Angiogenesis and re-epithelialization are critical factors in skin wound healing. Growth factors and stem cells have demonstrated their active roles in promoting these two processes. Peptides show the similar effects with growth factors with lower cost and controllable property. Here we report a biomimetic fragment of the laminin -Ser-Ile-Lys-Val-Ala-Val (SIKVAV), conjugated chitosan hydrogel that can promote the skin regeneration. In vitro we found that this peptide conjugated hydrogel significantly promoted BMSCs adhesion and proliferation. In vivo, this hydrogel accelerated the wound contraction. The subcutaneous implantation test and H&E staining results revealed that peptide modified chitosan hydrogel dramatically led to the formation of new blood vessels. Moreover, Masson staining discovered that many newborn collagen fibers appeared in peptide hydrogel group, while only a few newborn collagen fibers were found in control and chitosan hydrogel group. The peptide chitosan hydrogel also reepithelialized quickly, while the control and chitosan hydrogel took more time to complete.These results suggest that the SIKVAV peptide is an effective motif to significantly improve chitosan's function in angiogenesis and re-epithelialization of skin.anhydride to obtain double bonds conjugated chitosan (D-chitosan) with 29% conjugation rate (Fig. S1). SMP then acted as a crosslinker by reacting N-hydroxysuccinimide of SMP with amine groups of chitosan, then the N-succinimidyl group reacted with the thiol group of cysteine in peptide. The 1 H-NMR results showed the peptide was successfully conjugated to D-chitosan ( Fig.2B). Fig.2 The synthesis and characterization of peptide-chitosan. (A) The synthesis route of peptide conjugated Dchitosan; (B) 1 H-NMR characterization of peptide conjugated D-chitosan.
This study developed a kind of magnetic-polymer nanocarrier with folate receptor-targeting and pH-sensitive multifunctionalities to carry doxorubicin (DOX) for treatment of advanced gastric cancer (AGC). Folate-conjugated, pH-sensitive, amphiphilic poly(β-aminoester) self-assembled with hydrophobic oleic acid-modified iron oxide nanoparticles, and the resulting hydrophobic interaction area is a reservoir for lipophilic DOX (F-P-DOX). Confocal microscopy illustrated that F-P-DOX treatment could keep higher DOX accumulation in cells than P-DOX (without folate conjugation), and therefore get a higher efficiency of DOX internalization at pH 6.5 than at pH 7.4. Electron microscope characterization and real-time polymerase chain reaction revealed cell apoptosis promoted by F-P-DOX. The better efficacy of F-P-DOX on GC than free DOX and P-DOX was determined by MTT assay and xenograft model. Moreover, the accumulation of F-P-DOX in the tumor site was detected by magnetic resonance imaging (MRI). All those observations suggest F-P-DOX could be a promising theranostic candidate for AGC treatment.
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