Nanomedicines are applied as alternative treatments for anticancer agents. For the treatment of cancer, due to the small size in nanometers (nm), specific site targeting can be achieved with the use of nanomedicines, increasing their bioavailability and conferring fewer toxic side effects. Additionally, the use of minute amounts of drugs can lead to cost savings. In addition, nanotechnology is effectively applied in the preparation of such drugs as they are in nm sizes, considered one of the earliest cutoff values for the production of products utilized in nanotechnology. Early concepts described gold nanoshells as one of the successful therapies for cancer and associated diseases where the benefits of nanomedicine include effective active or passive targeting. Common medicines are degraded at a higher rate, whereas the degradation of macromolecules is time-consuming. All of the discussed properties are responsible for executing the physiological behaviors occurring at the following scale, depending on the geometry. Finally, large nanomaterials based on organic, lipid, inorganic, protein, and synthetic polymers have also been utilized to develop novel cancer cures.

Development and formulation of an efficient and safe therapeutic regimen for cancer theranostics are dynamically challenging. The use of mono-therapeutic cancer regimen is generally restricted to optimal clinical applications, on account of drug resistance and cancer heterogeneity. Combinatorial treatments can employ multi-therapeutics for synergistic anticancer efficacy whilst reducing the potency of individual moieties and diminishing the incidence of associated adverse effects. The combo-delivery of nanotherapeutics can optimize anti-tumor efficacy while reversing the incidence of drug resistance, aiming to homogenize pharmacological profile of drugs, enhance circulatory time, permit targeted drug accumulation, achieve multi-target dynamic approach, optimize target-specific drug binding and ensure sustained drug release at the target site. Numerous nanomedicines/nanotherapeutics have been developed by having dynamic physicochemical, pharmaceutical and pharmacological implications. These innovative delivery approaches have displayed specialized treatment effects, alone or in combination with conventional anticancer approaches (photodynamic therapy, radiotherapy and gene therapy), while reversing drug resistance and potential off-target effects. The current review presents a comprehensive overview of nanocarrier aided multi-drug therapies alongside recent advancements, future prospects, and the pivotal requirements for interdisciplinary research.

BackgroundThe present study investigates the hepato- and DNA-protective effects of standardized extracts of Cleome brachycarpa (cabralealactone), Solanum incanum (solasodin), and Salvadora oleioides (salvadorin) in rats.Materials and methodsHepatotoxicity was induced with intraperitoneal injection of carbon tetrachloride (CCl4) (1 mL/kg b.wt.) once a week for 12 weeks. The hepato- and DNA protective effects of the extracts in different combinations were compared with that of a standard drug Clavazin (200 mg/kg b.wt.). Tissue alanine aminotransferase, alpha-fetoprotein, tumor necrosis factor alpha (TNF-α), isoprostanes-2α, malondialdehyde, and 8-hydroxydeoxyguanosine, the significant hallmarks of oxidative stress, were studied.ResultsHistopathological findings of the liver sections from the rat group which received CCl4+cabralealactone, solasodin, and salvadorin demonstrated improved centrilobular hepatocyte regeneration with moderate areas of congestion and infiltration comparable with Clavazin. For in silico study, the identified compounds were subjected to molecular docking with cyclooxygenase-2 and TNF-α followed by a molecular dynamics study, which indicated their potential as anti-inflammatory agents.ConclusionCabralealactone, solasodin, and salvadorin confer some hepatoprotective and DNA-damage protective effects against CCl4-induced toxicity. They successfully restored the normal architecture of hepatocytes and have the potential to be used as inhibitor to main culprits, that is, cyclooxygenase-2 and TNF-α. They can combat oxidative stress and liver injuries both as mono and combinational therapies. However, combination therapy has more ameliorating effects.

BackgroundCancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders.Materials and methodsThe concentration of oxidative stress markers such as MDA, NO and levels of different antioxidant molecules such as SOD, CAT, GSH, GPx, GPr, VIT A, VIT E and VIT C present in the serum of chemotherapy treated patients (n = 50) and in normal persons (n = 20) were estimated by the direct spectrophotometric method while the concentration of TNF-α and MMP-9 activity were determined using human TNF-α and MMP-9 ELISA kits.ResultsThe concentration of SOD and CAT (0.356 ± 0.05 μg/dl and 1.26 ± 0.01 μmol/mol of protein) was significantly lower as compared to that (1.09 ± 0.03 μg/dl and 3.99 ± 0.04 μmol/mol of protein) in controls. The levels of GPx (0.06 ± 0.01 mmol/dl) in the cancer patients were much lower than those in the controls (0.78 ± 0.06 mmol/dl). Lower level of GSH (0.96 ± 0.003 μg/dl) in serum of the diseased group was observed as compared to healthy group (7.26 ± 1.40 μg/dl). The level of Vit A, Vit C and Vit E was lower in systemic circulation of cancer patients (109.99 ± 6.35 μg/ml, 1.26 ± 0.36 μg/ml and 1.29 ± 0.191 μg/ml) as compared to control subjects (166.35 ± 14.26 μg/ml, 3.25 ± 0.099 μg/ml and 6.354 ± 2.26 μg/ml) respectively. The concentration of nitric oxide was significantly higher in the cancer patients (45.26 ± 6.35 ng/ml) than that in the normal subjects (16.35 ± 3.26 ng/ml). The higher concentration of MDA (8.65 ± 3.26 nmol/ml) was observed in the patients than normal ones (1.254 ± 0.065 nmol/ml). The quantity of TNF-α was significantly higher in chemotherapy treated patients (32.68 ± 4.33 pg/ml) as compared to the control group (20.979 ± 1.98 pg/ml). Significantly higher concentration of MMP-9 (40.26 ± 3.26 ng/ml) was observed in the cancer patients than the controls (7.256 ± 1.95 ng/ml).ConclusionLower levels of antioxidant enzymes and non-enzymatic small molecules and higher levels of oxidative stress and inflammatory clinical parameters such as NO, MDA, TNF-α and MMP-9 may be involved in the pathogenesis of systemic chemotherapy related ocular complications such as cataract, glaucoma, blepharitis, retinitis pigmentosa, macular degeneration, pterygium and retinal degeneration.

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.