Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models.

Unlabelled: Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer-containing building blocks (∼94,000 photosensitizers per particle) and capable of potent PDT.

Deep learning for automatic organ and tumor segmentation in nanomedicine pharmacokinetics.

: Multimodal imaging provides important pharmacokinetic and dosimetry information during nanomedicine development and optimization. However, accurate quantitation is time-consuming, resource intensive, and requires anatomical expertise. : We present NanoMASK: a 3D U-Net adapted deep learning tool capable of rapid, automatic organ segmentation of multimodal imaging data that can output key clinical dosimetry metrics without manual intervention.

Novel Strategy to Drive the Intracellular Uptake of Lipid Nanoparticles for Photodynamic Therapy.

Nanoparticles' uptake by cancer cells upon reaching the tumor microenvironment is often the rate-limiting step in cancer nanomedicine. Herein, we report that the inclusion of aminopolycarboxylic acid conjugated lipids, such as EDTA- or DTPA-hexadecylamide lipids in liposome-like porphyrin nanoparticles (PS) enhanced their intracellular uptake by 25-fold, which was attributed to these lipids' ability to fluidize the cell membrane in a detergent-like manner rather than by metal chelation of EDTA or DTPA. EDTA-lipid-incorporated-PS (ePS) take advantage of its unique active uptake mechanism to achieve >95 % photodynamic therapy (PDT) cell killing compared to <5 % cell killing by PS.

Porphyrin-lipid stabilized paclitaxel nanoemulsion for combined photodynamic therapy and chemotherapy.

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), and ultrasmall porphyrin lipoproteins. Here, we used porphyrin-lipid to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel loaded in the oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) and chemotherapy in one platform.

Results: PTX (3.

A Radial Clutch Needle for Facile and Safe Tissue Compartment Access.

Efficient and safe access to targeted therapeutic sites is a universal challenge in minimally invasive medical intervention. Percutaneous and transluminal needle insertion is often performed blindly and requires significant user skill and experience to avoid complications associated with the damage of underlying tissues or organs. Here, we report on the advancement of a safer needle with a radial mechanical clutch, which is designed to prevent overshoot injuries through the automatic stopping of the needle once a target cavity is reached.

The dose threshold for nanoparticle tumour delivery.

Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements.

Guidelines for the experimental design of pharmacokinetic studies with nanomaterials in preclinical animal models.

A shared feature in the value proposition of every nanomaterial-based drug delivery systems is the desirable improvement in the disposition (or ADME) and pharmacokinetic profiles of the encapsulated drug being delivered. Remarkable progress has been made towards understanding the complex and multifactorial relationships between pharmacokinetic profiles and nanomaterial physicochemical properties, biological interactions, species physiology, etc. These advances have fuelled the rational design of numerous nanomaterials with long-circulation times and improved tissue accumulation (e.

Photodynamic therapy enables tumor-specific ablation in preclinical models of thyroid cancer.

The incidence of differentiated thyroid cancer has increased significantly during the last several decades. Surgical resection is the primary treatment for thyroid cancer and is highly effective, resulting in 5-year survival rates greater than 98%. However, surgical resection can result in short- and long-term treatment-related morbidities.

A Nanoemulsion with A Porphyrin Shell for Cancer Theranostics.

A nanoemulsion with a porphyrin shell (NewPS) was created by the self-assembly of porphyrin salt around an oil core. The NewPS system has excellent colloidal stability, is amenable to different porphyrin salts and oils, and is capable of co-loading with chemotherapeutics. The porphyrin salt shell enables porphyrin-dependent optical tunability.

Research tools for extrapolating the disposition and pharmacokinetics of nanomaterials from preclinical animals to humans.

A critical step in the translational science of nanomaterials from preclinical animal studies to humans is the comprehensive investigation of their disposition (or ADME) and pharmacokinetic behaviours. Disposition and pharmacokinetic data are ideally collected in different animal species (rodent and nonrodent), at different dose levels, and following multiple administrations. These data are used to assess the systemic exposure and effect to nanomaterials, primary determinants of their potential toxicity and therapeutic efficacy.

Evaluation of Novel Imaging Devices for Nanoparticle-Mediated Fluorescence-Guided Lung Tumor Therapy.

Background: Nonsurgical and minimally invasive approaches for early-stage peripheral lung cancer are needed to avoid the known morbidity of surgical resection, particularly in high-risk patients. We previously demonstrated the utility of multifunctional porphyrin-phospholipid nanoparticles (porphysomes) for fluorescence imaging and phototherapy after preferential accumulation into tumors. The objective of this study was to demonstrate the feasibility of porphysome-mediated imaging and photothermal therapy using a newly developed fiberscope and thoracoscope.

Mixed and Matched Metallo-Nanotexaphyrin for Customizable Biomedical Imaging.

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 and unique theranostics properties for biomedical applications. Unfortunately, there are significant difficulties associated with the synthesis of texaphyrin-based subunits capable of forming nanoparticles.

Author Correction: Towards an arthritis flare-responsive drug delivery system.

In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include support from the National Football League Players Association.

Towards an arthritis flare-responsive drug delivery system.

Local delivery of therapeutics for the treatment of inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares.

Rethinking translational nanomedicine: insights from the 'bottom-up' design of the Porphysome for guiding the clinical development of imageable nanomaterials.

Progress in therapeutics and biotechnologies leveraging new insights in our understanding of cancer biology and progression have had an underwhelming clinical significance thus far. A key challenge arising from the creation of nanomedicines consolidating multiple desirable functionalities into a 'all-in-one' platform is that the layering of functionalities into a single agent introduces novel complexities that significantly impede clinical translation. An alternative design approach seeks to exploit intrinsically multi-functional building block to assemble nanomedicines from the bottom-up, yielding agents with a multiplicity of radiologic, pharmacologic, and therapeutic properties derived from a single constituent.