Nan Wang,Shuying Zhao,Xiaoyong Tian,Shanyi Guang,Hongyao Xu
Traditional dressings, such as bandages, gauze, and cotton pads stick to new granulation tissue, thereby aggravating wound injury or causing secondary injury during replacement. Microspheres that are biodegradable and adaptable to various wound shapes are a good alternative to traditional dressings. In this work, a novel microsphere was prepared by reverse microemulsion method using sodium alginate and silk peptide (SP) as the aqueous phase. After cross-linking by Ca 2+ , calcium alginate (CA) and SP composite microspheres called CA/SP were prepared. By adjusting the SP content, the swelling rate of microspheres reached 1050 % and the pore diameter reached 19.59 nm. In addition, the introducing SP provided a stable loading site for thrombin (Th). This platform (called CA/SP@Th)—integrating rapid blood enrichment, calcium release , and Th catalysis—can ensure rapid hemostasis in a variety of bleeding models. Additionally, the SP present in this modality also promoted fibroblast proliferation, this increased the wound closure rate in a total cortex injury mouse model (more than 97 % within 15 days). Therefore, CA/SP@Th can be used as a multifunctional dressing for rapid hemostasis and wound healing.
Non-steroidal anti-inflammatory drugs (NSAIDs) have drawn considerable attention in the field of cancer treatment, yet these drugs display limited potency and selectivity against cancer cells. To address these problems, we designed a peptide-based self-delivery system [Indomethacin-Phe-Phe-Tyr (H2PO3)-Ser-Val, IDM-FFpYSV] that combines an NSAID molecule (indomethacin, or IDM) and a segment of anticancer tripeptide (tyroservatide, or YSV). IDM-FFpYSV is capable of self-assembling in an aqueous solution to afford nanofibrillar hydrogels under the catalysis of alkaline phosphatases (ALPs), which are overexpressed on the plasma membrane of cancer cells. The IDM-FFpYSV + ALP hydrogel displays a continuous release profile of peptide drugs, whereas a solution mixture of pure drugs (IDM-OH + pYSV + ALP) shows burst release of drug moieties. The treatment of IDM-FFpYSV selectively inhibits the proliferation of HeLa cells in vitro, with precise regulations of intracellular targeting proteins (COX-2 and AC-H3). The enhanced potency and selectivity of IDM-FFpYSV are found to be attributed to enhanced cellular uptake of peptide drugs, which involves a caveolae-mediated endocytosis pathway. Furthermore, intravenous administration of the IDM-FFpYSV formulation significantly inhibits the tumor growth in a HeLa-xenografted mouse model, whereas treatment of solution mixtures of pure drugs (IDM-OH + pYSV) fails to do so. Taken together, the study provides a viable strategy to augment anticancer efficacies of self-delivery system through molecular integration of multiple anticancer elements with an enzyme-instructed self-assembly process.
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