Sonodynamic
therapy (SDT), a promising alternative for cancer therapy, utilizes
a sonosensitizer combined with ultrasound (US) irradiation to damage
tumor cells/tissues for therapeutic purposes. The ability of sonosensitizers
to specifically accumulate in tumor cells/tissues could greatly influence
their therapeutic efficiency. In this work, we report the use of US-activated
sonosensitizer (IR780)-based nanodroplets (IR780-NDs) for SDT, which
provide numerous benefits for killing cancer cells compared with traditional
methods. For instance, IR780-NDs showed effective surface-to-core
diffusion both in vitro and in vivo. In the presence of US, the acoustic
droplet vaporization (ADV) effect significantly assisted the conveyance
of IR780-NDs from the circulatory system to tumor regions, and the
acoustic wave force also increased the penetration depth within tumor
tissues. Furthermore, IR780-NDs possesses mitochondrial targeting
capabilities, which improves the precision and accuracy of SDT delivery.
During the in vitro assessment, the overproduction of reactive oxygen
species (ROS) was observed following mitochondrial targeting, which
rendered cancer cells more susceptible to ROS-induced apoptosis. Additionally,
IR780-ND is a suitable candidate for photoacoustic and fluorescence
imaging and can also enhance US imaging because of the ADV-generated
bubbles, which provides the potential for SDT guidance and monitoring.
Therefore, with combined modalities, IR780-NDs can be a promising
theranostics nanoplatform for cancer therapy.
Phototherapy has emerged as a novel therapeutic modality for cancer treatment, but its low therapeutic efficacy severely hinders further extensive clinical translation and application. This study reports amplifying the phototherapeutic efficacy by constructing a near‐infrared (NIR)‐responsive multifunctional nanoplatform for synergistic cancer phototherapy by a single NIR irradiation, which can concurrently achieve mitochondria‐targeting phototherapy, synergistic photothermal therapy (PTT)/photodynamic therapy (PDT), self‐sufficient oxygen‐augmented PDT, and multiple‐imaging guidance/monitoring. Perfluorooctyl bromide based nanoliposomes are constructed for oxygen delivery into tumors, performing the functions of red blood cells (RBCs) for oxygen delivery (“Nano‐RBC” nanosystem), which can alleviate the tumor hypoxia and enhance the PDT efficacy. The mitochondria‐targeting performance for enhanced and synergistic PDT/PTT is demonstrated as assisted by nanoliposomes. In particular, these “Nano‐RBCs” can also act as the contrast agents for concurrent computed tomography, photoacoustic, and fluorescence multiple imaging, providing the potential imaging capability for phototherapeutic guidance and monitoring. This provides a novel strategy to achieve high therapeutic efficacy of phototherapy by the rational design of multifunctional nanoplatforms with the unique performances of mitochondria targeting, synergistic PDT/PTT by a single NIR irradiation (808 nm), self‐sufficient oxygen‐augmented PDT, and multiple‐imaging guidance/monitoring.
Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genomewide association study, is positively correlated with the editing level of SLC22A3. Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals.RNA editing | metastasis suppressor | familial ESCC | SLC22A3 | ADAR2
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.