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19 pages, 4227 KiB

Open AccessArticle

Microparticles vs. Macroparticles as Curcumin Delivery Vehicles: Structural Studies and Cytotoxic Effect in Human Adenocarcinoma Cell Line (LoVo)

by Joanna Wezgowiec, Marta Tsirigotis-Maniecka, Jolanta Saczko, Mieszko Wieckiewicz and Kazimiera A. Wilk

Molecules 2021, 26(19), 6056; https://doi.org/10.3390/molecules26196056 - 6 Oct 2021

Cited by 11 | Viewed by 2294

Abstract

This study aimed to characterize the hydrogel micro- and macro-particles designed to deliver curcumin to human colon cancer cells (LoVo). Six series of vehicles based on sodium alginate (micro- and macro-particles, uncoated, coated with chitosan or gelatin) were synthesized. The uncoated microparticles were [...] Read more.

This study aimed to characterize the hydrogel micro- and macro-particles designed to deliver curcumin to human colon cancer cells (LoVo). Six series of vehicles based on sodium alginate (micro- and macro-particles, uncoated, coated with chitosan or gelatin) were synthesized. The uncoated microparticles were fabricated using an emulsion-based technique and the uncoated macroparticles with an extrusion technique, with both coupled with ionotropic gelation. The surface morphology of the particles was examined with scanning electron microscopy and the average size was measured. The encapsulation efficiency, moisture content, and swelling index were calculated. The release of curcumin from the particles was studied in an experiment simulating the conditions of the stomach, intestine, and colon. To evaluate the anticancer properties of such targeted drug delivery systems, the cytotoxicity of both curcumin-loaded and unloaded carriers to human colon cancer cells was assessed. The microparticles encapsulated much less of the payload than the macroparticles and released their content in a more prolonged manner. The unloaded carriers were not cytotoxic to LoVo cells, while the curcumin-loaded vehicles impaired their viability—more significantly after incubation with microparticles compared to macroparticles. Gelatin-coated or uncoated microparticles were the most promising carriers but their potential anticancer activity requires further thorough investigation. Full article

(This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug Delivery)

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11 pages, 2140 KiB

Open AccessArticle

The Evidence of the Bystander Effect after Bleomycin Electrotransfer and Irreversible Electroporation

by Paulius Ruzgys, Neringa Barauskaitė, Vitalij Novickij, Jurij Novickij and Saulius Šatkauskas

Molecules 2021, 26(19), 6001; https://doi.org/10.3390/molecules26196001 - 2 Oct 2021

Cited by 6 | Viewed by 2356

Abstract

One of current applications of electroporation is electrochemotherapy and electroablation for local cancer treatment. Both of these electroporation modalities share some similarities with radiation therapy, one of which could be the bystander effect. In this study, we aimed to investigate the role of [...] Read more.

One of current applications of electroporation is electrochemotherapy and electroablation for local cancer treatment. Both of these electroporation modalities share some similarities with radiation therapy, one of which could be the bystander effect. In this study, we aimed to investigate the role of the bystander effect following these electroporation-based treatments. During direct CHO-K1 cell treatment, cells were electroporated using one 100 µs duration square wave electric pulse at 1400 V/cm (for bleomycin electrotransfer) or 2800 V/cm (for irreversible electroporation). To evaluate the bystander effect, the medium was taken from directly treated cells after 24 h incubation and applied on unaffected cells. Six days after the treatment, cell viability and colony sizes were evaluated using the cell colony formation assay. The results showed that the bystander effect after bleomycin electrotransfer had a strong negative impact on cell viability and cell colony size, which decreased to 2.8% and 23.1%, respectively. On the contrary, irreversible electroporation induced a strong positive bystander effect on cell viability, which increased to 149.3%. In conclusion, the results presented may serve as a platform for further analysis of the bystander effect after electroporation-based therapies and may ultimately lead to refined application of these therapies in clinics. Full article

(This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug Delivery)

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17 pages, 3640 KiB

Open AccessArticle

Oxidative Effects during Irreversible Electroporation of Melanoma Cells—In Vitro Study

by Wojciech Szlasa, Aleksander Kiełbik, Anna Szewczyk, Nina Rembiałkowska, Vitalij Novickij, Mounir Tarek, Jolanta Saczko and Julita Kulbacka

Molecules 2021, 26(1), 154; https://doi.org/10.3390/molecules26010154 - 31 Dec 2020

Cited by 33 | Viewed by 4549

Abstract

Irreversible electroporation (IRE) is today used as an alternative to surgery for the excision of cancer lesions. This study aimed to investigate the oxidative and cytotoxic effects the cells undergo during irreversible electroporation using IRE protocols. To do so, we used IRE-inducing pulsed [...] Read more.

Irreversible electroporation (IRE) is today used as an alternative to surgery for the excision of cancer lesions. This study aimed to investigate the oxidative and cytotoxic effects the cells undergo during irreversible electroporation using IRE protocols. To do so, we used IRE-inducing pulsed electric fields (PEFs) (eight pulses of 0.1 ms duration and 2–4 kV/cm intensity) and compared their effects to those of PEFs of intensities below the electroporation threshold (eight pulses, 0.1 ms, 0.2–0.4 kV/cm) and the PEFs involving elongated pulses (eight pulses, 10 ms, 0.2–0.4 kV/cm). Next, to follow the morphology of the melanoma cell membranes after treatment with the PEFs, we analyzed the permeability and integrity of their membranes and analyzed the radical oxygen species (ROS) bursts and the membrane lipids’ oxidation. Our data showed that IRE-induced high cytotoxic effect is associated both with irreversible cell membrane disruption and ROS-associated oxidation, which is occurrent also in the low electric field range. It was shown that the viability of melanoma cells characterized by similar ROS content and lipid membrane oxidation after PEF treatment depends on the integrity of the membrane system. Namely, when the effects of the PEF on the membrane are reversible, aside from the high level of ROS and membrane oxidation, the cell does not undergo cell death. Full article

(This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug Delivery)

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19 pages, 4178 KiB

Open AccessArticle

In Vitro Study of Calcium Microsecond Electroporation of Prostate Adenocarcinoma Cells

by Aleksander Kiełbik, Wojciech Szlasa, Olga Michel, Anna Szewczyk, Mounir Tarek, Jolanta Saczko and Julita Kulbacka

Molecules 2020, 25(22), 5406; https://doi.org/10.3390/molecules25225406 - 19 Nov 2020

Cited by 15 | Viewed by 3633

Abstract

Electroporation, applied as a non-thermal ablation method has proven to be effective for focal prostate treatment. In this study, we performed pre-clinical research, which aims at exploring the specific impact of this so-called calcium electroporation on prostate cancer. First, in an in-vitro study [...] Read more.

Electroporation, applied as a non-thermal ablation method has proven to be effective for focal prostate treatment. In this study, we performed pre-clinical research, which aims at exploring the specific impact of this so-called calcium electroporation on prostate cancer. First, in an in-vitro study of DU 145 cell lines, microsecond electroporation (μsEP) parameters were optimized. We determined hence the voltage that provides both high permeability and viability of these prostate cancer cells. Subsequently, we compared the effect of μsEP on cells’ viability with and without calcium administration. For high-voltage pulses, the cell death’s mechanism was evaluated using flow-cytometry and confocal laser microscopy. For lower-voltage pulses, the influence of electroporation on prostate cancer cell mobility was studied using scratch assays. Additionally, we applied calcium-binding fluorescence dye (Fluo-8) to observe the calcium uptake dynamic with the fluorescence microscopy. Moreover, the molecular dynamics simulation visualized the process of calcium ions inflow during μsEP. According to our results calcium electroporation significantly decreases the cells viability by promoting apoptosis. Furthermore, our data shows that the application of pulsed electric fields disassembles the actin cytoskeleton and influences the prostate cancer cells’ mobility. Full article

(This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug Delivery)

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15 pages, 3211 KiB

Open AccessFeature PaperArticle

Effect of Interaction between 17β-Estradiol, 2-Methoxyestradiol and 16α-Hydroxyestrone with Chromium (VI) on Ovary Cancer Line SKOV-3: Preliminary Study

by Ewa Sawicka, Jolanta Saczko, Joanna Roik, Julita Kulbacka and Agnieszka Piwowar

Molecules 2020, 25(21), 5214; https://doi.org/10.3390/molecules25215214 - 9 Nov 2020

Cited by 5 | Viewed by 2615

Abstract

Ovarian cancer is the leading cause of death from gynecologic malignancies. Some estrogens, as well as xenoestrogens, such as chromium (VI) (Cr(VI)), are indicated as important pathogenic agents. The objective of this study was to evaluate the role of estradiol and some its [...] Read more.

Ovarian cancer is the leading cause of death from gynecologic malignancies. Some estrogens, as well as xenoestrogens, such as chromium (VI) (Cr(VI)), are indicated as important pathogenic agents. The objective of this study was to evaluate the role of estradiol and some its metabolites upon exposure to the metalloestrogen Cr(VI) in an in vitro model. The changes in cell viability of malignant ovarian cancer cells (SKOV-3 resistant to cisplatin) exposed to 17β-estradiol (E2) and its two metabolites, 2-methoxyestradiol (2-MeOE2) and 16α-hydroxyestrone (16α-OHE1), upon exposure to potassium chromate (VI) and its interactions were examined. The single and mixed models of action, during short and long times of incubation with estrogens, were applied. The different effects (synergism and antagonism) of estrogens on cell viability in the presence of Cr(VI) was observed. E2 and 16α-OHE1 caused a synergistic effect after exposure to Cr(VI). 2-MeOE2 showed an antagonistic effect on Cr(VI). The examined estrogens could be ranked according to the most protective effect or least toxicity in the order: 2-MeOE2 > E2 > 16α-OHE1. Early pre-incubation (24 h or 7 days) of cells with estrogens caused mostly an antagonistic effect—protective against the toxic action of Cr(VI). The beneficial action of estrogens on the toxic effect of Cr(VI), in the context of the risk of ovarian cancer, seems to be important and further studies are needed. Full article

(This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug Delivery)

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12 pages, 2042 KiB

Open AccessArticle

Electrochemotherapy Using Doxorubicin and Nanosecond Electric Field Pulses: A Pilot in Vivo Study

by Vitalij Novickij, Veronika Malyško, Augustinas Želvys, Austėja Balevičiūtė, Auksė Zinkevičienė, Jurij Novickij and Irutė Girkontaitė

Molecules 2020, 25(20), 4601; https://doi.org/10.3390/molecules25204601 - 9 Oct 2020

Cited by 18 | Viewed by 3119

Abstract

Pulsed electric field (PEF) is frequently used for intertumoral drug delivery resulting in a well-known anticancer treatment—electrochemotherapy. However, electrochemotherapy is associated with microsecond range of electrical pulses, while nanosecond range electrochemotherapy is almost non-existent. In this work, we analyzed the feasibility of nanosecond [...] Read more.

Pulsed electric field (PEF) is frequently used for intertumoral drug delivery resulting in a well-known anticancer treatment—electrochemotherapy. However, electrochemotherapy is associated with microsecond range of electrical pulses, while nanosecond range electrochemotherapy is almost non-existent. In this work, we analyzed the feasibility of nanosecond range pulse bursts for successful doxorubicin-based electrochemotherapy in vivo. The conventional microsecond (1.4 kV/cm × 100 µs × 8) procedure was compared to the nanosecond (3.5 kV/cm × 800 ns × 250) non-thermal PEF-based treatment. As a model, Sp2/0 tumors were developed. Additionally, basic current and voltage measurements were performed to detect the characteristic conductivity-dependent patterns and to serve as an indicator of successful tumor permeabilization both in the nano and microsecond pulse range. It was shown that nano-electrochemotherapy can be the logical evolution of the currently established European Standard Operating Procedures for Electrochemotherapy (ESOPE) protocols, offering better energy control and equivalent treatment efficacy. Full article

(This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug Delivery)

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Review

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34 pages, 894 KiB

Open AccessReview

Exosomes and Other Extracellular Vesicles with High Therapeutic Potential: Their Applications in Oncology, Neurology, and Dermatology

by Urszula Szwedowicz, Zofia Łapińska, Agnieszka Gajewska-Naryniecka and Anna Choromańska

Molecules 2022, 27(4), 1303; https://doi.org/10.3390/molecules27041303 - 15 Feb 2022

Cited by 24 | Viewed by 6804

Abstract

Until thirty years ago, it was believed that extracellular vesicles (EVs) were used to remove unnecessary compounds from the cell. Today, we know about their enormous potential in diagnosing and treating various diseases. EVs are essential mediators of intercellular communication, enabling the functional [...] Read more.

Until thirty years ago, it was believed that extracellular vesicles (EVs) were used to remove unnecessary compounds from the cell. Today, we know about their enormous potential in diagnosing and treating various diseases. EVs are essential mediators of intercellular communication, enabling the functional transfer of bioactive molecules from one cell to another. Compared to laboratory-created drug nanocarriers, they are stable in physiological conditions. Furthermore, they are less immunogenic and cytotoxic compared to polymerized vectors. Finally, EVs can transfer cargo to particular cells due to their membrane proteins and lipids, which can implement them to specific receptors in the target cells. Recently, new strategies to produce ad hoc exosomes have been devised. Cells delivering exosomes have been genetically engineered to overexpress particular macromolecules, or transformed to release exosomes with appropriate targeting molecules. In this way, we can say tailor-made therapeutic EVs are created. Nevertheless, there are significant difficulties to solve during the application of EVs as drug-delivery agents in the clinic. This review explores the diversity of EVs and the potential therapeutic options for exosomes as natural drug-delivery vehicles in oncology, neurology, and dermatology. It also reflects future challenges in clinical translation. Full article

(This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug Delivery)

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33 pages, 2280 KiB

Open AccessReview

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

by Anna Choromańska, Agnieszka Chwiłkowska, Julita Kulbacka, Dagmara Baczyńska, Nina Rembiałkowska, Anna Szewczyk, Olga Michel, Agnieszka Gajewska-Naryniecka, Dawid Przystupski and Jolanta Saczko

Molecules 2021, 26(7), 1850; https://doi.org/10.3390/molecules26071850 - 25 Mar 2021

Cited by 23 | Viewed by 6538

Abstract

Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., [...] Read more.

Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., pharmacological, physical, and mechanical. It is crucial to keep in mind the significance of drug resistance phenomenon, ion channel and specific receptor impact, and lipid bilayer organization in planning the cell membrane-targeted treatment. In this review, strategies based on cell membrane modulation or reorganization are presented as an alternative tool for future therapeutic protocols. Full article

(This article belongs to the Special Issue Novel Physical and Chemical Methods for Facilitated Drug Delivery)

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