•Overview of the transition metal complexes as photosensitizers.•Integration of metal complexes with biomolecules for targeted antitumor application.•The future perspectives for metal-based PSs are ...outlined.
Light, oxygen and photosensitizers (PSs) are the three separate elements that have been applied in combination in the phototherapy of cancers in the past decades. Currently, platinum (Pt)-based drugs still account for approximately 50% of traditional chemotherapies used in the clinic. Transition metal complexes with unique and versatile photochemical and photophysical properties have appeared as promising systems for both photodynamic therapy and photoactivated chemotherapy. The highly potent photobiological activity based on energy transfer and electron transfer processes takes advantage of these properties. In this perspective article, we discuss the development of transition metal complexes (TMCs) with meaningful designs for the diagnosis and therapy of malignant tumors, including octahedral Ru(II) (ruthenium), Pt(IV) and Rh(III) (rhodium) PSs and in the early stages of Ir(III) (iridium) and Os(II) (osmium) complexes. The combination of organometallics with other active targeting moieties, such as antibodies, peptides, and aptamers, resulting in increased selectivity and reduced side-effects, will then be discussed. The challenges and future perspectives in this field will also be discussed. This review not only provides useful information for the future design of chemically innovative TMC-based anticancer drug candidates with clear mechanisms of action and drug targets, but also sheds light into the discovery of metal-based PSs to improve cancer treatment.
Organo-seleno compounds (org-Se) have been widely used in antitumor, antiviral, and antiinflammatory therapy; antioxidation and other biological fields. As such, they have made an important ...contribution to overcoming various kinds of diseases, and researchers are increasingly attracted to org-Se's synthesis and functional design. This review is mainly focused on the design and synthesis of various kinds of org-Se, followed by their anticancer mechanisms such as the mitochondria mediated pathway induced by ROS, death receptor mediated pathways involving p53 phosphorylation, and the activation of the AMPK pathway to promote apoptosis. Org-Se also serves as a sensitizer in chemotherapy and radiotherapy, and an antagonist against the cytotoxic effects induced by chemotherapeutic agents. Finally, we will summarize the development of cancer-targeted org-Se containing complexes, and nanotechnology-based org-Se for anticancer application. This review could provide information for the future design of chemically innovative org-Se with anticancer potential, and shed light on the discovery of nanomaterial-based pharmaceuticals to improve drug development and formation.
The blood–brain barrier (BBB) is the main bottleneck to prevent some macromolecular substance entering the cerebral circulation, resulting the failure of chemotherapy in the treatment of glioma. ...Cancer nanotechnology displays potent applications in glioma therapy owing to their penetration across BBB and accumulation into the tumor core. In this study, we have tailored the particle size of mesoporous silica nanoparticles (MSNs) through controlling the hydrolysis rate and polycondensation degree of reactants, and optimized the nanosystem that could effectively penetrate BBB and target the tumor tissue to achieve enhanced antiglioma efficacy. The nanoparticle was conjugated with cRGD peptide to enhance its cancer targeting effect, and then used to load antineoplastic doxorubicin. Therefore, the functionalized nanosystem (DOX@MSNs) selectively recognizes and binds to the U87 cells with higher expression level of ανβ3 integrin, sequentially enhancing the cellular uptake and inhibition to giloma cells, especially the particle size at 40 nm. This particle could rapidly enter cancer cells and was difficult to excrete outside the cells, thus leading to high drug accumulation. Furthermore, DOX@MSNs exhibited much higher selectivity and anticancer activity than free DOX and induced the glioma cells apoptosis through triggering ROS overproduction. Interestingly, DOX@MSNs at about 40 nm exhibited stronger permeability across the BBB, and could disrupt the VM-capability of glioma cells by regulating the expression of E-cadherin, FAK, and MMP-2, thus achieving satisfactory antiglioblastoma efficacy and avoiding the unwanted toxic side effects to normal brain tissue. Taken together, these results suggest that tailoring the particle size of MSNs nanosystem could be an effective strategy to antagonize glioblastoma and overcome BBB.
Coordination-driven surface modification is an effective strategy to achieve nanosystem functionalization and improved physicochemical performance. Black phosphorus (BP)-based nanomaterials ...demonstrate great potential in cancer therapy, but their poor stability, low X-ray mass attenuation coefficient, and nonselectivity limit the application in radiotherapy. Herein, we used unsaturated iridium complex to coordinate with BP nanosheets to synthesize a two-dimensional layered nanosystem (RGD-Ir@BP) with higher biostability. Ir complex improves the photoelectric properties and photoinduced charge carrier dynamics of BP, hence Ir@BP generated more singlet oxygen after X-ray irradiation. In in vivo experiments, with X-ray irradiation, RGD-Ir@BP effectively inhibited nasopharyngeal carcinoma tumor growth but with minor side effects. Additionally, based on untargeted metabolomics analysis, the combined treatment specifically down-regulated the tumor proliferative mark of prostaglandin E2 in cancer cells. In general, this study provides a design strategy of high-performance coordination-driven BP-based nanosensitizer in cancer radiotherapy.
Surface charge plays a key role in cellular uptake and biological actions of nanomaterials. Selenium nanoparticles (SeNPs) are novel Se species with potent anticancer activity and low toxicity. This ...study constructed positively charged SeNPs by chitosan surface decoration to achieve selective cellular uptake and enhanced anticancer efficacy. The results of structure characterization revealed that hydroxyl groups in chitosan reacted with SeO3 2– ion to form special chain-shaped intermediates, which could be decomposed to form crystals upon reduction by ascorbic acid. The initial colloids nucleated and then assembled into spherical SeNPs. The positive charge of the NH3 + group on the outer surface of the nanoparticles contributed to the high stability in aqueous solutions. Moreover, a panel of four human cancer cell lines were found to be susceptible to SeNPs, with IC50 values ranging from 22.7 to 49.3 μM. Chitosan surface decoration of SeNPs significantly enhanced the selective uptake by endocytosis in cancer cells and thus amplified the anticancer efficacy. Treatment of the A375 melanoma cells with chitosan–SeNPs led to dose-dependent apoptosis, as evidenced by DNA fragmentation and phosphatidylserine translocation. Our results suggest that the use of positively charged chitosan as a surface decorator could be a simple and attractive approach to achieve selective uptake and anticancer action of nanomaterials in cancer cells.
The impact of sarcopenia on the outcome of gastrointestinal (GI) oncological patients is still controversial. We aim to discuss the prevalence of sarcopenia and its relation to the oncological ...outcome.
Embase, Medline, PubMed, and the Cochrane library were systematically searched for related keywords. Studies using CT to assess sarcopenia and evaluate its relationship with the outcome of GI oncological patients were included. Long-term outcomes, including overall survival and disease-free survival, were compared by hazard ratios (HRs) with 95% confidence intervals (CIs). Short-term outcomes, including total complications and major complications (Clavien-Dindo ≥IIIa) after curable surgery, were compared by the risk ratio (RR) and 95% CI.
A total of 70 studies including 21,875 patients were included in our study. The median incidence of sarcopenia was 34.7% (range from 2.1 to 83.3%). A total of 88.4% of studies used skeletal muscle index (SMI) in the third lumbar level on CT to define sarcopenia, and a total of 19 cut-offs were used to define sarcopenia. An increasing trend was found in the prevalence of sarcopenia when the cut-off of SMI increased (β = 0.22, 95% CI = 0.12-0.33, p < 0.001). The preoperative incidence of sarcopenia was associated both with an increased risk of overall mortality (HR = 1.602, 95% CI = 1.369-1.873, P < 0.001) and with disease-free mortality (HR = 1.461, 95% CI = 1.297-1.646, P < 0.001). Moreover, preoperative sarcopenia was a risk factor for both total complications (RR = 1.188, 95% CI = 1.083-1.303, P < 0.001) and major complications (RR = 1.228, 95% CI = 1.042-1.448, P = 0.014).
The prevalence of sarcopenia depends mostly on the diagnostic cut-off points of different criteria. Preoperative sarcopenia is a risk factor for both long-term and short-term outcomes.
5-HMF is widely presented in foods and produced through the degradation of hexoses and Maillard reaction during heat treatment of foods containing reducing sugars and amino acids in an acid ...environment. However, controversial conclusions on the biological effects of 5-HMF have been drawn in previous studies. Therefore, the main aim of this study was to investigate the antioxidant and antiproliferative activities of 5-HMF. The 2,2′-azinobis-3-ethylbenzothiazolin-6-sulfonic acid (ABTS) assay, the 1,1-diphenyl-2-picryhydrazyl (DPPH) assay, and the hemolysis assay induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) were performed to evaluate the antioxidant capacity of 5-HMF. The results showed that 5-HMF exhibited novel antioxidant activity by scavenging the ABTS and DPPH free radicals and inhibited the AAPH-induced hemolysis in a dose-dependent manner. In the hemolysis assay, the reduction of ROS and MDA contents and the increase in enzyme activities of SOD, CAT, and GPx were found in erythrocytes pretreated with 5-HMF, which demonstrated that 5-HMF could prevent the peroxidation from the source to protect the erythrocytes. The morphological changes of erythrocytes was also verified by observation using atomic force microscopy. The inhibitory effect of 5-HMF on human cancer cell proliferation was investigated by MTT assay, flow cytometric analysis, and the TUNEL and DAPI costaining assay. The results showed that 5-HMF displayed higher antiproliferative activity on human melanoma A375 cells than other cell lines. Further investigation on the action mechanisms revealed that 5-HMF could induce A375 cell apoptosis and G0/G1 cell cycle arrest. The A375 cell apoptosis that 5-HMF induced was characterized by a TUNEL and DAPI costaining assay. These findings suggest that 5-HMF could be developed as a novel natural antioxidant with potential applications in cancer chemoprevention.
The incidence and mortality rates of lung cancer are among the highest in the world. Traditional treatment methods include surgery, chemotherapy, and radiotherapy. Although rapid progress has been ...achieved in the past decade, treatment limitations remain. It is therefore imperative to identify safer and more effective therapeutic methods, and research is currently being conducted to identify more efficient and less harmful drugs. In recent years, the discovery of antitumor drugs based on the essential trace element selenium (Se) has provided good prospects for lung cancer treatments. In particular, compared to inorganic Se (Inorg-Se) and organic Se (Org-Se), Se nanomedicine (Se nanoparticles; SeNPs) shows much higher bioavailability and antioxidant activity and lower toxicity. SeNPs can also be used as a drug delivery carrier to better regulate protein and DNA biosynthesis and protein kinase C activity, thus playing a role in inhibiting cancer cell proliferation. SeNPs can also effectively activate antigen-presenting cells to stimulate cell immunity, exert regulatory effects on innate and regulatory immunity, and enhance lung cancer immunotherapy. This review summarizes the application of Se-based species and materials in lung cancer diagnosis, including fluorescence, MR, CT, photoacoustic imaging and other diagnostic methods, as well as treatments, including direct killing, radiosensitization, chemotherapeutic sensitization, photothermodynamics, and enhanced immunotherapy. In addition, the application prospects and challenges of Se-based drugs in lung cancer are examined, as well as their forecasted future clinical applications and sustainable development.
Mesoporous silica nanoparticles (MSNs) have been well‐demonstrated as excellent carriers for anticancer drug delivery. Presented here is a cancer‐targeted MSNs drug delivery system that allows the ...direct fluorescence monitoring of the cellular uptake and localization of theranostic agents in cancer cells. Specifically, the anticancer action mechanisms of RGD peptide‐functionalized MSNs carrying ruthenium polypyridyl complexes (RuPOP@MSNs) are elucidated in detail. RGD peptide surface decoration significantly enhances the cellular uptake of the nanoparticles through receptor‐mediated endocytosis, and increases the selectivity between cancer and normal cells. RuPOP@MSNs exhibits unprecedented enhanced cytotoxicity toward cancer cells overexpressing integrin receptor, which is significantly higher than that of free RuPOP, through induction of apoptosis. The important contribution of extrinsic pathway to cell apoptosis is confirmed by increase in expression levels of death receptors, activation of caspase‐8 and truncation of Bid. The internalized nanoparticles release free RuPOP into the cytoplasm, where they modulate the phosphorylation of p53, AKT, and MAPKs pathways to promote cell apoptosis. Moreover, the strong autofluorescence of RuPOP permits the direct monitoring of drug delivery, and extends the power of theranostics to subcellular level. Taken together, this study provides an effective strategy for the design and development of cancer‐targeted theranostic agents.
Cancer‐targeted MSNs loaded with a novel Ru polypyridyl complex (RuPOP@MSNs) that allows the direct fluorescence monitoring of the cellular uptake and localization of anticancer agents in cancer cells are presented. The internalized RuPOP@MSNs can control the release of free Ru complex to trigger ROS‐mediated p53 phosphorylation and to regulate the AKT and MAPKs signaling pathways.
Selenocystine (SeC) is a nutritionally available selenoamino acid with selective anticancer effects on a number of human cancer cell lines. The present study shows that SeC inhibited the ...proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt. Inhibitors of ERK (U0126) and Akt (LY294002), but not JNK (SP600125) and p38 MAPK (SB203580), suppressed SeC-induced S-phase arrest and apoptosis in MCF-7 cells. The findings establish a mechanistic link between the PI3K/Akt pathway, MAPK pathway, and SeC-induced cell cycle arrest and apoptosis in MCF-7 cells.
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