Mesoporous composite nanoparticles for dual-modality ultrasound/magnetic resonance imaging and synergistic chemo-/thermotherapy against deep tumors

Abstract

High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment for solid tumors, which has been explored for potential clinical applications. However, the clinical applications of HIFU for large and deep tumors such as hepatocellular carcinoma (HCC) are severely limited by unsatisfactory imaging guidance, long therapeutic times, and damage to normal tissue around the tumor due to the high power applied. In this study, we developed doxorubicin/perfluorohexane-encapsulated hollow mesoporous Prussian blue nanoparticles (HMPBs-DOX/PFH) as theranostic agents, which can effectively guide HIFU therapy and enhance its therapeutic effects in combination with chemotherapy, by decreasing the cavitation threshold. We investigated the effects of this agent on ultrasound and magnetic resonance imaging in vitro and in vivo. In addition, we showed a highly efficient HIFU therapeutic effect against HCC tumors, as well as controlled drug release, owing to the phase-transitional performance of the PFH. We therefore conclude that HMPB-DOX/PFH is a safe and efficient nanoplatform, which holds significant promise for cancer theranostics against deep tumors in clinical settings.

Fundamentals and applications of nanoparticles for ultrasound‐based imaging and therapy

“…Hollow mesoporous Prussian blue NPs encapsulated with DOX/PFH could exhibit US/MR imaging and simultaneously increase the efficacy of HIFU treatment by decreasing the cavitation threshold. [ 24 ] Hollow MSNs functionalized with paramagnetic MnOx NPs have been demonstrated to exhibit effective MR imaging and simultaneous enhanced HIFU ablation capability. [ 145 ] Mesoporous silica nanocapsules (MSNCs) encapsulated with temperature‐sensitive biocompatible PFH could enlarge the ablation volume on bovine liver tissues at 120 W for 5 s when compared with that of the system only employing MSNCs or the PBS control.…”

“…[ 2 ] US imaging can be used for guiding the US therapeutic process and monitoring the efficiency of therapy for cancer and other serious diseases. Additionally, US also has relevant physicochemical properties for therapeutic applications, such as sonodynamic therapy (SDT), [ 22,23 ] high‐intensity focused US (HIFU), [ 24‐28 ] US‐triggered drug release and US‐enhanced gene transfection. [ 29‐32 ] Therefore, NP‐based US imaging and therapeutic modalities have been widely used in the clinic (Figure 2).…”

Cerasome-based gold-nanoshell encapsulating L-menthol for ultrasound contrast imaging and photothermal therapy of cancer

“…Briefly, to develop the CT-26 tumor model, 5×10 6 CT-26 cells in 100 ml PBS solution were subcutaneously injected into the right flank of mice. Animal experiments were carried on the 7-10th d after CT-26 cells implantation, once tumor had approached a size of 50-70 mm 3 . The CT-26 tumor model is a kind of solid tumor, has spherical nodular, complete envelope, non-invasive growth, fish-like section and high permeability of particles [33].…”

“…BALB/c mice were randomly divided into four groups: (1) normal saline (NS) only; (2) NS with laser; (3) GNC-LM only; (4) GNC-LM with laser. Treatments were initiated until the size of the tumor reached 100-200 mm 3 . Then, the mice were anesthetized with injection of 3% sodium of pentobarbital intraperitoneal and intravenously injected via the tail vein with the same dose of NS and GNC-LM (5 mg ml −1 ).…”

“…Molecular imaging has attracted tremendous research interest in recent years for its advantages in providing in vivo information for diagnosis [1][2][3]. Among various imaging techniques, ultrasound imaging has been widely applied due to its favorable features of real-time operation, low cost, portability and painfree operation for patients [4][5][6][7].…”