Anti-cancer And Ultrasound Imaging Of PLGA Ultrasound Nanobubbles With Co-delivery Of Gene And Drugs

Recently, cancer becomes one of chief diseases to threat the health of human, and chemotherapy is the major chose for cancer patients. However, multidrug resistance(MDR) remains a main barrier to the success of anticancer chemotherapy. As a result, how to reverse MDR is a key for cancer treatment. With the development of ultrasound imaging, combination of ultrasound diagnosis and targeting drug delivery system to reverse MDR supplies the possibility to reverse MDR, which opens us a new way for the cancer treatment. Ultrasound imaging has been widely applied to diagnose diseases,due to the advantage of noninvasive, inexpensive, real time and no ionizing. As an effective echo enhancer during ultrasound imaging, ultrasound contrast agent(UCA) has good applications in molecular imaging, cancer diagnosis, and thrombus treatment. Moreover, UCA can also acts as a drug or gene to improve drug or gene targeting delivery and reducing toxicity.In this study, DOX loaded nanobubbles were formulated by double emulsion using biodegradable high molecular polymer of PLGA(DOX-PLGA NBs). The NBs were demonstrated to be uniform(270 nm), dispersive and stable in water. It is found that the encapsulation efficiency and payload of DOX increased with its initial drug concentrations. The release behavior of DOX from the DOX-PLGA NBs exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release. The DOX-PLGA NBs also presented in a pH-triggered releasing profile, which showed greater anticancer to HeLa cell.To bind P-gp shRNA, complex NBs, namely DOX-PLGA/PEI/P-gp shNRA NBs, were prepared by incorporating PEI into DOX-PLGA NBs. The complex NBs with particle size of around 330 nm could completely protect gene against enzymatic degradation. The complex NBs could also release drug, which presented in a pH-triggered releasing profile. Biological study indicated that the complex NBs were taken up by MCF-7/ADR via the macropinocytosis pathway. Furthermore, the complex NBs exhibited satisfactory gene silencing effect, consequently promoted the uptake of DOX and increased cytotoxicity of DOX. As a result, the cancer cells were killed by overcoming MDR. Besides, Ultrasound experiments in vitro presented the ultrasound imaging ability. These results suggest that the complex NBs is promising in the area of cancer diagnosis and chemotherapy.