Doxorubicin nanobubble for combining ultrasonography and targeted chemotherapy of rabbit with VX2 liver tumor

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.

Keywords: Doxorubicin nanobubble (DOX-NB); Treatment; Ultrasound; VX2 liver tumor.

Fig. 1

a Light microscopy images of DOX-NB, b scanning electron microscopy (SEM) images of DOX-NB, c size distribution of DOX-NB by dynamic light scattering (DLS) measurement, and d potential distribution of DOX-NB by DLS measurement

Fig. 2

The release curve of DOX-NB between ultrasound and no ultrasound in vitro

Fig. 3

The time intensity curve of DOX-NB in the VX2 liver tumor

Fig. 4

Tumor growth curve of liver tumor

Fig. 5

The different expression of PCNA in each group using immunohistochemical staining. a Control group, b US group, c DOX group, d DOX-NB, and e DOX-NB + US group

Fig. 6

The proliferation index of each group VX2 liver tumor cell

Fig. 7

Cell apoptosis in each group VX2 liver tumor by TUNEL. a Control group, b US group, c DOX group, d DOX-NB, and e DOX-NB + US group

Fig. 8

Apoptotic index of VX2 liver tumor cells in each group

Fig. 9

KM survival curves of VX2 liver tumor cells in each group