Dual drug release mechanisms through mesoporous silica nanoparticle/electrospun nanofiber for enhanced anticancer efficiency of curcumin.

Electrospun nanofibers (NFs)-based drug delivery approaches are of particular interest as a hopeful implantable nanoplatform for localized cancer therapy and treating tissue defect after resection, allowing the on-site drug delivery with minimal side effect to healthy cells. To maintain therapeutic concentrations of anticancer molecules for a relatively long time through a combination of burst and sustained drug release mechanisms, a hybrid of polycaprolactone and gelatin (PCL/GEL) was used for co-encapsulation of free curcumin (CUR) and CUR-loaded mesoporous silica nanoparticles (CUR@MSNs) via electrospinning, resulting in a novel drug-loaded nanofibrous scaffold, CUR/CUR@MSNs-NFs. The as-prepared MSNs and composite NFs were characterized via TGA, FTIR, FE-SEM, TEM, and BET. In vitro release profile of CUR from CUR/CUR@MSNs-NFs was examined, and the in vitro antitumor efficacy against MDA-MB-231 breast cancer cells was also evaluated through MTT, scratch assay, DAPI staining, and real-time PCR. The results disclosed that the smooth, bead-free, and randomly oriented CUR/CUR@MSNs-NFs displayed a combination of initial rapid discharge and sustained release for CUR, which led to higher cytotoxicity, lower migration as well as a more pronounced effect on apoptosis induction than CUR-NFs and CUR@MSNs-NFs. The present study illustrated that the dual drug release mechanisms through MSN/NF-mediated drug delivery systems might have a highly hopeful application as a localized implantable scaffold for potential postoperative breast cancer therapy.

In vitro expansion of human adipose-derived stem cells with delayed senescence through dual stage release of curcumin from mesoporous silica nanoparticles/electrospun nanofibers.

Electrospun nanofibers (NFs) were utilized to realize the dual-stage release of curcumin (Curc) to fully support the attachment, viability and proliferation of adipose-derived stem cells (hADSCs) with a delay in cellular senescence. For this purpose, both free Curc and Curc-loaded mesoporous silica nanoparticles (Curc@MSNs) were integrated into the electrospun polycaprolactone/gelatin (PCL/GEL) nanofibrous scaffolds and characterized via FTIR, BET, FE-SEM and TEM. In vitro drug release results demonstrated strong dual stage-discharge of Curc from the Curc/Curc@MSNs-NFs. Because of the combination of initial rapid release and late extended drug release, hADSCs cultured on the Curc/Curc@MSNs-NFs showed the greatest adhesion, metabolic activity and proliferation rate with a fibroblastic phenotype after 28 days of culture. Besides, a significant reduction in senescence-associated lysosomal α-L-fucosidase (SA-α-Fuc) expression and activity was also measured in hADSCs cultured on the Curc/Curc@MSNs-NFs. Moreover, not only the expression of hTERT in mRNA and protein levels was considerably increased in hADSCs seeded on the Curc/Curc@MSNs-NFs, but also the telomerase activity and telomere length were significantly enhanced in the scaffolds compared to the other types of scaffolds and control group. These results uncovered the potential of the two-stage discharge profile of Curc from Curc/Curc@MSNs-NFs to provide the biofunctionality of long-term cultured hADSCs for efficient stem cell-based regenerative therapies.

Prolonged proliferation and delayed senescence of the adipose-derived stem cells grown on the electrospun composite nanofiber co-encapsulated with TiO2 nanoparticles and metformin-loaded mesoporous silica nanoparticles.

This study was aimed to investigate the effects of the Poly-ε-Caprolactone/Gelatin nanofibers (PCL/GEL NFs) co-encapsulated with TiO2 nanoparticles (nTiO2) and metformin-loaded mesoporous silica nanoparticles (MET@MSNs) on prolonging the in vitro expansion of human adipose-derived stem cells (hADSCs) without inducing cellular senescence and aging. FTIR, BET, FE-SEM, and TEM were applied to characterize the fabricated MET@MSNs and electrospun composite NFs. The presence of inorganic particles, nTiO2 and MSNs, in the scaffolds improved their mechanical properties and led to a more sustained release of MET with almost the lack of the initial burst release from nTiO2/MET@MSNs-loaded NFs. The enhanced adhesion, metabolic activity, and proliferation rate of the hADSCs grown on nTiO2/MET@MSNs-loaded NFs were demonstrated via FE-SEM images, MTT test and PicoGreen assay, respectively, over 28 days of culture. Furthermore, the irregular nanofibrillar structures and the impact of sustained release of MET led to a significant upregulation in the mRNA levels of autophagy (Atg-5, Atg-7, Atg-12, and Beclin-1) and stemness (Nanog3, Sox-2, and Oct-4) markers as well as a considerable down-regulation of p16INK4A senescence marker. Further, the upregulation of hTERT, enhanced activity of telomerase, and increased telomere length were more pronounced in the hADSCs cultured on nTiO2/MET@MSNs-loaded NFs as compared to other types of NFs. Overall, our findings demonstrated the potential of the fabricated nanocomposite platform for counteracting cellular senescence and achieving sufficient quantities of fresh hADSCs with preserved stemness for various stem cell-based regenerative medicine purposes.