Ultrasound-Mediated Cancer Therapeutics Delivery using Micelles and Liposomes: A Review.

BACKGROUND: Existing cancer treatment methods have many undesirable side effects that greatly reduce the quality of life of cancer patients. OBJECTIVE: This review will focus on the use of ultrasound-responsive liposomes and polymeric micelles in cancer therapy. METHODS: This review presents a survey of the literature regarding ultrasound-triggered micelles and liposomes using articles recently published in various journals, as well as some new patents in this field. RESULTS: Nanoparticles have proven promising as cancer theranostic tools. Nanoparticles are selective in nature, have reduced toxicity, and controllable drug release patterns making them ideal carriers for anticancer drugs. Numerous nanocarriers have been designed to combat malignancies, including liposomes, micelles, dendrimers, solid nanoparticles, quantum dots, gold nanoparticles, and, more recently, metal-organic frameworks. The temporal and spatial release of therapeutic agents from these nanostructures can be controlled using internal and external triggers, including pH, enzymes, redox, temperature, magnetic and electromagnetic waves, and ultrasound. Ultrasound is an attractive modality because it is non-invasive, can be focused on the diseased site, and has a synergistic effect with anticancer drugs. CONCLUSION: The functionalization of micellar and liposomal surfaces with targeting moieties and the use of ultrasound as a triggering mechanism can help improve the selectivity and enable the spatiotemporal control of drug release from nanocarriers.

Extracellular matrix remodeling associated with bleomycin-induced lung injury supports pericyte-to-myofibroblast transition.

Of the many origins of pulmonary myofibroblasts, microvascular pericytes are a known source. Prior literature has established the ability of pericytes to transition into myofibroblasts, but provide limited insight into molecular cues that drive this process during lung injury repair and fibrosis. Fibronectin and RGD-binding integrins have long been considered pro-fibrotic factors in myofibroblast biology, and here we test the hypothesis that these known myofibroblast cues coordinate pericyte-to-myofibroblast transitions. Specifically, we hypothesized that αvß3 integrin engagement on fibronectin induces pericyte transition into myofibroblastic phenotypes in the murine bleomycin lung injury model. Myosin Heavy Chain 11 (Myh11)-CreERT2 lineage tracing in transgenic mice allows identification of cells of pericyte origin and provides a robust tool for isolating pericytes from tissues for further evaluation. We used this murine model to track and characterize pericyte behaviors during tissue repair. The majority of Myh11 lineage-positive cells are positive for the pericyte surface markers, PDGFRß (55%) and CD146 (69%), and display typical pericyte morphology with spatial apposition to microvascular networks. After intratracheal bleomycin treatment of mice, Myh11 lineage-positive cells showed significantly increased contractile and secretory markers, as well as αv integrin expression. According to RNASeq measurements, many disease and tissue-remodeling genesets were upregulated in Myh11 lineage-positive cells in response to bleomycin-induced lung injury. In vitro, blocking αvß3 binding through cycloRGDfK prevented expression of the myofibroblastic marker αSMA relative to controls. In response to RGD-containing provisional matrix proteins present in lung injury, pericytes may alter their integrin profile.

Ultrasound-Triggered Immunotherapy for Cancer Treatment: An Update.

Over the past few decades, immunotherapy has emerged as a promising therapeutic approach to treat some types of cancer. Moreover, antibody-based cancer therapies can trigger apoptosis and cell growth inhibition to induce immune cell destruction of target cells through antibody-dependent cellular cytotoxicity (ADCC). Nevertheless, immunotherapeutic efficiency is often restricted due to deficient delivery or low accumulation of therapeutic molecules at the tumor site. The development of pegylated liposomes with monoclonal antibodies conjugated to their surfaces (immunoliposomes) and triggered with ultrasound can effectively improve drug accessibility by enhancing cell membrane permeability and drug release. This review summarizes existing traditional cancer treatments and their limitations, emphasizing the recent advancements in ultrasound-triggered immunotherapy.