Cancer is one of the major causes of death worldwide and its treatment remains very challenging. The effectiveness of cancer therapy significantly depends upon tumour-specific delivery of the drug. Nanoparticle drug delivery systems have been developed to avoid the side effects of the conventional chemotherapy. However, according to the most recent recommendations, future nanomedicine should be focused mainly on active targeting of nanocarriers based on ligand-receptor recognition, which may show better efficacy than passive targeting in human cancer therapy. Nevertheless, the efficacy of single-ligand nanomedicines is still limited due to the complexity of the tumour microenvironment. Thus, the NPs are improved toward an additional functionality, e.g., pH-sensitivity (advanced single-targeted NPs). Moreover, dual-targeted nanoparticles which contain two different types of targeting agents on the same drug delivery system are developed. The advanced single-targeted NPs and dual-targeted nanocarriers present superior properties related to cell selectivity, cellular uptake and cytotoxicity toward cancer cells than conventional drug, non-targeted systems and single-targeted systems without additional functionality. Folic acid and biotin are used as targeting ligands for cancer chemotherapy, since they are available, inexpensive, nontoxic, nonimmunogenic and easy to modify. These ligands are used in both, single- and dual-targeted systems although the latter are still a novel approach. This review presents the recent achievements in the development of single- or dual-targeted nanoparticles for anticancer drug delivery.

Fluoroquinolone antibiotics induce cytotoxicity in various cancer cell lines and may therefore represent a potentially important source of novel anticancer agents. The aim of the present study was to examine the effect of ciprofloxacin on the viability, redox balance, apoptosis, expression of p53, Bax and Bcl-2, cell cycle distribution and DNA fragmentation of triple-negative MDA-MB-231 breast cancer cells. The results of the present study demonstrated that ciprofloxacin decreases cell viability in a dose- and time-dependent manner. The half maximal inhibitory concentration values of ciprofloxacin in MDA-MB-231 cells following treatment for 24, 48 and 72 h were 0.83, 0.14 and 0.03 µmol/ml, respectively. Furthermore, it was demonstrated that ciprofloxacin altered the redox signaling pathway, as determined by intracellular glutathione depletion. The results of Annexin V/propidium iodide staining revealed that ciprofloxacin triggered the apoptosis of MDA-MB-231 cells. Furthermore, cipfloxacin treatment stimulated the loss of the mitochondrial transmembrane potential via the Bax/Bcl-2-dependent pathway, thus inducing apoptosis. Ciprofloxacin induced cell cycle arrest at the S-phase; therefore it was hypothesized that ciprofloxacin inhibits topoisomerase II. Oligonucleosomal DNA fragmentation and the elevation of p53 expression were observed in the present study, indicating that this late-apoptotic event may be mediated by the p53-dependent pathway. Therefore, the results of the current study provide important molecular data concerning the cellular cascade, which may explain the cytotoxicity induced by ciprofloxacin in human triple-negative breast cancer cells, thus providing a novel insight into the therapeutic properties of this drug.

Background: A large body of research has focused on fluoroquinolones. It was shown that this class of synthetic antibiotics could possess antiviral activity as a broad range of anti-infective activities. Based on these findings, we have undertaken in silico molecular docking study to demonstrate, for the first time, the principle for the potential evidence pointing ciprofloxacin and moxifloxacin ability to interact with COVID-19 Main Protease. Methods: In silico molecular docking and molecular dynamics techniques were applied to assess the potential for ciprofloxacin and moxifloxacin interaction with COVID-19 Main Protease (M^pro). Chloroquine and nelfinavir were used as positive controls. Results: We revealed that the tested antibiotics exert strong capacity for binding to COVID-19 Main Protease (M^pro). According to the results obtained from the GOLD docking program, ciprofloxacin and moxifloxacin bind to the protein active site more strongly than the native ligand. When comparing with positive controls, a detailed analysis of the ligand–protein interactions shows that the tested fluoroquinolones exert a greater number of protein interactions than chloroquine and nelfinavir. Moreover, lower binding energy values obtained from K_DEEP program were stated when compared to nelfinavir. Conclusions: Here, we have demonstrated for the first time that ciprofloxacin and moxifloxacin may interact with COVID-19 Main Protease (M^pro).

A growing interest in the use of a combination of chemosensitizers and cytostatics for overcoming cancer resistance to treatment and the development of their delivery systems has been observed. Resveratrol (Res) presents antioxidant, anti-inflammatory and chemopreventive properties but also limits multidrug resistance against docetaxel (Dtx), which is one of the main causes of failure in cancer therapy with this drug. However, the use of both drugs presents challenges, including poor bioavailability, the unfavourable pharmacokinetics and chemical instability of Res and the poor water solubility and dose-limiting toxicity of Dtx. In order to overcome these difficulties, attempts have been made to create different forms of delivery for both agents. This review is focused on the latest developments in nanoparticles for the delivery of Dtx, Res and for the combined delivery of those two drugs. The aim of this review was also to summarize the synergistic mechanism of action of Dtx and Res on cancer cells. According to recent reports, Dtx and Res loaded in a nano-delivery system exhibit better efficiency in cancer treatment compared to free drugs. Also, the co-delivery of Dtx and Res in one actively targeted delivery system providing the simultaneous release of both drugs in cancer cells has a chance to fulfil the requirements of effective anticancer therapy and reduce limitations in therapy caused by multidrug resistance (MDR).

Although some fluoroquinolones have been found to exert anti-tumor activity, studies on the effect of these drugs on melanoma cells are relatively rare. The aim of this study was to examine the effect of lomefloxacin on cell viability, reactive oxygen species production, redox balance, cell cycle distribution, DNA fragmentation, and apoptosis in COLO829 melanoma cells. Lomefloxacin decreases the cell viability in a dose- and time-dependent manner. For COLO829 cells treated with the drug for 24, 48, and 72 h, the values of IC50 were found to be 0.51, 0.33, and 0.25 mmol/L, respectively. The analyzed drug also altered the redox signaling pathways, as shown by intracellular reactive oxygen species overproduction and endogeneous glutathione depletion. After lomefloxacin treatment, the cells were arrested in S- and G2/M-phase, suggesting a mechanism related to topoisomerase II inhibition. DNA fragmentation was observed when the cells were exposed to increasing lomefloxacin concentrations and a prolongation of incubation time. Moreover, it was demonstrated that the drug induced mitochondrial membrane breakdown as an early hallmark of apoptosis. The obtained results provide a strong molecular basis for the pharmacologic effect underlying the potential use of lomefloxacin as a valuable agent for the treatment of melanoma in vivo.