Suppressing Pancreatic Cancer Survival and Immune Escape via Nanoparticle-Modulated STING/STAT3 Axis Regulation.

Pancreatic ductal adenocarcinoma (PDAC) poses a challenge in oncology due to its high lethality and resistance to immunotherapy. Recently, emerging research on the stimulator of interferon gene (STING) pathway offers novel opportunities for immunotherapy. Although STING expression is retained in PDAC cells, the response of PDAC cells to STING agonists remains ineffective.

Photodynamically Tumor Vessel Destruction Amplified Tumor Targeting of Nanoparticles for Efficient Chemotherapy.

Efficient tumor-targeted drug delivery is still a challenging and currently unbreakable bottleneck in chemotherapy for tumors. Nanomedicines based on passive or active targeting strategy have not yet achieved convincing chemotherapeutic benefits in the clinic due to the tumor heterogeneity. Inspired by the efficient inflammatory-cell recruitment to acute clots, we constructed a two-component nanosystem, which is composed of an RGD-modified pyropheophorbide-a (Ppa) micelle (PPRM) that mediates the tumor vascular-targeted photodynamic reaction to activate local coagulation and subsequently transmits the coagulation signals to the circulating clot-targeted CREKA peptide-modified camptothecin (CPT)-loaded nanodiscs (CCNDs) for amplifying tumor targeting.

Manipulating Redox Homeostasis of Cancer Stem Cells Overcome Chemotherapeutic Resistance through Photoactivatable Biomimetic Nanodiscs.

Tumor heterogeneity remains a significant obstacle in cancer therapy due to diverse cells with varying treatment responses. Cancer stem-like cells (CSCs) contribute significantly to intratumor heterogeneity, characterized by high tumorigenicity and chemoresistance. CSCs reside in the depth of the tumor, possessing low reactive oxygen species (ROS) levels and robust antioxidant defense systems to maintain self-renewal and stemness.

Manipulating Neovasculature-Targeting Capability of Biomimetic Nanodiscs for Synergistic Photoactivatable Tumor Infarction and Chemotherapy.

Tumor infarction therapy is a promising antitumor strategy with the advantages of taking a short therapy duration, less risk of resistance, and effectiveness against a wide range of tumor types. However, its clinical application is largely hindered by tumor recurrence in the surviving rim and the potential risk of thromboembolic events due to nonspecific vasculature targeting. Herein, a neovasculature-targeting synthetic high-density lipoprotein (sHDL) nanodisc loaded with pyropheophorbide-a and camptothecin (CPN) was fabricated for photoactivatable tumor infarction and synergistic chemotherapy.

Major Strategies for Spatial Control of Ultrasound-Driven Gene Expression to Enhance Therapeutic Specificity.

A major challenge of gene therapy is to achieve highly specific transgene expression in tissues of interest with minimized off-target expression. Ultrasound in combination with microbubbles can transiently increase permeability of desired cells or tissues and thereby facilitate gene transfer. This kind of ultrasound-driven transgene expression has gained increasing attention due to its deep tissue penetration and high spatiotemporal resolution.

Enhancing Photodynamic Therapy Efficacy Against Cancer Metastasis by Ultrasound-Mediated Oxygen Microbubble Destruction to Boost Tumor-Targeted Delivery of Oxygen and Renal-Clearable Photosensitizer Micelles.

Hypoxic tumor microenvironment and nonspecific accumulation of photosensitizers are two key factors that limit the efficacy of photodynamic therapy (PDT). Herein, a strategy of oxygen microbubbles (MBs) boosting photosensitizer micelles is developed to enhance PDT efficacy and inhibit tumor metastasis by self-assembling renal-clearable ultrasmall poly(ethylene glycol)-modified protoporphyrin IX micelles (PPM) and perfluoropentane (PFP)-doped oxygen microbubbles (OPMBs), followed by ultrasound imaging-guided OPMB destruction to realize the tumor-targeted delivery of PPM and oxygen in tumor. Doping PFP into oxygen MBs increases the production of MBs and stability of oxygen MBs, allowing for persistent circulation in blood.

Stable flow-induced expression of KLK10 inhibits endothelial inflammation and atherosclerosis.

Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (), while regions exposed to stable flow () are protected. The proatherogenic and atheroprotective effects of and are mediated in part by the global changes in endothelial cell (EC) gene expression, which regulates endothelial dysfunction, inflammation, and atherosclerosis. Previously, we identified kallikrein-related peptidase 10 (, a secreted serine protease) as a flow-sensitive gene in mouse arterial ECs, but its role in endothelial biology and atherosclerosis was unknown.

Photosensitizer Nanoparticles Boost Photodynamic Therapy for Pancreatic Cancer Treatment.

Patients with pancreatic cancer (PCa) have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic. Yet, it suffers from certain limitations during clinical exploitation, including insufficient photosensitizers (PSs) delivery, tumor-oxygenation dependency, and treatment escape of aggressive tumors.

Key considerations in designing CRISPR/Cas9-carrying nanoparticles for therapeutic genome editing.

CRISPR-Cas9, the breakthrough genome-editing technology, has emerged as a promising tool to prevent and cure various diseases. The efficient genome editing technology strongly relies on the specific and effective delivery of CRISPR/Cas9 cargos. However, the lack of a safe, specific, and efficient non-viral delivery system for in vivo genome editing remains a major limit for its clinical translation.

Intraoperative Identification and Guidance of Breast Cancer Microfoci Using Ultrasound and Near-Infrared Fluorescence Dual-Modality Imaging.

The traditional method of labeling the nonpalpable breast cancer is placing a guidewire or metal marker guided by ultrasound or stereographic mammogram prior to surgery. However, the wire localization has a risk of displacement and could be an obstacle in the surgical course. To avoid these issues, we tried to combine the near-infrared (NIR) fluorescence dye dioctadecyltetramethyl indotricarbocyanine iodide (DiR) and microbubbles (MBs) to realize the dual-modality imaging for breast cancer microfoci intraoperative identification and guidance as a more efficient workflow.

Bioluminescence Imaging of Inflammation in Vivo Based on Bioluminescence and Fluorescence Resonance Energy Transfer Using Nanobubble Ultrasound Contrast Agent.

Inflammation is an immunological response involved in various inflammatory disorders ranging from neurodegenerative diseases to cancers. Luminol has been reported to detect myeloperoxidase (MPO) activity in an inflamed area through a light-emitting reaction. However, this method is limited by low tissue penetration and poor spatial resolution.

Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood-brain barrier.

Background And Purpose: Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) can safely open the blood-brain barrier (BBB) and target activated microglia for inflammatory area in the later stage of ischemia reperfusion.

Multicolor nanobubbles for FRET/ultrasound dual-modal contrast imaging.

The aim of this paper is to develop a novel fluorescence/ultrasound dual-modal contrast agent. We prepared multicolor nanobubbles by doping with three fluorescent dyes for combined fluorescence and contrast enhanced ultrasound imaging. The nanobubbles based on fluorescence resonance energy transfer (FRET) with different doping dye ratio combinations exhibited multiple colors under single wavelength excitation, allowing multiplexed assays for various biomedical applications.

Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.

To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of CF. Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for PDT, while amino groups could adsorb siRNA through electrostatic interaction for FOXA1 KD, which could inhibit the proliferation of estrogen-dependent ER+ BC.

Nano-sized Indocyanine Green J-aggregate as a One-component Theranostic Agent.

The development of biocompatiable efficient photothermal coupling agent (PCA) for image-guided photothermal therapy of cancer has gained increasing interests in recent years. Although various PCAs have been developed, the clinical translations of these materials have been largely hindered by the potential biosafety issues and challenges of scaling-up manufactures. In this research, we proposed nano-sized indocyanine green (ICG) J-aggregate (IJA) as a promising PCA which is fabricated by a very facile method using clinical-approved ICG as the only excipient.

(177)Lu-Labeled Cerasomes Encapsulating Indocyanine Green for Cancer Theranostics.

This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG2000-DOTA), followed by chelating radioisotope of (177)Lu. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer.

Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy.

The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity.

Doping hydroxylated cationic lipid into PEGylated cerasome boosts in vivo siRNA transfection efficacy.

The therapeutic application of small interfering RNA (siRNA) requires safe nanocarriers for specific and efficient delivery in vivo. Herein, PEGylated cationic cerasomes (PCCs) were fabricated by doping a cationic lipid with a hydroxyl group into nanohybrid cerasomes. Multiple properties of PCCs provide a solution to many of the limitations associated with current platforms for the delivery of siRNA.