ABSTRACT
Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel (DTX) in NP, delivered MSC accumulated in the lung. Both MSC/A549 cell experiments and MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.
ABSTRACT
Objective To compare the impacts of subtotal nephrectomy and ischemiareperfusion injury on renal stem cells and progenitor cells of rats,and to explore the significance of renal stem cells and progenitor cells for renal repair and the possible mechanisms of prognosis in rats with acute renal failure (ARF) or chronic renal failure (CRF).Methods Rats of CRF or ARF model underwent 5/6 nephrectomy or renal artery ligation and repedusion respectively,and rars in control group underwent sham operation.Scr,BUN and 24 hour urine protein were regularly measured.Kidney specimens were obtained at the set time for HE staining and fluorescence staining.Expressions of CD24,CD133 and podocin were detected by immunofluorescence.RT-PCR was performed to quantify the expression of transforming growth factor β1 (TGF-β1),Notch2,hepatocyte growth factor (HGF),bone morphogenetic protein 7 (BMP7) and Pax-2 mRNA in renal tissue and the expression of podocin mRNA in renal cortex.Correlation among the expressions of Pax-2 mRNA,podocin mRNA and glomemlosclerosis index were analyzed.Results The rats of two models presented typical ARF or CRF in renal pathology and function.Glomerulosclerosis index in CRF group increased gradually with time,which were (2.34±0.28)％,(25.12±5.67)％,(89.42±12.28)％ and (171.23±32.28)％ at day 14,day 30,day 60 and day 90 respectively.Compared with sham group,the CD24+CD133+ cells of the ARF rats showed no significant change in quantity and distribution,while the CRF rats showed gradual reduction of CD24 +CD133+ cells.The expression of podocin in glomerulus decreased temporarily and recovered finally after ischemiareperfusion injury,but decreased gradually after 5/6 nephrectomy.Compared with sham group,expression of TGF-β1,Notch2 mRNA in renal tissue was increased in CRF group,while the expression of HGF,BMP7 mRNA in renal tissue of ARF group were increased.Between the expression of Pax-2 mRNA in renal tissue and the expression of podocin mRNA in renal cortex,there was positive correlation in CRF group,while they both were negatively correlated with glomerulosclerosis index.Conclusions Ischemia-reperfusion injury makes no obvious impairment to renal progenitor cells.Having progressively injured the living environment of renal progenitor cells,subtotal nephrectomy reduces renal progenitor cells,and causes podocytes to repairing incompetently,which may be the main pathogenesis of CRF with poor prognosis.