Abstract
Perfluorooctyl bromide (PFOB) enclosed nanoparticles (NPs) as ultrasonic contrasts have shown promising results in the recent years. However, NPs display poor contrast enhancement in vivo. In this work, we used the copolymers poly(lactide-co-glycolide) carboxylic acid (PLGA-COOH) and poly(lactide-co- glycolide) poly(ethylene glycol) carboxylic acid (PLGA-PEG-COOH) as a shell to encapsulate PFOB to prepare a nanoultrasonic contrast agent. The NPs were small and uniform (210.6 ± 2.9 nm with a polydispersity index of 0.129 ± 0.016) with a complete shell nuclear structure under the transmission electron microscopy (TEM). In vitro, when concentration of NPs was ≥10 mg/ml and clinical diagnostic frequency was ≥9 MHz, NPs produced intensive enhancement of ultrasonic gray-scale signals. NPs could produce stable and obvious gray enhancement with high mechanical index (MI) (MI > 0.6). In vivo, the NPs offered good ultrasound enhancement in tumor after more than 24 h and optical imaging also indicated that NPs were mainly located at tumor site. Subsequent analysis confirmed that large accumulation of fluorescence was observed in the frozen section of the tumor tissue. All these results caused the conclusion that NPs encapsulated PFOB has achieved tumor-selective imaging in vivo.
Highlights
In recent years, ultrasonic molecular imaging has become a promising method for cancer diagnostics because it can image an intact living body at cellular and subcellular level with high spatial and temporal resolution, low cost, portability, and lack of ionizing irradiation [1]
The chemical composition of the synthesized product was confirmed by 1H-NMR (Figure 2)
The results showed that the enhancement induced by NPs (AUC = 46.46 ± 5.92) was significantly stronger than the enhancement induced by the microparticles encapsulated PFOB (MPs) (AUC = 8.24 ± 6.45, P = 0.001)
Summary
Ultrasonic molecular imaging has become a promising method for cancer diagnostics because it can image an intact living body at cellular and subcellular level with high spatial and temporal resolution, low cost, portability, and lack of ionizing irradiation [1]. Ultrasound contrast agents (UCAs) are necessary for ultrasound molecular imaging, and they can improve the accuracy and sensitivity of ultrasound diagnosis [2]. The contrast agents in the market consist of gas-encapsulated phospholipids or albumin (1 to 8 microns) [3]. Most tumors have porous vasculature with fenestrations between 380 and 780 nm [4]. The micro-sized UCAs are often limited by their lack of efficient penetration. To overcome this limitation, decreasing the UCA size to nanometer range would make UCA more likely to penetrate into tumor tissue
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