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(a) UV–vis absorption spectra of DOX; (b) UV–vis absorption spectra of EPI; (c) UV–vis absorption spectra of MIT. Conditions: DOX, 18 μg mL −1 ; EPI, 12 μg mL −1 ; MIT, 9.0 μg mL −1 ; PTX, 18 μg mL −1 ; ctDNA, 2.0 μg mL −1 ; pH 7.4
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We have developed a method to investigate the interaction between DNA-targeted anthracyclines and DNA in the presence of the drug paclitaxel. It is based on resonance light scattering (RLS) and on the finding that anthracyclines when bound to DNA undergo a dramatic enhancement in their RLS intensities, while paclitaxel does not display such an effe...
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Citations
... It was found that the binding of taxane to serum albumin can occur near the binding sites of DOX to serum albumin, and can induce surrounding conformation changes of serum albumin [28]. Chen et al. have found that taxane can significantly enhance the resonance light scattering (RLS) signal and improve the binding ability of anthracyclines to DNA using RLS technique [29]. Zeng et al. have demonstrated that DOX can interfere with the cytotoxic effect of DOC on both mitotic arrest and apoptotic cell death through DNA fragmentation analyses, flow cytometry and cell rotation analysis [30]. ...
Docetaxel (DOC) is one of the second-generation antineoplastic drugs of the taxanes family with excellent antitumor activity. However, the mechanism of DOC inducing tumor cell apoptosis and treating cancer diseases, especially its interaction with DNA in the nucleus, and its adjuvant or combined Doxorubicin (DOX) acting on DNA molecules are unclear. In this study, the interaction mechanism between DOC and DNA, as well as the synergistic effects and competitive relationships among DOC and DOX when they simultaneously interact with DNA molecules were studied by laser confocal Raman spectroscopy combined with UV–visible absorption spectroscopy and molecular docking technology. The spectroscopic results showed that the binding constant of DOC to DNA is 5.25 × 10³ M⁻¹, the binding modes of DOC and DNA are non-classical intercalation and electrostatic binding, and the DNA-DOC complex has good stability. When DOC or DOX interacts with DNA alone, both of them can bind with bases and phosphate backbone of DNA, and also lead to DNA conformation changes; when DOC and DOX interact with DNA at the same time, the orders of interaction not only affect their binding sites with DNA, but also cause changes in the surrounding environment of the binding sites. In addition, the molecular docking results further verified that DOC and DOX have synergy and competition when they interact with DNA molecules simultaneously. The docking energies of DNA-DOC and DNA-DOX indicate the important role of van der Waals forces and hydrogen bonds. This study has practical significance for the design and development of antitumor drugs with less toxic based on the taxanes family and the combination with other drugs for the treatment of cancer.
... However, targeting and understanding the mechanism of drug interactions with DNA are still elusive and pose significant challenges in the drug discovery pipeline [4]. A wide range of organic compounds, such as the class of molecules known as DNA intercalating agents, have been studied for several decades, and a few examples, such as ellipticine, anthracycline, acridine, and anthraquinone, are routinely used in the treatment of cancer [5][6][7][8][9]. Thiosemicarbazones are recognized to have broadspectrum antiviral activity against various DNA and RNA viruses and are considered a potential prophylactic therapy for human diseases [10]. ...
... DOX'un DNA ile etkileşiminden sonraki absorpsiyon spektrumuna bakıldığında ise (Şekil 5.c), 483 nm'de bulunan maksimum DOX absorpsiyonunda hipokromik etki olduğu gözlendi. Bu sonuç ilaç molekülleri ve DNA bazları arasında π-π istifleme etkileşimleri olduğunu gösterdi [30]. İnterkalasyon, bitişik baz çiftleri arasındaki ayrılmada bir artışı ve çift sarmalın kısmen çözülmesini içerir. ...
Bu çalışmada, nano-elektrokimyasal biyosensörler kullanılarak çift sarmallı deoksiribonükleik asit (dsDNA) ve doksorubisin (DOX) arasındaki etkileşim diferansiyel puls voltametrisi yöntemiyle araştırılmıştır. Biyosensör yüzeyi setil trimetilamonyum (sab) ve karbon nanotüp (knt) içeren çözeltiden elektrodepozisyon yöntemiyle poli(sab)-knt sentezi ile hazırlanmıştır. DNA-ilaç etkileşimi araştırmak için indikatör olarak dsDNA elektroaktif bazların voltametrik sinyalleri kullanılmıştır. İlaç-DNA etkileşimi sonrası hem guanin hem de adenin bazlarının oksidasyon pik akımlarının azaldığı gözlenmiştir. İlacın bağlanma süresi ve derişiminin dsDNA bazlarının voltametrik sinyalleri üzerindeki etkisi de değerlendirilmiştir. DOX için doğrusal çalışma aralığı 0,39-25 µg mL-1 arasında ve gözlenebilme sınırı 0,26 µg mL-1 olarak bulunmuştur. Elektrokimyasal ve spektrokimyasal çalışmalar, DOX ve dsDNA arasındaki etkileşim mekanizmasının interkalasyon modu ile gerçekleştiğini göstermiştir.
... In addition to the decrease of absorbance at 420 nm for porphyrin, a 4 nm shift of λmax to a longer wavelength was also observed. This slight bathochromic shift is possibly due to π-π stacking interactions between DOX and PGL [32]. The fluorescence spectra of PGL NPs and PGL-DOX NPs were also recorded at an excitation wavelength of 420 nm for porphyrin and 480 nm for DOX. ...
The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms. Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects. However, the challenges imposed by limited drug loading capacity and complex synthesis process of organic nanoparticles (NPs) have seriously impeded advances in chemo-photodynamic combination therapy.
license In this experiment, we utilize our previously
synthesized porphyrin-grafted lipid (PGL) NPs to load highly effective chemotherapeutic drug, doxorubicin (DOX) for synergistic chemo-photodynamic therapy. Methods: A relatively simple and inexpensive rapid injection method was used to prepare porphyrin-grafted lipid (PGL) NPs. The self-assembled PGL NPs were used further to encapsulate DOX via a pH-gradient loading protocol. The self-assembled liposome-like PGL NPs having a hydrophilic core were optimized to load DOX at an encapsulation efficiency (EE) of ~99%. The resultant PGL-DOX NPs were intact, highly stable and importantly these NPs successfully escaped from the endo-lysosomal compartment after laser irradiation to release DOX in the cytosol. The therapeutic efficacy of the aforementioned formulation was validated both in vitro and in vivo. Results: PGL-DOX NPs demonstrated excellent cellular uptake, chemo-photodynamic response, and fluorescence imaging ability in different cell lines. Under laser irradiation, cells treated with a low molar concentration of PGL-DOX NPs reduced cell
viability significantly. Moreover, in vivo
experiments conducted in a xenograft mouse model further demonstrated the excellent tumor accumulation capability of PGL-DOX NPs driven by the enhanced permeability and retention (EPR) effect. Through fluorescence imaging, the biodistribution of PGL-DOX NPs in tumor and major organs was also easily monitored in real time in vivo. The inherent ability of porphyrin to generate ROS under laser irradiation combined with the cytotoxic effect of the anticancer drug DOX significantly suppressed tumor growth in vivo. Conclusion: In summary, the PGL-DOX NPs combined chemo-photodynamic nanoplatform may serve as a potential candidate for cancer theranostics.
Through the incorporation of spectorescopic and molecular methods of modeling, the researchers investigated the interaction between Carbon Nanotubes (CNTs) and Human Serum Albumin (HSA). Fluorescence spectroscopy revealed the ability in both single-wall and multi-wall CNTs to quench the spectrum through a static quenching procedure obtained from the Stern–Volmer quenching constant (Ksv) at three different temperatures. The Ksv values of HSA–CNTs complexes were 1.96 × 10⁵ M⁻¹ and 2.44 × 10⁵ M⁻¹ that showed two different behaviors of interaction between HSA and CNTs. The Van’t Hoff equation was used to calculate thermodynamic parameters of Gibbs free energy (ΔG°), entropy (ΔS°) and enthalpy changes (ΔH°). The binding distances (r) between the donor (Trp residue of HSA) and acceptor (CNTs) was measured through the Förster theory of non-radiative energy transfer, and it was found to be less than 7 nm. The conformational changes of protein in the presence of CNTs were revealed through synchronous fluorescence spectra and three-dimensional fluorescence spectra analysis. The experimental results were confirmed through molecular modeling technique. Circular dichroism technique showed the secondary structure changes of HSA upon interaction with CNTs. The complex formation of HSA and CNTs was determined by the measurement of the electric conductivity. The molecular modeling technique determined the binding site of CNTs that were embedded in the subdomain IIIB of HSA. These analyses play a major role in drug delivery and pharmacodynamics studies for better understanding of nanotechnology levels.
Although numerous methods have been reported for the analysis of creatinine in human serum, the development of a simple, rapid, and practical sensor still remains a great challenge. In this work, a hierarchical colorimetric sensor was demonstrated based on the anti-aggregation effect of glutathione (GSH)-protected gold nanoparticles (AuNPs). Creatinine molecule could induce the aggregation of AuNPs, and the system could show blue color simultaneously. When GSH was added to incubate with AuNPs in advance, the solution could perform a hierarchical color change corresponding to different concentration of creatinine. Consequently, the change of AuNPs in size resulted in the difference of resonance light scattering (RLS) intensity and the quantitative detection of creatinine could be achieved. Meanwhile, the determination of creatinine in human serum could be attained with a detection limit of 1.21 μM, and the colorimetric sensor could be applied to detect creatinine in human serum successfully in a wide range from 10 to 1000 μM. As above, the creatinine in human serum could be distinguished using proper concentration of GSH. More practically, we could identify if the sample exceeded or below the critical value with our naked eye. This sensing proposal was accompanied with prominent simplicity, speediness, and practicability clinically.
A series of hyperbranched glycogen derivatives conjugated with different contents of cationic 3-(dimethylamino)-1-propylamine residues, named DMAPA-Glyp derivatives, were synthesized at room temperature. Resonance light scattering (RLS) spectroscopy was used to investigate the complexation behavior and efficacy of the DMAPA-Glyp derivatives and plasmid DNA (pDNA). Results indicated that the DMAPA-Glyp derivatives and pDNA molecules began to aggregate and form complexes at a weight ratio of two. Following further increases in the DMAPA-Glyp derivatives (w/w > 2), pDNA was condensed to form compact complexes. RLS spectroscopy is thus a useful tool for studying the complexation behavior and efficacy of cationic polymers with nucleic acid molecules. Circular dichroism analysis further revealed that the conformation of pDNA transformed from B-form to C-form and A-form during the complexation process.
The electrochemical behavior of calcein (CA) has been investigated by using a conductive carbon black paste electrode (CCBPE) as working electrode. It exhibits a single well‐defined redox peak in phosphate buffered saline in the range of pH 5.5–8.0, which attributes to the irreversible oxidation with 2 electrons and 2 protons participation. Under the optimized analytical conditions, the proposed linear sweep voltammetry (LSV) method allows the determination of CA in a linear concentration range of 0.64–9.60 µM, with a limit of detection of 0.32 µM. Further, the interaction between CA and DNA were studied by voltammetric and spectrometric methods. Both studies have shown that CA can bind to DNA by the intercalation binding mode. Under the present experimental condition, the binding constant β of CA and dsDNA is 1.10×107. Meanwhile, in the loop‐mediated isothermal amplification (LAMP) reaction mixture there is obvious interaction between CA and dsDNA, resulting in a nonignorable decrease of the indicating sensitivity.
We have developed a highly selective DNA biosensor. It was based on the long-range electron transfer (LRET) from the electroactive dye indigo carmine (IC) through the DNA duplex on a glassy carbon electrode. Voltammetric experiments showed that IC interacts with dsDNA through a typical intercalative mode with a relatively strong affinity of 2.3(±0.6) × 106 M-1. If incubated with DNA in IC solution, no response was observed with the ssDNA-modified probe electrode. However, a pair of well-defined redox peak was observed with a DNA-hybridized electrode, proving the presence of LRET on the biosensor. The biosensor also can differentiate complementary sequences, non-complementary sequences, and even the mutated sequences with single-base mismatches at different sites.
Figure
A highly selective DNA biosensor was developed based on the long-range electron transfer (LRET) of an electroactive indigo dye, indigo carmine through DNA duplex
The assay for alpha-fetoprotein (AFP) is based on the use of immobilized anti-AFP labeled with silver nanoparticles (AgNPs). The immunoreaction between the labeled antibody against AFP and free AFP takes place in pH 6.0 solution and leads to the formation of the respective immunocomplex which displays enhanced resonance light scattering (RLS) intensity at 480 nm. Under the optimal conditions, the intensity of the enhanced RLS is proportional to the concentration of AFP in the range from 0.10 to 50 ng mL−1, with a detection limit of 40 pg mL−1. The characteristics of RLS, the immunocomplex, the immuno response, and the optimum conditions of the immunoreaction have been investigated. The concentration of AFP in 20 serum specimens was determined by the new assay, and results are consistent with those obtained with a commercially available ELISA kit.
Figure
A new resonance light scattering assay of AFP based on silver nanoparticle and immunoreaction was developed.
