Calcium Carbonate Microspheres Loaded the Iron and Selenopeptide Conjugate with Human-Like Collagen Scaffold for Skin Filling and Gastric Cancer Therapy

The multifunctional scaffold/microsphere composite, utilizing protein or polypeptide as the scaffold or carrier, remains a significant medical challenge for skin tissue filling and cancer therapy. However, inadequate mechanical and bioadhesion properties hinder its clinical application. To overcome these challenges, multifunctional hydrogels have been developed with selenopeptide (ACBP-S-Se) and Fe preloaded into CaCO3 microspheres and cross-linked with human-like collagen (HLC) using transglutaminase to construct a CaCO3@Fe2+-ACBP-S-Se@HLC double-carrier hydrogel. The synthesis of this compound is based on the selenium (Se) element in ACBP-S-Se, which can acylate with the cysteines in the protein chain to form amide bonds. The three-dimensional structure of the double-carrier hydrogels, with adequate mechanical properties and implantable biodegradable and swelling ratio, is highly anticipated for excellent biocompatibility. The double-carrier hydrogel promotes L929 cell proliferation and adhesion and inhibits MKN-45 cell growth in vitro. Furthermore, the double-carrier hydrogel can form in situ and exhibit tissue biocompatibility after subcutaneous injection into mice. Compared with HLC hydrogels, the double-carrier hydrogel effectively increases the degradation rate in vivo. Additionally, the stable release of the hydrogel after injection into tumor-bearing nude mice enables it to reach the tumor site, promoting apoptosis of gastric cancer cells with enhanced deceleration of the cell cycle by blocking cell proliferation and growth. The modulation of relevant inhibitory genes in the tumor results in increased apoptosis in the tumor. In summary, the CaCO3@Fe2+-ACBP-S-Se@HLC double-carrier hydrogel leads to its cooperative induction of apoptosis and ferroptosis. This approach aims to develop a multifunctional and injectable supramolecular hydrogel for gastric cancer treatment.