Fluorination of Aza-BODIPY for Cancer Cell Plasma Membrane-Targeted Imaging and Therapy.

Photodynamic therapy (PDT) holds great potential in cancer treatment, leveraging photosensitizers (PSs) to deliver targeted therapy. Fluorination can optimize the physicochemical and biological properties of PSs for better PDT performance. Here, we report some high-performance multifunctional PSs specifically designed for cancer PDT by fluorinating aza-BODIPY with perfluoro--butoxymethyl (PFBM) groups.

Nanoengineered Neutrophil as F-MRI Tracer for Alert Diagnosis and Severity Assessment of Acute Lung Injury.

Acute lung injury (ALI) is a severe complication in clinical settings. Alert diagnosis and severity assessment of ALI is pivotal to ensure curative treatment and increase survival rates. However, the development of a precise ALI diagnostic strategy remains a pending task.

Positron emission tomography guided synergistic treatment of melanoma using multifunctional zirconium-hematoporphyrin nanosonosensitizers.

Sonodynamic therapy (SDT) has emerged as a useful approach for tumor treatment. However, its widespread application is impeded by poor pharmacokinetics of existing sonosensitizers. Here we developed a metal-organic nanoplatform, wherein a small-molecule sonosensitizer (hematoporphyrin monomethyl ether, HMME) was ingeniously coordinated with zirconium, resulting in a multifunctional nanosonosensitizer termed Zr-HMME.

Tyrosine-Mutant AAV8 Vector Mediated Efficient and Safe Gene Transfer of Pigment Epithelium-Derived Factor to Mouse Lungs.

Background/aims: Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung.

Telmisartan Nanosuspension for Inhaled Therapy of COVID-19 Lung Disease and Other Respiratory Infections.

Vaccine hesitancy and the occurrence of elusive variants necessitate further treatment options for coronavirus disease 2019 (COVID-19). Accumulated evidence indicates that clinically used hypertensive drugs, angiotensin receptor blockers (ARBs), may benefit patients by mitigating disease severity and/or viral propagation. However, current clinical formulations administered orally pose systemic safety concerns and likely require a very high dose to achieve the desired therapeutic window in the lung.

A Two-Pronged Pulmonary Gene Delivery Strategy: A Surface-Modified Fullerene Nanoparticle and a Hypotonic Vehicle.

Inhaled gene therapy poses a unique potential of curing chronic lung diseases, which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically relevant gene transfer efficacy in the lung due to the presence of numerous biological delivery barriers. Here, we introduce a simple approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo.

Engineered Antibody Fragment against the Urokinase Plasminogen Activator for Fast Delineation of Triple-Negative Breast Cancer by Positron Emission Tomography.

The urokinase plasminogen activator (uPA) and its cofactors are important regulators of tumor initiation and progression (including metastasis), and its overexpression is associated with unfavorable situations in cancer patients. We have previously used positron emission tomography (PET) imaging with a radiolabeled monoclonal antibody against the uPA (named ATN-291) to detect the uPA signaling activity in various cancer types; however, good tumor contrast can only be observed 24 h postinjection. To shorten the antibody circulation time and decrease interactions of ATN-291 with the mononuclear phagocyte system (MPS), our goal in this study is to develop an engineered antibody fragment (F(ab')) from the parent antibody.

Enhancing nanoparticle penetration through airway mucus to improve drug delivery efficacy in the lung.

: Airway mucus gel layer serves as a key delivery barrier that limits the performance of inhaled drug delivery nanoparticles. Conventional nanoparticles are readily trapped by the airway mucus and rapidly cleared from the lung via mucus clearance mechanisms. These nanoparticles cannot distribute throughout the lung airways, long-reside in the lung and/or reach the airway epithelium.

Fullerene nanoparticles: a promising candidate for the alleviation of silicosis-associated pulmonary inflammation.

Chronic exposure to crystalline silica causes the development of silicosis, which is one of the most important occupational diseases worldwide. In the early stage of silicosis, inhaled silica crystals initiate oxidative stress, a cycle of persistent inflammation and lung injury. And it is crucial to prevent the deteriorative progression in the onset of the disease.

AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression.

There has been great progress in ocular gene therapy, but delivery of viral vectors to the retinal pigmented epithelium (RPE) and retina can be challenging. Subretinal injection, the preferred route of delivery for most applications, requires a surgical procedure that has risks. Herein we report a novel gene therapy delivery approach, suprachoroidal injection of AAV8 vectors, which is less invasive and could be done in an outpatient setting.

Positron Emission Tomography/Magnetic Resonance Imaging of Glioblastoma Using a Functionalized Gadofullerene Nanoparticle.

Water-soluble gadofullerene nanomaterials have been extensively investigated as magnetic resonance imaging (MRI) contrast agents, radical scavengers, sensitizers for photodynamic therapy, and inherent antineoplastic agents. Most recently, an alanine-modified gadofullerene nanoparticle (Gd@C-Ala) with excellent anticancer activity has been reported; however, the absolute tumor uptake of Gd@C-Ala is still far from being satisfactory, and its dynamic pharmacokinetics and long-term metabolic behaviors remain to be elucidated. Herein, Gd@C-Ala was chemically modified with eight-arm polyethylene glycol amine to improve its biocompatibility and provide the active sites for the attachment of a tumor-homing ligand (cRGD) and positron emission tomography (PET) isotopes (i.

Photo-triggered gadofullerene: enhanced cancer therapy by combining tumor vascular disruption and stimulation of anti-tumor immune responses.

Efficient treatment of primary tumor and preventing cancer metastasis present intriguing alternatives to cancer therapy. Herein, for the first time, we reported the photo-triggered nano-gadofullerene (Gd@C-Ala, abbreviated Gd-Ala) induced malignant tumor vascular disruption by shortening the light interval between Gd-Ala administration and light illumination, where oxygen in blood vessels was employed efficiently to produce cytotoxic reactive oxygen species (ROS). The produced ROS could not only destroy the tumor cells but also devastate the vascular endothelial cells corresponding to the loss of intercellular junctions and vessels disruption.

Biodegradable, Hydrogen Peroxide, and Glutathione Dual Responsive Nanoparticles for Potential Programmable Paclitaxel Release.

Reactive oxygen species (ROS) and glutathione (GSH) dual responsive nanoparticulate drug delivery systems (nano-DDSs) hold great promise to improve the therapeutic efficacy and alleviate the side effects of chemo drugs in cancer theranosis. Herein, hydrogen peroxide (HO) and GSH dual responsive thioketal nanoparticle (TKN) was rationally designed for paclitaxel (PTX) delivery. Compared to other stimuli-sensitive nano-DDSs, this dual responsive DDS is not only sensitive to biologically relevant HO and GSH for on-demand drug release but also biodegradable into biocompatible byproducts after fulfilling its delivering task.

In Vivo Targeting and Positron Emission Tomography Imaging of Tumor with Intrinsically Radioactive Metal-Organic Frameworks Nanomaterials.

Nanoscale metal-organic frameworks (nMOF) materials represent an attractive tool for various biomedical applications. Due to the chemical versatility, enormous porosity, and tunable degradability of nMOFs, they have been adopted as carriers for delivery of imaging and/or therapeutic cargos. However, the relatively low stability of most nMOFs has limited practical in vivo applications.

Antibody-based PET of uPA/uPAR signaling with broad applicability for cancer imaging.

Mounting evidence suggests that the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a central role in tumor progression. The goal of this study was to develop an 89Zr-labeled, antibody-based positron emission tomography (PET) tracer for quantitative imaging of the uPA/uPAR system. An anti-uPA monoclonal antibody (ATN-291) was conjugated with a deferoxamine (Df) derivative and subsequently labeled with 89Zr.

In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide.

Angiogenesis, i.e. the formation of neovasculatures, is a critical process during cancer initiation, progression, and metastasis.

A Versatile and Clearable Nanocarbon Theranostic Based on Carbon Dots and Gadolinium Metallofullerene Nanocrystals.

Nanocarbons such as carbon nanotubes, graphene derivatives, and carbon nanohorns have illustrated their potential uses as cancer theranostics owing to their intrinsic fluorescence or NIR absorbance as well as superior cargo loading capacity. However, some problems still need to be addressed, such as the fates and long-term toxicology of different nanocarbons in vivo and the improvement of their performance in various biomedical imaging-guided cancer therapy systems. Herein, a versatile and clearable nanocarbon theranostic based on carbon dots (CDs) and gadolinium metallofullerene nanocrystals (GFNCs) is first developed, in which GFNCs enhance the tumor accumulation of CDs, and CDs enhance the relaxivity of GFNCs, leading to an efficient multimodal imaging-guided photodynamic therapy in vivo without obvious long-term toxicity.

Fullerene/photosensitizer nanovesicles as highly efficient and clearable phototheranostics with enhanced tumor accumulation for cancer therapy.

A novel phototheranostic platform based on tri-malonate derivative of fullerene C70 (TFC70)/photosensitizer (Chlorin e6, Ce6) nanovesicles (FCNVs) has been developed for effective tumor imaging and treatment. The FCNVs were prepared from amphiphilic TFC70-oligo ethylene glycol -Ce6 molecules. The developed FCNVs possessed the following advantages: (i) high loading efficiency of Ce6 (up to ∼57 wt%); (ii) efficient absorption in near-infrared light region; (iii) enhanced cellular uptake efficiency of Ce6 in vitro and in vivo; (iv) good biocompatibility and total clearance out from the body.

Radioactive Nanomaterials for Multimodality Imaging.

Nuclear imaging techniques, including primarily positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can provide quantitative information for a biological event in vivo with ultra-high sensitivity, however, the comparatively low spatial resolution is their major limitation in clinical application. By convergence of nuclear imaging with other imaging modalities like computed tomography (CT), magnetic resonance imaging (MRI) and optical imaging, the hybrid imaging platforms can overcome the limitations from each individual imaging technique. Possessing versatile chemical linking ability and good cargo-loading capacity, radioactive nanomaterials can serve as ideal imaging contrast agents.

Synergistic Effect of Human Serum Albumin and Fullerene on Gd-DO3A for Tumor-Targeting Imaging.

A macromolecular magnetic resonance imaging (MRI) contrast agent was successfully synthesized by conjugating the gadolinium/1,4,7,10-tetraazacyclododecane-1,4,7-tetracetic acid complex (Gd-DO3A) with 6,6-phenyl-C61 butyric acid (PC61BA) and upon further modification with human serum albumin (HSA). The final product, PC61BA-(Gd-DO3A)/HSA, has a high stability and exhibits a much higher relaxivity (r1 = 89.1 mM(-1) s(-1) at 0.

Theranostic applications of carbon nanomaterials in cancer: Focus on imaging and cargo delivery.

Carbon based nanomaterials have attracted significant attention over the past decades due to their unique physical properties, versatile functionalization chemistry, and biological compatibility. In this review, we will summarize the current state-of-the-art applications of carbon nanomaterials in cancer imaging and drug delivery/therapy. The carbon nanomaterials will be categorized into fullerenes, nanotubes, nanohorns, nanodiamonds, nanodots and graphene derivatives based on their morphologies.

The positive influence of fullerene derivatives bonded to manganese(III) porphyrins on water proton relaxation.

Manganese-porphyrin compounds as MRI contrast agents have drawn particular attention due to high relaxivities and unique biodistribution. It has been reported that the charge density of the metal center and steric decompression of the substituents, rather than rotational correlation time, were the key factors to determine the relaxivities of manganese(III) porphyrins. In this study, [6,6]-phenyl-C61-butyric acid (PC61BA) was introduced into 5-(4-aminophenyl)-10,15,20-tris (4-sulfonatophenyl) porphyrin (APTSPP) to investigate the influence on water proton relaxation.

Amphiphilic trismethylpyridylporphyrin-fullerene (C) dyad: an efficient photosensitizer under hypoxia conditions.

Amphiphilic trismethylpyridylporphyrin-C (PC) dyad with improved photosensitization has been successfully prepared. The PC dyad forms a liposomal nanostructure through molecular self-assembling. An increased absorption coefficient in the visible region, good biocompatibility, and high photostability were observed on the self-assembling structure.

Formation of nitrogen-doped mesoporous graphitic carbon with the help of melamine.

An efficient and facile synthesis method of nitrogen-doped mesoporous graphitic carbon (NMGC) was reported with melamine as a nitrogen source and citric acid as a carbon source. By taking advantage of the functional groups on melamine and citric acid, a uniform mixture of these two components was obtained via a self-assembly process. Accordingly, the nitrogen-doped mesoporous graphitic carbon (NMGC) can be obtained by means of the high temperature treatment.

In vitro and in vivo photothermally enhanced chemotherapy by single-walled carbon nanohorns as a drug delivery system.

Single-walled carbon nanohorns (SWNHs) have exhibited many special advantages in biomedical applications. Herein, doxorubicin-loaded SWNHs (DOX-SWNHs) are prepared and further modified by amphiphilic deoxycholic acid modified-hydropropyl chitosan (DCA-HPCHS) to improve their biocompatibility. The obtained DOX-SWNH/DCA-HPCHS drug delivery system (DDS) possesses high stability in physiological media and excellent photothermal properties when exposed to laser irradiation in the near-infrared (NIR) region, which dramatically enhances the chemotherapy of DOX.