cRGD-based MRI imaging-enhanced nanoplatform helps DOX target pancreatic cancer.

Abstract

This project aims to construct cRGD functionalized mesoporous silica nanoparticles and cRGD modified mesoporous silica nanoparticles for the diagnosis and treatment of tumors, providing new ideas for targeted therapy of tumors. The mesoporous silica nanoparticles were doped with gadolinium in situ to provide excellent imaging; cRGD was coupled on the particle surface to confer particle targeting; and hyaluronic acid was loaded onto the particles by electrostatic adsorption, thereby improving the biocompatibility of the particles and prolonging their in vivo circulation time.Taking pancreatic cancer as a model, we studied its targeting ability to pancreatic cancer and its phagocytosis to cancer cells; Using methods such as cell growth experiments and flow cytometry, the anti-cancer effect and pro apoptotic effect of the system were studied. In vivo distribution, tumor targeting and therapeutic efficacy of nanoparticles evaluated in a mouse model of pancreatic cancer with loaded tumors.Evaluate the bioavailability and enrichment of nanoparticles in tumor tissue using MRI technology. Evaluate the therapeutic effect and safety through changes in tumor volume, histopathological examination, and prognosis. Characterization of the synthesis results proved that cRGD-HA-DOX-Gd₂O₃@MSN (cHDG@MSN) was successfully synthesized with a particle size of 230.83 ± 12.36 nm.In vitro drug release experiments of DOX were carried out at different pH values (5.5 and 7.4), where the release was only up to 22.65% at pH 7.4, whereas DOX release was increased up to 78.75% at pH = 5.5.The results confirm the pH responsiveness of this nanocarrier platform.The results of cytotoxicity studies showed that cHDG@MSN itself is not cytotoxic. Biosafety evaluation and hemolysis test results confirmed that the probe is highly biocompatible.Notably, Gd³⁺ significantly enhanced the T₁ contrast of the system according to MR imaging results.The apoptosis rates of SW1990 cells treated with PBS, DOX and cHDG@MSN in flow cytometry were 13.97%, 18.38% and 29.02%, respectively, demonstrating the effectiveness of the nanoprobes at the cellular level. Animal experiments demonstrated the effectiveness of nanoprobes at the pathological level and imaging level.Cells and animals demonstrated that cHDG@MSN effectively inhibited the proliferation of pancreatic cancer cells. This research further verified the pH sensitivity of the constructed compound drug delivery system to achieve accurate diagnosis and treatment of pancreatic cancer tumor cells.