A5085958846- Nanoplatforms for cancer theranostics
- RNA Interference and Gene Delivery
- Photodynamic Therapy Research Studies
- Porphyrin and Phthalocyanine Chemistry
- Advanced biosensing and bioanalysis techniques
- Luminescence and Fluorescent Materials
- Lipid Membrane Structure and Behavior
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Nanoparticle-Based Drug Delivery
- Click Chemistry and Applications
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Advanced Fluorescence Microscopy Techniques
- Advanced Chemical Physics Studies
- Nanopore and Nanochannel Transport Studies
- CAR-T cell therapy research
- Surfactants and Colloidal Systems
- Radiation Therapy and Dosimetry
- Spectroscopy Techniques in Biomedical and Chemical Research
- Protein Interaction Studies and Fluorescence Analysis
- CRISPR and Genetic Engineering
- Protein purification and stability
University of British Columbia
2022-2024
Princess Margaret Cancer Centre
2018-2024
University Health Network
2018-2024
University of Hull
2017-2018
University College London
2017
Durham University
2017
The transfection potency of lipid nanoparticle (LNP) mRNA systems is critically dependent on the ionizable cationic component. LNP composed optimized lipids often display distinctive mRNA-rich "bleb" structures. Here, it shown that such structures can also be induced for LNPs containing nominally less active by formulating them in presence high concentrations pH 4 buffers as sodium citrate, leading to improved potencies both vitro and vivo. Induction bleb structure type buffer employed, with...
Abstract Organic building blocks are the centerpieces of “one‐for‐all” nanoparticle development. Herein, we report synthesis a novel aza‐BODIPY‐lipid block and its self‐assembly into liposomal (BODIPYsome). We observed optically stable NIR J‐aggregation within BODIPYsome that is likely attributed to J‐dimerization. BODIPYsomes with cholesterol showed enhanced colloidal stability while maintaining high extinction coefficient (128 m −1 cm ) fluorescence quenching (99.70±0.09 %), which enables...
Lipid nanoparticles (LNPs) for delivery of mRNA usually contain ionizable lipid/helper lipid/cholesterol/PEG-lipid in molar ratios 50:10:38.5:1.5, respectively. These LNPs are rapidly cleared from the circulation following intravenous (i.v.) administration, limiting uptake into other tissues. Here, we investigate properties LNP systems prepared with high levels "helper" lipids such as 1,2-distearoyl-sn-glycero-3-phosphorylcholine (DSPC) or N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine...
Lipid nanoparticles (LNPs) have achieved clinical success in delivering small interfering RNAs (siRNAs) for targeted gene therapy. However, endosomal escape of siRNA into the cytosol remains a fundamental challenge LNPs. Herein, we report strategy termed light-activated release (LASER) to address this challenge. We established porphyrin-LNP by incorporating porphyrin-lipids clinically approved Onpattro formulation. The maintained physical properties an LNP and generated reactive oxygen...
Lipid nanoparticle (LNP) formulations are a proven method for the delivery of nucleic acids gene therapy as exemplified by worldwide rollout LNP-based RNAi therapeutics and mRNA vaccines. However, targeting specific tissues or cells is still major challenge. After LNP administration, LNPs interact with biological fluids (i.e., blood), components which adsorb onto surface forming layer biomolecules termed “biomolecular corona (BMC)” affects stability, biodistribution, tissue tropism. The...
Abstract Background Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including liposome-like porphysome (aqueous-core), porphyrin nanodroplet (liquefied gas-core), ultrasmall lipoproteins. Here, we used porphyrin-lipid stabilize the water/oil interface nanoemulsions with paclitaxel loaded in oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) chemotherapy one...
Nanoparticles' uptake by cancer cells upon reaching the tumor microenvironment is often rate-limiting step in nanomedicine. Herein, we report that inclusion of aminopolycarboxylic acid conjugated lipids, such as EDTA- or DTPA-hexadecylamide lipids liposome-like porphyrin nanoparticles (PS) enhanced their intracellular 25-fold, which was attributed to these lipids' ability fluidize cell membrane a detergent-like manner rather than metal chelation EDTA DTPA. EDTA-lipid-incorporated-PS (ePS)...
Gadolinium (Gd3+)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given using nanovesicles improve its Herein, Gd-Tex transformed into building blocks "Gd-Tex-lipids" self-assemble called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of in single nanovesicle and achieving accumulation tumors. To elucidate the impact O2...
Abstract Organic building blocks are the centerpieces of “one‐for‐all” nanoparticle development. Herein, we report synthesis a novel aza‐BODIPY‐lipid block and its self‐assembly into liposomal (BODIPYsome). We observed optically stable NIR J‐aggregation within BODIPYsome that is likely attributed to J‐dimerization. BODIPYsomes with cholesterol showed enhanced colloidal stability while maintaining high extinction coefficient (128 m −1 cm ) fluorescence quenching (99.70±0.09 %), which enables...
Abstract Nanoparticles’ uptake by cancer cells upon reaching the tumor microenvironment is often rate‐limiting step in nanomedicine. Herein, we report that inclusion of aminopolycarboxylic acid conjugated lipids, such as EDTA‐ or DTPA‐hexadecylamide lipids liposome‐like porphyrin nanoparticles (PS) enhanced their intracellular 25‐fold, which was attributed to these lipids’ ability fluidize cell membrane a detergent‐like manner rather than metal chelation EDTA DTPA. EDTA‐lipid‐incorporated‐PS...
Exploitation of photosensitizers as payloads for antibody-based anticancer therapeutics offers a novel alternative to the small pool commonly utilized cytotoxins. However, existing bioconjugation methodologies are incompatible with requirement increased antibody loading without compromising function, stability, or homogeneity. Herein, we describe first application dendritic multiplier groups allow more than 4 porphyrins full IgG in site-specific and highly homogeneous manner. Photophysical...
Theranostic nanoparticles aim to integrate diagnostic imaging and therapy facilitate image-guided treatment protocols. Herein, we present a theranostic nanotexaphyrin for prostate-specific membrane antigen (PSMA)-targeted radionuclide focal photodynamic (PDT) accomplished through the chelation of metal isotopes (In, Lu). To realize nanotexaphyrin's properties, developed rapid robust
ADVERTISEMENT RETURN TO ISSUEPREVFirst ReactionsNEXTX-ray-Activatable Photodynamic NanoconstructsX-ray induced photodynamic therapy enables chemotherapy-free treatment of deep-tissue cancer with a low dose X-ray radiation.Marta OverchukMarta OverchukInstitute Biomaterials and Biomedical Engineering, University Toronto, 101 College Street, Ontario M5G 1L7, CanadaPrincess Margaret Cancer Centre, Health Network, PMCRT 5-354, CanadaMore by Marta Overchuk, Miffy H. Y. ChengMiffy ChengPrincess...
We herein report the synthesis and analysis of a novel aza-BODIPY-antibody conjugate, formed by controlled regioselective bioconjugation methodology. Employing clinically relevant antibody, which targets HER2 positive cancers, represents an excellent example antibody targeting strategy for this class near-IR emitting fluorophore. The NIR fluorescence binding properties were validated through in vitro studies using live cell confocal imaging.
Antimicrobial photodynamic therapy (aPDT) is an alternative to antibiotics that has potential for the treatment of chronic skin wounds, but requires improved, highly selective photosensitizer systems. Rhenium (Re)‐complex‐ and iridium (Ir)‐complex‐based phospholipid conjugates, as PDT‐functional building blocks liposomes, are presented, varying structural components proportion compounds explored, including adjusting cholesterol polyethylene glycol (PEG)‐lipid contents, incorporating...
Abstract The discovery and synthesis of multifunctional organic building blocks for nanoparticles have remained challenging. Texaphyrin macrocycles are multifunctional, all‐organic compounds that possess versatile metal‐chelation capabilities unique theranostics properties biomedical applications. Unfortunately, there significant difficulties associated with the texaphyrin‐based subunits capable forming nanoparticles. Herein, detailed a texaphyrin‐phospholipid block is reported via key...
A pH-driven self-assembly of a simple aza-BODIPY was discovered in PBS solution, whereby ion-specific J-aggregated nanostructures were generated at very low dye concentration (2.5–20 [Formula: see text]M). The aggregation process investigated different conditions (pH, temperature and time) by monitoring absorption spectral shifts associated nanostructure morphological changes. demonstrated an instantaneous thermodynamic phenomenon with three characteristic structures, each distinctive...
When formulating mRNA into lipid nanoparticles (LNP), various copy numbers of are encapsulated, leading to a distribution loading levels within LNPs. It is unclear if the level affects functional delivery message. Here we show that depending on level, LNPs exhibit distinct mass densities and can be fractionated via ultracentrifugation. Upon fractionation, investigated influence LNP sizing, composition morphology. We further conducted in vitro vivo found fraction with highest were least...