Abstract
A new class of multifunctional nanobubble using poly(lactic-co-glycolic acid) (PLGA) has been developed as ultrasound imaging contrast agents, doxorubicin carriers, and enhancers of ultrasound-mediated drug delivery. The doxorubicin nanobubble (DOX-NB) wrapping carbon tetrafluoride gas was prepared with double emulsion method. We evaluated the enhanced ultrasonic function of the DOX-NB in vivo; its antitumor function was confirmed. The diameter of the prepared bubble was 500 nm, and the potential was −23 mV. The drug loading and encapsulation efficiency of the bubble were 78.6 and 7.4 %, respectively. Therefore, the DOX-NB greatly enhanced ultrasound imaging in vivo. Ultrasound combined with DOX-NB had significant antitumor effect. Compared with other groups, the tumor growth rate and the proliferation index were the lowest while the survival rate and apoptosis index were the highest.
Highlights
The organ toxicity of conventional chemotherapeutic agents usually leads to relatively low level of drug concentration on target area of the body, limits the clinical use of chemotherapeutic drugs
Research has shown that the interval between vascular endothelial gap in a variety of tumors is between 380 and 780 nm [2, 3], and nanodrug carriers will not accumulate in normal tissue since normal tissue vascular connects more tightly with each other
We observed that the poly(lactic-co-glycolic acid) (PLGA) doxorubicin nanobubble (DOX-NB) could enhance the imaging of tumors under ultrasound and work as a drug carrier in ultrasound-mediated treatment
Summary
The organ toxicity of conventional chemotherapeutic agents usually leads to relatively low level of drug concentration on target area of the body, limits the clinical use of chemotherapeutic drugs. Many research teams are working on the research of ultrasound microbubble contrast agent imaging and therapeutic capabilities It has limitations, such as the cycle period of which is reduced significantly due to the dispersion of interior gas and the clearance function of body [12, 13]. The size of the microbubble is usually more than 1 μm, which limits its stay within the vascular system As a result, it cannot reach the tumor tissue area to truly achieve tumor imaging and therapy, restricting its tumor target imaging and therapy application [14]. We intended to introduce a new type of nanobubbles based on poly(lactic-co-glycolic acid) (PLGA) polymer wrapping doxorubicin and carbon tetrafluoride gas that could enhance ultrasound imaging of tumor and improve ultrasound-mediated therapeutic effect. We observed the tumor ultrasound imaging effects and therapeutic properties of loading DOX-NB applied in rabbit VX2 tumor
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