Dendrimer Platforms for Targeted Doxorubicin Delivery-Physicochemical Properties in Context of Biological Responses.

The unique structure of G4.0 PAMAM dendrimers allows a drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin hydrochloride (DOX) were optimized. The physicochemical properties of the system were monitored using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. The Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier's surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the Isothermal calorimetry (ITC) isotherm. Fluorescence spectra and release curves identified the reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of the G4.0-DOX complex was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is essential from a therapeutic point of view.

Alternations of NF-κB Signaling by Natural Compounds in Muscle-Derived Cancers.

The NF-κB-signaling pathway plays a crucial role in cancer progression, including muscle-derived cancers such as rhabdomyosarcoma or sarcoma. Several natural compounds have been studied for their ability to alter NF-κB signaling in these types of cancers. This review paper summarizes the current knowledge on the effects of natural compounds, including curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, and berberine, on NF-κB signaling in muscle-derived cancers. These compounds have been shown to inhibit NF-κB signaling in rhabdomyosarcoma cells through various mechanisms, such as inhibiting the activation of the IKK complex and the NF-κB transcription factor. These findings suggest that natural compounds could be potential therapeutic agents for muscle-derived cancers. However, further research is needed to fully understand their mechanisms of action and potential clinical applications.

Irreversible Electroporation in Pancreatic Cancer-An Evolving Experimental and Clinical Method.

Pancreatic cancer has no symptoms until the disease has advanced and is aggressive cancer with early metastasis. Up to now, the only curative treatment is surgical resection, which is possible in the early stages of the disease. Irreversible electroporation treatment offers new hope for patients with unresectable tumors. Irreversible electroporation (IRE) is a type of ablation therapy that has been explored as a potential treatment for pancreatic cancer. Ablation therapies involve the use of energy to destroy or damage cancer cells. IRE involves using high-voltage, low-energy electrical pulses to create resealing in the cell membrane, causing the cell to die. This review summarizes experiential and clinical findings in terms of the IRE applications. As was described, IRE can be a non-pharmacological approach (electroporation) or combined with anticancer drugs or standard treatment methods. The efficacy of irreversible electroporation (IRE) in eliminating pancreatic cancer cells has been demonstrated through both in vitro and in vivo studies, and it has been shown to induce an immune response. Nevertheless, further investigation is required to assess its effectiveness in human subjects and to comprehensively understand IRE's potential as a treatment option for pancreatic cancer.

Electroporation and Electrochemotherapy in Gynecological and Breast Cancer Treatment.

Gynecological carcinomas affect an increasing number of women and are associated with poor prognosis. The gold standard treatment plan is mainly based on surgical resection and subsequent chemotherapy with cisplatin, 5-fluorouracil, anthracyclines, or taxanes. Unfortunately, this treatment is becoming less effective and is associated with many side effects that negatively affect patients' physical and mental well-being. Electroporation based on tumor exposure to electric pulses enables reduction in cytotoxic drugs dose while increasing their effectiveness. EP-based treatment methods have received more and more interest in recent years and are the subject of a large number of scientific studies. Some of them show promising therapeutic potential without using any cytotoxic drugs or molecules already present in the human body (e.g., calcium electroporation). This literature review aims to present the fundamental mechanisms responsible for the course of EP-based therapies and the current state of knowledge in the field of their application in the treatment of gynecological neoplasms.

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

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.

Evaluation of Wound Healing Activity of Salvianolic Acid B on In Vitro Experimental Model.

Despite a wide range of bactericides and antiseptics, the treatment of chronic or complicated wounds is still a major challenge for modern medicine. Topical medications are the most sought-after new agents for use as treatment. The therapeutic concentration of their active substances is easy to achieve with the lowest possible burden on the patient's body. This study assesses the effect of salvianolic acid B (Sal B) on the proliferation, migration, and production of collagen type III by fibroblasts, which are the most important processes in wound healing. The study was conducted on human gingival fibroblasts obtained from primary cell culture. The results showed that Sal B at a dose of 75 µg/mL increases the cell viability with significant stimulation of the cell migration as demonstrated in the wound healing assay, as well as an increase in the expression of collagen type III, which has great importance in the initial stages of wound scarring. The results obtained in the conducted studies and previous scientific reports on the antibacterial properties and low toxicity of Sal B indicate its high potential in wound healing.

Electroporation-derived melanoma extracellular particles activate fibroblasts.

Although the pulse electric field (PEF) has been used in electrochemotherapy (ECT) for many years, the kinetics and profile of extracellular particles (EPs) released as a result of reversible electroporation have yet to be studied. It also needs to be clarified whether and how the profile of released EPs depends on the parameters of the applied PEF. The presented studies investigated the effect of EPs released from human melanoma cells after various parameters of reversible electroporation on markers indicating EP-mediated transformation of normal fibroblasts into tumor-associated fibroblasts. The expression levels of the vascular cell adhesion molecule-1 (VCAM-1) and changes in the expression of phosphor-histone H3 (pHH3), a biomarker specific for cells in mitosis, cell viability, and the migration capacity of the studied fibroblast cells, were analyzed. EPs were isolated from two commercial malignant melanoma cell lines previously subjected to reversible electroporation. Human primary fibroblasts (HPFs) were selected for EPs exposure. It was observed that after incubation with melanoma-derived EPs, HPFs showed differences in cell viability, migration capacity, VCAM-1, pHH3, and N-cadherin expression, depending on PEF parameters and the grade of melanoma cells. This study highlights that small extracellular particles (sEPs) from cancer cells can promote metastasis by carrying specific signals that lead to the upregulation of molecules like FAK, MMP-9, and N-cadherin in recipient cells.

Electrochemotherapy of melanoma: What we know and what is unexplored?

The cell membrane can be permeabilized when subjected to calibrated short electric pulses. This membrane alteration can be reversible, leaving cell viability unaffected. This set of events is called electroporation (EP). It is now used in clinical applications to introduce hydrophilic drugs into the cytoplasm. One of the EP applications is electrochemotherapy (ECT), in which EP is used for the selective delivery of drugs administered to treat cancer. The combination of EP with chemotherapy allows local cancer treatment, lowering the drug dose and reducing the side effects of systemic chemotherapy. Nowadays, bleomycin-based ECT (BLM-ECT) is a safe treatment for cutaneous tumors and skin metastases with established standard operating procedures. Additionally, there is emerging evidence that BLM-ECT may be particularly effective in combination with immunotherapies, acting synergistically and producing enhanced systemic anti-tumor effects. Still, to make it the first-choice therapy in patients with metastatic melanoma, further studies are needed to establish the relative effectiveness of ECT. Analyzing the EP phenomenon and the objective complexity of the associated effects at the cell level, we came across a problem that has not yet been investigated in increasing the therapeutic effectiveness of ECT. The profile and kinetics of extracellular vesicles (EVs) released from cells subjected to EP have not been analyzed. The exact nature of these EVs is unknown.

Impact of APRF+ in Combination with Autogenous Fibroblasts on Release Growth Factors, Collagen, and Proliferation and Migration of Gingival Fibroblasts: An In Vitro Study.

The present study aimed to compare the action of advanced platelet-rich fibrin (A-PRF+) alone with the action of A-PRF+ combined with autologous gingival fibroblasts. The components released from A-PRF+ conditioned with autogenous fibroblasts that were quantified in the study were fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), trans-forming growth factor-beta1 and 2 (TGFß1 and TGFß2), and soluble collagen. A-PRF+ combined with fibroblasts demonstrated significantly higher values of released VEGF at every time point and, after 7 days, significantly higher values of released TGFß2. A viability test after 72 h showed a significant increase in proliferation fibroblasts after exposition to the factors released from A-PRF+ combined with fibroblasts. Similarly, the degree of wound closure after 48 h was significantly higher for the factors released from A-RRF+ alone and the factors released from A-RRF+ combined with fibroblasts. These results imply that platelet-rich fibrin (PRF) enhanced with fibroblasts can be an alternative method of connective tissue transplantation.