posted on 2021-04-22, 19:23authored byChao Li, Yao Lu, Lili Cheng, Xiaoge Zhang, Jun Yue, Jie Liu
As a noninvasive therapy, high-intensity
focused ultrasound (HIFU)
shows great potential in inducing anticancer immune responses. However,
the overall anticancer efficacy of HIFU is still limited due to the
rapid attenuation of ultrasound waves and inadequacy of ultrasound
waves to spread to the whole tumor. Here, we combined HIFU with the
ultrasound contrast agent/chemotherapeutic drug co-delivery nanodroplets
to achieve synergistic enhancement of anticancer efficacy. Different
from the widely used thermal HIFU irradiation, by which excessive
heating would result in inactivation of immune stimulatory molecules,
we used short acoustic pulses to trigger HIFU (mechanical HIFU, mHIFU)
to improve anticancer immune responses. The nanodroplets displayed
a mHIFU/glutathione (GSH)-dual responsive drug release property, and
their cellular uptake efficacy and toxicity against cancer cells increased
upon mHIFU irradiation. The generated immunogenic debris successfully
induced the exposure of damage-associated molecular patterns on the
cell surface for dendritic cells (DCs) maturation. In vivo experiments
with tumor-bearing mice showed that the co-delivery nanodroplets in
combination with mHIFU could effectively inhibit tumor growth by inducing
immunogenic cell death, activating DCs maturation, and enhancing the
effector T-cell infiltration within tumors. This work reveals that
combined treatment with nanodroplets and mHIFU is a promising approach
to eradicate tumors.