drugs. The use is however associated with significant side effects and rising drug resistance. To combat these problems, drug delivery carriers have been developed to increase the protection of the drug and increase efficacy. Metal-based drugs represent a rather unique drug delivery challenge. Most anticancer drugs are either physically encapsulated into a polymer matrix or they can be conjugated to the polymer via a degradable linker. While both pathways are possible for metal-based drugs, the conjugation to the polymer can be carried via labile or permanent ligands. In addition, the prodrug strategy using the drug in the higher oxidation state is a common approach that has been widely tested for platinum drug. The delivery of platinum drugs is now a mature field and the various conjugation techniques have been combined with a range of drug carriers including dendrimers, micelles and solid polymer nanoparticles. Hybrids of macromolecular metal complexes with inorganic nanoparticles have been tested in recent years to combine the ability to deliver the drug with imaging properties. An emerging trend is the surface decoration of the polymeric nanoparticles with targeting ligands such as folates. The advanced state of this field is evident by the fact that some macromolecular platinum drugs even advanced to the clinic. While the delivery of platinum drugs has been well explored, the delivery of other metal-based drugs based on gold, ruthenium or cobalt is still in their infancy.     

基于核酸适体-纳米金银染放大的玉米赤霉烯酮快速检测方法研究（网络首发、推荐阅读）

玉米赤霉烯酮（Zearalenone,ZEA）具有较强的生殖毒性、致突变和致畸作用。以ZEA适体为识别元件,构建了基于纳米金诱导聚集和银染放大的ZEA适体比色可视化检测方法。结果表明,在优化条件下,ZEA浓度在5~200 ng/mL范围内与体系的吸光度值呈良好的线性关系,其线性回归方程为y= 0.248 6+0.000 461 56x (R2=0.990 2),最低检测限为5 ng/mL,且方法特异性良好。进一步通过银染作用将该方法的灵敏度提高了50倍。经对比,该方法对实际样品的检测结果与酶联免疫法基本一致,为食品中ZEA的快速检测提供了简便有效的新策略。     

Electrochemical glucose biosensing by pyranose oxidase immobilized in gold nanoparticle-polyaniline/AgCl/gelatin nanocomposite matrix

A novel pyranose oxidase (PyOx) biosensor based on gold nanoparticles (AuNPs)–polyaniline(PANI)/AgCl/gelatin nanocomposite has been developed for the glucose detection. PyOx was immobilized on the surface of glassy carbon electrode (GCE) via the nanocomposite matrix. The electrode surface was imaged by scanning electron microscopy (SEM). Amperometric detection of the consumed oxygen during the enzymatic reaction was monitored at −0.7 V. After optimization studies, analytical characterization of the biosensor was carried out. The linear response of the AuNPs–AgCl/PANI/gelatin modified PyOx biosensor is found to be from 0.05 to 0.75 mM glucose with the equation of y = 2.043x + 0.253; R² = 0.993. Finally, proposed biosensor was used to analyze glucose content in real samples. Obtained data from the biosensing system was compared with a commercial enzyme assay kit based on spectrophotometric Trinder reaction as a reference method.     

Prescribing DNA Origami Patterns via Scaffold Decoration

DNA origami has rapidly emerged as a powerful technique to fabricate user‐defined DNA nanostructures. However, the ability to custom‐make patterns on DNA origami template is hampered by the heavy workload and high cost of changing staple DNA (up to several hundred strands per set). Here, a scaffold‐decorated DNA origami method is developed by prescribing the pattern information to the scaffold DNA. For each pixel of an origami, a designed “pixel strand” (P‐strand) is hybridized to the scaffold, strongly preoccupying a specific position and competing with invading staples in a mild origami assembly. To fabricate a new origami pattern, the P‐strand set needs to be replaced with a universal staple set. The yield of thus‐fabricated DNA origami patterns is comparable to a conventional DNA origami with canonical method. One‐pot fabrication of three different nanopatterns in a single test‐tube is further demonstrated. Also, dynamic switch of the pattern is shown. This method provides a generic approach and offers large flexibility for scaling up the nanofabrication with DNA origami by kinetically modulating the reaction pathway of the staples with the scaffold DNA, which represents a novel route in the self‐assembly of complex biomolecular systems.     

Oxidative Damage to Mitochondria Enhanced by Ionising Radiation and Gold Nanoparticles in Cancer Cells

Gold nanoparticles (AuNP) can increase the efficacy of radiation therapy by sensitising tumor cells to radiation damage. When used in combination with radiation, AuNPs enhance the rate of cell killing; hence, they may be of great value in radiotherapy. This study assessed the effects of radiation and AuNPs on mitochondrial reactive oxygen species (ROS) generation in cancer cells as an adjunct therapeutic target in addition to the DNA of the cell. Mitochondria are considered one of the primary sources of cellular ROS. High levels of ROS can result in an intracellular state of oxidative stress, leading to permanent cell damage. In this study, human melanoma and prostate cancer cell lines, with and without AuNPs, were irradiated with 6-Megavolt X-rays at doses of 0–8 Gy. Indicators of mitochondrial stress were quantified using two techniques, and were found to be significantly increased by the inclusion of AuNPs in both cell lines. Radiobiological damage to mitochondria was quantified via increased ROS activity. The ROS production by mitochondria in cells was enhanced by the inclusion of AuNPs, peaking at ~4 Gy and then decreasing at higher doses. This increased mitochondrial stress may lead to more effectively kill of AuNP-treated cells, further enhancing the applicability of functionally-guided nanoparticles.     

A multiple lateral flow immunoassay based on AuNP for the detection of 5 chemical contaminants in milk

Melamine (MEL), enrofloxacin (ENR), sulfamethazine (SMZ), tetracycline (TC), and aflatoxin M₁ (AFM₁) are the main chemical contaminants in milk. It is necessary to detect these miscellaneous chemical contaminants in milk synchronously to ensure the safety of the milk. In this study, a multiple lateral flow immunoassay (LFIA) was developed for the detection of MEL, ENR, SMZ, TC, and AFM₁ in milk. Under optimal experimental conditions, the cutoff values were 25 ng/mL for MEL, 1 ng/mL for ENR, 2.5 ng/mL for SMZ, 2.5 ng/mL for TC, and 0.25 ng/mL for AFM₁ in milk samples. The limits of detection of LFIA were 0.173 ng/mL for MEL, 0.078 ng/mL for ENR, 0.059 ng/mL for SMZ, 0.082 ng/mL for TC, and 0.0064 ng/mL for AFM₁. The recovery rates of LFIA in milk were 83.2–104.4% for MEL, 76.5–127.3% for ENR, 96.8–113.5% for SMZ, 107.1–166.6% for TC, and 93.5–130.3% for AFM₁. The coefficients of variation were all less than 15%. As a whole, the developed multiple lateral flow immunoassay showed potential as a highly reliable and excellent tool for the rapid and sensitive screening of MEL, ENR, SMZ, TC, and AFM₁ in milk.