Enhanced theragnostic effect of ultrasound-mediated dual-targeted nanosystems based on phase-changeable polymeric nanodroplets for breast cancer

Targeted theranostic can detective tumors, raise the antitumor effects and reduce the side effects. Utilizing the tumor targeted cRGD ligand and phase-changeable perfluorohexane, a novel dual-targeted theranostical ultrasound contrast agent (DTTUCA): cyclo (Arg-Gly-Asp-d-Tyr-Lys) peptides (cRGD) modified poly(ethyleneglycol)-poly(caprolactone) (cRGD-PEG-PCL) @ doxorubicin (DOX) (cRGD-PEG-PCL@DOX) was constructed by the self-assembly and ultrasonic emulsification resulting in enhanced efficiency of sonography and anticancer in vitro and in vivo. The morphological measurements showed that DTTUCA was critical spherical nanodroplet (ca. (363.1±43.0) nm in diameter), which could mainly keep its size and shape for two weeks at 4 ?. Benefiting from the active and positive targeted, DTTUCA group displayed much higher cellular uptake (about 4 folders) and much lower cell viability than that of DOX against the breast cancer (BC) cells. In vitro, DTTUCA showed enhanced ultrasound (US)-mediated cavitation and highly US image intensity (ca. (54.2±5.7) dB) when the MI was 0.21 and fundamental frequency was 15 MHz at 37 ?. Meanwhile, a significant enhancement (US image intensity ca. (45.1±1.4) dB) of the US images was found in the kidney and heart after the tail intravenous, and tumor after in situ injection which could hold the enhanced effect even 90 min later. And, combining with 2-min radiation of low intensity focused ultrasound (LIFU), DTTUCA group got the best antitumor effect of all the five experimental groups, and the average tumor size in DTTUCA group was only (33.0±4.8) percent of that in saline group. Altogether, DTTUCA realized RGD and US mediated dual-targeted antitumor and enhanced US sonography, which had a great potential to promote US-based personalization targeted theragnostic of BC.

Na Li, was born in Zhoukou City, Henan Province, China. She is an associate professor in Henan Institute of Medical and Pharmaceutical Sciences of Zhengzhou University. She received her bachelor’s degree, master’s degree and Doctor’s degree from East China Normal University. Her research interest includes polymer-based drug delivery system and the application of biopolymer materials in medical.