scholarly journals Synergistic Photothermal-Chemotherapy Based on the Use of Biomimetic Magnetic Nanoparticles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 625
Author(s):  
Ylenia Jabalera ◽  
Alberto Sola-Leyva ◽  
María P. Carrasco-Jiménez ◽  
Guillermo R. Iglesias ◽  
Concepcion Jimenez-Lopez

MamC-mediated biomimetic magnetic nanoparticles (BMNPs) have emerged as one of the most promising nanomaterials due to their magnetic features (superparamagnetic character and large magnetic moment per particle), their novel surface properties determined by MamC, their biocompatibility and their ability as magnetic hyperthermia agents. However, the current clinical application of magnetic hyperthermia is limited due to the fact that, in order to be able to reach an effective temperature at the target site, relatively high nanoparticle concentration, as well as high magnetic field strength and/or AC frequency are needed. In the present study, the potential of BMNPs to increase the temperature upon irradiation of a laser beam in the near infrared, at a wavelength at which tissues become partially transparent, is explored. Moreover, our results also demonstrate the synergy between photothermia and chemotherapy in terms of drug release and cytotoxicity, by using BMNPs functionalized with doxorubicin, and the effectiveness of this combination therapy against tumor cells in in vitro experiments. Therefore, the findings of the present study open the possibility of a novel, alternative approach to fight localized tumors.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1168
Author(s):  
Ylenia Jabalera ◽  
Alberto Sola-Leyva ◽  
Salvatore Calogero Gaglio ◽  
María P. Carrasco-Jiménez ◽  
Guillermo R. Iglesias ◽  
...  

The synergy between directed chemotherapy and thermal therapy (both magnetic hyperthermia and photothermia) mediated by a nanoassembly composed of functionalized biomimetic magnetic nanoparticles (BMNPs) with the chemotherapeutic drug doxorubicin (DOXO) covered by the polymer poly(lactic-co-glycolic acid) (PLGA), decorated with TAT peptide (here referred to as TAT–PLGA(DOXO-BMNPs)) is explored in the present study. The rationale behind this nanoassembly lies in an optimization of the nanoformulation DOXO-BMNPs, already demonstrated to be more efficient against tumor cells, both in vitro and in vivo, than systemic traditional therapies. By embedding DOXO-BMNPs into PLGA, which is further functionalized with the cell-penetrating TAT peptide, the resulting nanoassembly is able to mediate drug transport (using DOXO as a drug model) and behaves as a hyperthermic agent (induced by an alternating magnetic field (AMF) or by laser irradiation with a laser power density of 2 W/cm2). Our results obtained using the HepG2 cell line show that there is a synergy between chemotherapy and thermal therapy that results in a stronger cytotoxic effect when compared to that caused by the soluble DOXO. This is probably due to the enhanced DOXO release occurring upon the application of the thermal therapy, as well as the induced local temperature rise mediated by BMNPs in the nanoassembly following exposition to AMF or to near-infrared (NIR) laser irradiation. These results represent a proof of concept demonstrating that TAT–PLGA(DOXO-BMNPs) can be used to efficiently combine therapies against tumor cells, which is a step forward in the transition from systemic to local treatments.


2021 ◽  
Vol 5 (3) ◽  
pp. 178-188
Author(s):  
Svitlana Gorobets ◽  
Nina Ilchuk ◽  
Iryna Demianenko ◽  
Maria Bannikova

Background. Nanomaterials are easily modified and have unique characteristics associated with a large reactive surface Due to these properties, nanomaterials are used in various branches of sciences and technology, such as pharmaceuticals, biotechnology, chemical technology, etc. Recently, the effect of magnetite nanoparticles on the morphological properties of plants has been actively studied for their further use as nanoadditives to increase yields and improve the properties of agricultural plants. Tobacco (Nicotiana tabacum) is a model object of plant biotechnology, it is used to study the effect of various factors on dicotyledonous plants, so it was chosen to study the effect of magnetite on the growth, development, and mass accumulation by plants. Objective. We are aimed to study the effect of magnetite nanoparticles on the growth and development of Nicotiana tabacum in vivo and in vitro. Methods. The ability of tobacco to produce biogenic magnetic nanoparticles by searching for mammal proteins homologues in theNicotiana tabacum proteome using the Blast NCBI program was studied using comparative genomics methods. The plants were divided into groups (control, magnetite nanoparticle concentration 0.1 mg/cm3, magnetite nanoparticle concentration 1 mg/cm3) for both in vivo and in vitro experiments. Analysis of plant parameters was performed every 14 days to study the dynamics of the effects of magnetite nanoparticles. Results. It was determined that magnetite nanoparticles at a concentration of 0.1 mg/cm3 in culture in vitro and in vivo significantly affect the growth of the root system and sprouts of Nicotiana tabacum. On the 56th day of plant cultivation in vitro on a salivary medium supplemented with magnetite nanoparticles at a concentration of 0.1 mg/cm3, an increase in the shoot length by 13.3%, root length by 31.7%, and the mass of absolutely dry substances by 18.75% was observed compared to the control. Treatment of magnetite nanoparticles with a suspension at a concentration of 0.1 mg/cm3 led to more pronounced results when growing tobacco in vivo. So, on the56th day, the root length increased by 23.3%, the length of the shoot – by 19.2%, and the mass of absolutely dry substances – by2 times, the first leaves appeared 2 days earlier compared to the control. The addition of magnetite nanoparticles to the substrate on which the plants were grown in vivo at a concentration of 1 mg/cm3 inhibits the growth of tobacco. Conclusions. Studies have shown the expediency of using magnetic nanoparticles at a concentration of 0.1 mg/cm3 as nanofertilizers in tobacco cultivation.


Author(s):  
J. Metuzals

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.


1997 ◽  
Vol 77 (05) ◽  
pp. 0920-0925 ◽  
Author(s):  
Bernd Pötzsch ◽  
Katharina Madlener ◽  
Christoph Seelig ◽  
Christian F Riess ◽  
Andreas Greinacher ◽  
...  

SummaryThe use of recombinant ® hirudin as an anticoagulant in performing extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices requires a specific and easy to handle monitoring system. The usefulness of the celite-induced activated clotting time (ACT) and the activated partial thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo blood samples obtained from eight patients treated with r-hirudin during open heart surgery. The very poor relationship between the prolongation of the ACT and APTT values and the concentration of r-hirudin as measured using a chromogenic factor Ila assay indicates that both assays are not suitable to monitor r-hirudin anticoagulation. As an alternative approach a whole blood clotting assay based on the prothrombin-activating snake venom ecarin has been tested. In vitro experiments using r-hirudin- spiked whole blood samples showed a linear relationship between the concentration of hirudin added and the prolongation of the clotting times up to a concentration of r-hirudin of 4.0 µg/ml. Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the accuracy of the ecarin clotting time (ECT) assay. Differences in the interindividual responsiveness to r-hirudin were analyzed on r-hirudin- spiked blood samples obtained from 50 healthy blood donors. CV- values between 1.8% and 6% measured at r-hirudin concentrations between 0.5 and 4 µg/ml indicate remarkably slight differences in r-hirudin responsiveness. ECT assay results of the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of r-hirudin. Moreover, assay results were not influenced by treatment with aprotinin or heparin. These findings together with the short measuring time with less than 120 seconds warrant the whole blood ECT to be a suitable assay for monitoring of r-hirudin anticoagulation in cardiac surgery.


2020 ◽  
Vol 16 (3) ◽  
pp. 392-402
Author(s):  
Christiaan W. van der Westhuyzen ◽  
Richard K. Haynes ◽  
Jenny-Lee Panayides ◽  
Ian Wiid ◽  
Christopher J. Parkinson

Background: With few exceptions, existing tuberculosis drugs were developed many years ago and resistance profiles have emerged. This has created a need for new drugs with discrete modes of action. There is evidence that tuberculosis (like other bacteria) is susceptible to oxidative pressure and this has yet to be properly utilised as a therapeutic approach in a manner similar to that which has proven highly successful in malaria therapy. Objective: To develop an alternative approach to the incorporation of bacterial siderophores that results in the creation of antitubercular peroxidic leads for subsequent development as novel agents against tuberculosis. Methods: Eight novel peroxides were prepared and the antitubercular activity (H37Rv) was compared to existing artemisinin derivatives in vitro. The potential for toxicity was evaluated against the L6 rat skeletal myoblast and HeLa cervical cancer lines in vitro. Results: The addition of a pyrimidinyl residue to an artemisinin or, preferably, a tetraoxane peroxidic structure results in antitubercular activity in vitro. The same effect is not observed in the absence of the pyrimidine or with other heteroaromatic substituents. Conclusion: The incorporation of a pyrimidinyl residue adjacent to the peroxidic function in an organic peroxide results in anti-tubercular activity in an otherwise inactive peroxidic compound. This will be a useful approach for creating oxidative drugs to target tuberculosis.


Chemistry ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 238-255
Author(s):  
Esther M. Sánchez-Carnerero ◽  
Marina Russo ◽  
Andreas Jakob ◽  
Lucie Muchová ◽  
Libor Vítek ◽  
...  

Carbon monoxide (CO) is an endogenously produced signaling molecule involved in the control of a vast array of physiological processes. One of the strategies to administer therapeutic amounts of CO is the precise spatial and temporal control over its release from photoactivatable CO-releasing molecules (photoCORMs). Here we present the synthesis and photophysical and photochemical properties of a small library of meso-carboxy BODIPY derivatives bearing different substituents at positions 2 and 6. We show that the nature of substituents has a major impact on both their photophysics and the efficiency of CO photorelease. CO was found to be efficiently released from π-extended 2,6-arylethynyl BODIPY derivatives possessing absorption spectra shifted to a more biologically desirable wavelength range. Selected photoCORMs were subjected to in vitro experiments that did not reveal any serious toxic effects, suggesting their potential for further biological research.


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