Chasing Graphene-Based Anticancer Drugs: Where are We Now on the Biomedical Graphene Roadmap?

Katarzyna Uzdrowska,1 Narcyz Knap,1 Jacek Gulczynski,2 Alicja Kuban-Jankowska,1 Wiktoria Struck-Lewicka,3 Michal J Markuszewski,3 Tomasz Bączek,3 Ewa Izycka-Swieszewska,2 Magdalena Gorska-Ponikowska1 1Department of Medical Chemistry, Medical University of Gdansk, Gdansk, 80-211, Poland; 2Faculty of Health Sciences with the Institute of Maritime and Tropical Medicine, Medical University of Gdansk, Gdansk, 80-211, Poland; 3Faculty of Pharmacy, Medical University of Gdansk, Gdansk, 80-416, PolandCorrespondence: Magdalena Gorska-Ponikowska, Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St, Gdansk, 80-211, Poland, Tel +48 58 349 14 50, Fax +48 58 349 14 56, Email [email protected]: Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and possible surface functionalizations. In parallel, prototypic graphene-based devices have been developed to diagnose, imaging and track tumor growth in cancer patients. There is a growing number of reports on the use of graphene and its functionalized derivatives in the design of innovative drugs delivery systems, photothermal and photodynamic cancer therapy, and as a platform to combine multiple therapies. The aim of this review is to introduce the latest scientific achievements in the field of innovative composite graphene materials as potentially applied in cancer therapy. The “Technology and Innovation Roadmap” published in the Graphene Flagship indicates, that the first anti-cancer drugs using graphene and graphene-derived materials will have appeared on the market by 2030. However, it is necessary to broaden understanding of graphene-based material interactions with cellular metabolism and signaling at the functional level, as well as toxicity. The main aspects of further research should elucidate how treatment methods (e.g., photothermal therapy, photodynamic therapy, combination therapy) and the physicochemical properties of graphene materials influence their ability to modulate autophagy and kill cancer cells. Interestingly, recent scientific reports also prove that graphene nanocomposites modulate cancer cell death by inducing precise autophagy dysfunctions caused by lysosome damage. It turns out as well that developing photothermal oncological treatments, it should be taken into account that near-infrared-II radiation (1000– 1500 nm) is a better option than NIR-I (750– 1000 nm) because it can penetrate deeper into tissues due to less scattering at longer wavelengths radiation.Keywords: graphene-based materials, oncological therapies, cancer treatment, biomedical innovations, drugs delivery system

LC-TOF-MS data collected for 300 small molecules. XBridge Shield RP18 column.

Retention time data for 300 analytes

An Approach Based on HPLC-Fingerprint and Chemometrics to Quality Consistency Evaluation of Matricaria chamomilla L. Commercial Samples

Chamomile has been used as an herbal medication since ancient times and is still popular because it contains various bioactive phytochemicals that could provide therapeutic effects. In this study, a simple and reliable HPLC method was developed to evaluate the quality consistency of nineteen chamomile samples through establishing a chromatographic fingerprint, quantification of phenolic compounds and determination of antioxidant activity. For fingerprint analysis, 12 peaks were selected as the common peaks to evaluate the similarities of commercial samples of chamomile obtained from different manufacturers. A similarity analysis was performed to assess the similarity/dissimilarity of chamomile samples where values varied from 0.868 to 0.990 what indicating that samples from different manufacturers were consistent. Additionally, simultaneous quantification of five phenolic acids (gallic, caffeic, syringic, p-coumaric, ferulic) and four flavonoids (rutin, myricetin, quercetin and keampferol) was performed to interpret the quality consistency. In quantitative analysis, the nine individual phenolic compounds showed good regression (r > 0.9975). Inter- and intra-day precisions for all analysed compounds expressed as relative standard deviation (CV) ranged from 0.05% to 3.12%. Since flavonoids and other polyphenols are commonly recognised as natural antioxidants, the antioxidant activity of chamomile samples was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and ferric reducing/antioxidant power (FRAP) assay. Correlation analysis was used to assess the relationship between antioxidant activity and phenolic composition, and multivariate analysis (PCA and HCA) were applied to distinguish chamomile samples. Results shown in the study indicate high similarity of chamomile samples among them, widely spread in the market and commonly used by people as infusions or teas, as well as that there were no statistically significant differences among them, which in turn is a proof of high quality of commercially available samples of chamomile. The study indicated that the combination of chromatographic fingerprint and quantitative analysis can be readily utilised as a quality consistency method for chamomile and related medicinal preparations. Moreover, the applied strategy seems to be the most promising for the assessment of the investigated plant material

Effects of perineural administration of ropivacaine combined with perineural or intravenous administration of dexmedetomidine for sciatic and saphenous nerve blocks in dogs.

peer reviewedOBJECTIVE: To evaluate the effects of using ropivacaine combined with dexmedetomidine for sciatic and saphenous nerve blocks in dogs. ANIMALS: 7 healthy adult Beagles. PROCEDURES: In phase 1, dogs received each of the following 3 treatments in random order: perineural sciatic and saphenous nerve injections of 0.5% ropivacaine (0.4 mL/kg) mixed with saline (0.9% NaCl) solution (0.04 mL/kg; DEX0PN), 0.5% ropivacaine mixed with dexmedetomidine (1 μg/kg; DEX1PN), and 0.5% ropivacaine mixed with dexmedetomidine (2 μg/kg; DEX2PN). In phase 2, dogs received perineural sciatic and saphenous nerve injections of 0.5% ropivacaine and an IV injection of diluted dexmedetomidine (1 μg/kg; DEX1IV). For perineural injections, the dose was divided equally between the 2 sites. Duration of sensory blockade was evaluated, and plasma dexmedetomidine concentrations were measured. RESULTS: Duration of sensory blockade was significantly longer with DEX1PN and DEX2PN, compared with DEX0PN; DEX1IV did not prolong duration of sensory blockade, compared with DEX0PN. Peak plasma dexmedetomidine concentrations were reached after 15 minutes with DEX1PN (mean ± SD, 348 ± 200 pg/mL) and after 30 minutes DEX2PN (816 ± 607 pg/mL), and bioavailability was 54 ± 40% and 73 ± 43%, respectively. The highest plasma dexmedetomidine concentration was measured with DEX1IV (1,032 ± 415 pg/mL) 5 minutes after injection. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that perineural injection of 0.5% ropivacaine in combination with dexmedetomidine (1 μg/kg) for locoregional anesthesia in dogs seemed to balance the benefit of prolonging sensory nerve blockade while minimizing adverse effects