Drug delivery by sonosensitive liposome and microbubble with acoustic-lens attached ultrasound: an in vivo feasibility study in a murine melanoma model.

Conventional chemotherapy methods have adverse off-target effects and low therapeutic efficiencies of drug release in target tumors. In this study, we proposed a combination therapy of doxorubicin (DOX)-loaded ultrasound (US)-sensitive liposomal nanocarriers (IMP301), microbubbles (MBs) under focused US exposure using convex acoustic lens-attached US (LENS) to tumor treatment. The therapeutic effects of each treatment in a murine melanoma model were evaluated using contrast-enhanced US (CEUS) and micro-computed tomography (micro-CT) imaging, bioluminescence and confocal microscopy imaging, and liquid chromatography-mass spectroscopy (LC/MS) analysis.

Development of a Polymersome-Based Nanomedicine for Chemotherapeutic and Sonodynamic Combination Therapy.

In anticancer therapy, combination therapy has been suggested as an alternative to the insufficient therapeutic efficacy of single therapy. Among combination therapies, combination chemo- and photodynamic therapy are actively investigated. However, photodynamic therapy shows a limitation in the penetration depth of the laser.

Evading Doxorubicin-Induced Systemic Immunosuppression Using Ultrasound-Responsive Liposomes Combined with Focused Ultrasound.

Doxorubicin (DOX) is a representative anticancer drug with a unique ability to induce immunogenic cell death of cancer cells. However, undesired toxicity on immune cells has remained a significant challenge, hindering the usage of DOX in cancer immunotherapy. Here, we report a combined therapy to avoid the off-target toxicity of DOX by adapting ultrasound-responsive liposomal doxorubicin and focused ultrasound exposure.

Enhanced delivery to brain using sonosensitive liposome and microbubble with focused ultrasound.

Glioblastoma is considered one of the most aggressive and dangerous brain tumors. However, treatment of GBM has been still challenged due to blood-brain barrier (BBB). BBB prevents that the chemotherapeutic molecules are extravasated to brain.

Effects of Lipid Shape and Interactions on the Conformation, Dynamics, and Curvature of Ultrasound-Responsive Liposomes.

We perform coarse-grained molecular dynamics simulations of bilayers composed of various lipids and cholesterol at their different ratios. Simulations show that cholesterol-lipid interactions restrict the lateral dynamics of bilayers but also promote bilayer curvature, indicating that these opposite effects simultaneously occur and thus cannot significantly influence bilayer stability. In contrast, lyso-lipids effectively pack the vacancy in the bilayer composed of cone-shaped lipids and thus reduce bilayer dynamics and curvature, showing that bilayers are more significantly stabilized by lyso-lipids than by cholesterol, in agreement with experiments.

Ultrasound-Responsive Liposomes for Targeted Drug Delivery Combined with Focused Ultrasound.

Chemotherapeutic drugs are traditionally used for the treatment of cancer. However, chemodrugs generally induce side effects and decrease anticancer effects due to indiscriminate diffusion and poor drug delivery. To overcome these limitations of chemotherapy, in this study, ultrasound-responsive liposomes were fabricated and used as drug carriers for delivering the anticancer drug doxorubicin, which was able to induce cancer cell death.

Early response evaluation of doxorubicin-nanoparticle-microbubble therapy in orthotopic hepatocellular carcinoma rat model using contrast-enhanced ultrasound and intravoxel incoherent motion-diffusion MRI.

Purpose: This study aimed to apply doxorubicin-loaded nanoparticle microbubble (Dox-NP-MB) therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) and investigate the utility of contrast-enhanced ultrasound (CEUS) and intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) for response evaluation.

Methods: Twenty-eight N1S1 HCC model rats were treated with either Dox-NP-MB (group [G] 1, n=8), doxorubicin (Dox) alone (G2, n=7), nanoparticle microbubbles alone (G3, n=7), or saline (G4, control, n=6) on days 0 and 7, and were sacrificed on day 11. IVIM-DWI and CEUS were performed before each treatment and before euthanasia.

Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary or secondary liver cancer. However, conventional TACE formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, a doxorubicin-loaded albumin nanoparticle-conjugated microbubble complex in an iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) has been developed as a new ultrasound-triggered TACE formulation.

Combined treatment of sorafenib and doxorubicin-loaded microbubble-albumin nanoparticle complex for hepatocellular carcinoma: A feasibility study.

Purpose: To assess the feasibility of the combined sorafenib (SOR) and doxorubicin-loaded microbubble-albumin nanoparticle complex (DOX-MAC) treatment effect in an orthotopic rat model of hepatocellular carcinoma (HCC).

Materials And Methods: Sixty-two rats with N1-S1 hepatoma were divided into four groups according to the treatment methods, i.e.

Combination Therapy with Doxorubicin-Loaded Reduced Albumin Nanoparticles and Focused Ultrasound in Mouse Breast Cancer Xenografts.

Because chemotherapeutic drugs are often associated with serious side effects, the central topic in modern drug delivery is maximizing the localization of drugs at the target while minimizing non-specific drug interactions at unwanted regions. To address this issue, biocompatible nanoparticles have been developed to enhance the drug half-life while minimizing the associated toxicity. Nevertheless, relying solely on the enhanced half-life and enhanced permeability and retention (EPR) effects has been ineffective, and designing stimulus-sensitive nanoparticles to introduce the precise control of drug release has been desired.

Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors.

Image-guided intra-arterial therapies play a key role in the management of hepatic malignancies. However, limited clinical outcomes suggest the need for new multifunctional drug delivery systems to enhance local drug concentration while reducing systemic adverse reactions. Therefore, we developed the albumin-doxorubicin nanoparticle conjugated microbubble (ADMB) to enhance therapeutic efficiency by sonoporation under exposure to ultrasound.

Multifunctional theranostic contrast agent for photoacoustics- and ultrasound-based tumor diagnosis and ultrasound-stimulated local tumor therapy.

Biomedical imaging-guided cancer therapy should have capabilities of both accurate tumor diagnosis and high therapeutic efficacy for the personalized treatment. Various biomedical imaging-guided cancer therapies are currently being investigated to overcome current limitations that include low sensitivity of diagnosis and poor drug delivery to the tumor site. Here, we report the development of a multifunctional theranostic contrast agent demonstrating high sensitive photoacoustic and ultrasound imaging and effective local delivery of anticancer drug to a tumor site.

Neuroprotective Effects of Human Serum Albumin Nanoparticles Loaded With Brimonidine on Retinal Ganglion Cells in Optic Nerve Crush Model.

Purpose: We investigated the neuroprotective effect of human serum albumin nanoparticles (HSA-NPs) and their conjugation with brimonidine (HSA-Br-NPs) on retinal ganglion cells (RGCs) in optic nerve crush (ONC) model.

Methods: We fabricated HSA-Br-NPs by ethanol precipitation, including 0.18% brimonidine (Br) and 3.

Therapeutic Ultrasound Contrast Agents for the Enhancement of Tumor Diagnosis and Tumor Therapy.

The functionality of ultrasound in early cancer detection is limited because of its relatively low contrast resolution. Because it has a high degree of echogenicity, a microbubble contrast agent is often used to overcome this intrinsic limitation of imaging at low-contrast resolution. A targeted and drug-loaded microbubble contrast agent for simultaneous diagnosis and therapy has recently been investigated.

Amplified photoacoustic performance and enhanced photothermal stability of reduced graphene oxide coated gold nanorods for sensitive photoacoustic imaging.

We report a strongly amplified photoacoustic (PA) performance of the new functional hybrid material composed of reduced graphene oxide and gold nanorods. Due to the excellent NIR light absorption properties of the reduced graphene oxide coated gold nanorods (r-GO-AuNRs) and highly efficient heat transfer process through the reduced graphene oxide layer, r-GO-AuNRs exhibit excellent photothermal stability and significantly higher photoacoustic amplitudes than those of bare-AuNRs, nonreduced graphene oxide coated AuNRs (GO-AuNRs), or silica-coated AuNR, as demonstrated in both in vitro and in vivo systems. The linear response of PA amplitude from reduced state controlled GO on AuNR indicates the critical role of GO for a strong photothermal effect of r-GO-AuNRs.

Photoacoustic-based nanomedicine for cancer diagnosis and therapy.

Photoacoustic imaging is the latest promising diagnostic modality that has various advantages such as high spatial resolution, deep penetration depth, and use of non-ionizing radiation. It also employs a non-invasive imaging technique and optically functionalized imaging. The goal of this study was to develop a nanomedicine for simultaneous cancer therapy and diagnosis based on photoacoustic imaging.

Narrow size distribution of microbubbles for enhancement of harmonic imaging.

An ultrasound microbubble contrast agent is a promising technique in clinical diagnosis because ultrasound in combination with microbubbles enhances the ultrasound backscatter to produce an increased contrast images. In this study, we developed phospholipid-based microbubbles showing a relatively narrow size distribution of 0.8-1.

The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection.

The purpose of this study is to determine the correlation between the distribution of nanoparticles in the vitreous and retina and their surface properties after intravitreal injection. For this purpose, we synthesized seven kinds of nanoparticles through self-assembly of amphiphilic polymer conjugates in aqueous condition. They showed similar size but different surface properties.