Folate receptor-mediated delivery system based on chitosan coated polymeric nanoparticles for combination therapy of breast cancer.

Combination therapy using two or more drugs with different mechanisms of action is an effective strategy for treating cancer. This is because of the synergistic effect of complementary drugs that enhances their effectiveness. However, this approach has some limitations, such as non-specific distribution of the drugs in the tumor and the occurrence of dose-dependent toxicity to healthy tissues. To overcome these issues, we have developed a folate receptor-mediated co-delivery system that improves the access of chemotherapy drugs to the tumor site. We prepared a nanoplatform by encapsulating paclitaxel (PTX) and curcumin (CUR) in poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) co-polymer using a double emulsion method and coating nanoparticles with pH-responsive chitosan-folic acid (CS-FA) conjugate. The nanocarrier's physicochemical properties were studied, confirming successful preparation with appropriate size and morphology. PTX and CUR could be released synchronously in a controlled and acid-facilitated manner. The dual drug-loaded nanocarrier exhibited excellent anti-tumor efficiency in MDA-MB-231 cells in vitro. The active targeting effect of FA concluded from the high inhibitory effect of dual drug-loaded nanocarrier on MDA-MB-231 cells, which have overexpressed folate receptors on their surface, compared to Human umbilical vein endothelial cells (HUVEC). Overall, the nanoengineered folate receptor-mediated co-delivery system provides great potential for safe and effective cancer therapy.

Differential gene-expression of metallothionein 1M and 1G in response to zinc in sertoli TM4 cells.

BACKGROUND: Zinc (Zn) as an important trace element is essential for testicular development and spermatogenesis. Molecular mechanism of Zn action in the reproductive system may be related to metal binding low-molecular weight proteins, metallothioneins (MT). Our objective was to determine the effect of Zn on two important isoforms of MT, MT1M and MT1G genes expression on testicular sertoli cells. METHODS: Cultured sertoli TM4 cells were exposed to different concentrations of Zn at different time points. Cellular uptake of Zn was tested using flame atomic absorption spectrometry. The cellular viability and gene expression were assessed by MTT and real-time PCR methods, respectively. RESULTS: The treated cells resulted in higher Zn concentration and cellular viability. The expression of MT1M and MT1G genes in the treated cells were greater than those of the untreated cells (P less than 0.05). In the high dosage treated group (100 and 500 muM), Zn concentration and expression of MT1M and MT1G genes increased three h after treatment; MT1G gene expression increased more at sixth h. At 18th h of treatment, the expression of both genes especially MT1G, increased dramatically while Zn concentration decreased. CONCLUSION: Since the increase of MT1G mRNA was coincident with cellular Zn level, it seems that MT1G has a more prominent role than MT1M in the homeostasis of Zn. In addition, Zn at dosage of 50 muM (pharmacologic concentration) may protect cells by increasing the expression of MT genes at longer periods.

Effect of contraceptive pill on the selenium and zinc status of healthy subjects.

BACKGROUND: The study was conducted to ascertain the influence of oral contraceptive pill (OCP) uptake on serum zinc and selenium in contraceptive pill users. STUDY DESIGN: The concentration of zinc and selenium was determined by atomic absorption spectrophotometer in 50 healthy women with normal menstrual cycles as a control group and 50 women taking low-dose OCP. RESULTS: The control reference values were 81.61+/-9.44 and 70.35+/-25.57 mcg/dL, which were obtained for zinc and selenium, respectively. Use of OCP resulted in a significant decrease in serum zinc levels (p