cRGD-Conjugated GdIO Nanoclusters for the Theranostics of Pancreatic Cancer through the Combination of T1–T2 Dual-Modal MRI and DTX Delivery

Abstract

Clinically, magnetic resonance imaging (MRI) often uses contrast agents (CAs) to improve image contrast, but single-signal MRI CAs are often susceptible to calcification, hemorrhage, and magnetic sensitivity. Herein, iron acetylacetone and gadolinium acetylacetone were used as raw materials to synthesize a T1–T2 dual-mode imaging gadolinium-doped iron oxide (GdIO) nanocluster. Moreover, to endow the nanoclusters with targeting properties and achieve antitumor effects, the cyclic Arg-Gly-Asp (cRGD) peptide and docetaxel (DTX) were attached to the nanocluster surface, and the efficacy of the decorated nanoclusters against pancreatic cancer was evaluated. The final synthesized material cRGD-GdIO-DTX actively targeted αvβ3 on the surface of Panc-1 pancreatic cancer cells. Compared with conventional passive targeting, the enrichment of cRGD-GdIO-DTX in tumor tissues improved, and the diagnostic accuracy was significantly enhanced. Moreover, the acidic tumor microenvironment triggered the release of DTX from cRGD-GdIO-DTX, thus achieving tumor treatment. The inhibition of the proliferation of SW1990 and Panc-1 pancreatic cancer cells by cRGD-GdIO-DTX was much stronger than that by the untargeted GdIO-DTX and free DTX in vitro. In addition, in a human pancreatic cancer xenograft model, cRGD-GdIO-DTX considerably slowed tumor development and demonstrated excellent magnetic resonance enhancement. Our results suggest that cRGD-GdIO-DTX has potential applications for the precise diagnosis and efficient treatment of pancreatic cancer.

A pH-Responsive Nanoplatform Based on Magnetic Mesoporous Silica Nanoparticles for Enhanced Treatment of Pancreatic Cancer

“…Finally, the biocompatibility of M-MSN was assessed using a hemolysis assay. As shown in Figure B, the hemolysis rate was below 5% in all concentrations, which meets the hemolysis requirement for biomaterials. , …”

“…As shown in Figure 5B, the hemolysis rate was below 5% in all concentrations, which meets the hemolysis requirement for biomaterials. 40,41 Healthy Balb/c nude mice were then injected with M-MSN (mg/kg) or a 0.9% NaCl solution, respectively, to assess biotoxicity in vivo. This was quantified by measuring the change in the body weight of animals over a period of 7 days.…”

A Novel pH-Responsive Iron Oxide Core-Shell Magnetic Mesoporous Silica Nanoparticle (M-MSN) System Encapsulating Doxorubicin (DOX) and Glucose Oxidase (Gox) for Pancreatic Cancer Treatment

“…The DLS measurements are larger than the TEM results, which is attributed to the hydration layer around the particle surface in aqueous solution. 36 , 41 , 42 The particle size of the DG@NPs was larger than that of the M-MSNs, which might be due to the PDA coating. Moreover, The polydispersity index (PDI) of DG@NPs (0.31) was marginally lower than that of M-MSNs (0.36), implying that the PDA coating may have modestly improved the dispersion stability of DG@NPs ( Figure 2B and C ).…”