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.

Quantitative Pharmacokinetics Reveal Impact of Lipid Composition on Microbubble and Nanoprogeny Shell Fate.

Microbubble-enabled focused ultrasound (MB-FUS) has revolutionized nano and molecular drug delivery capabilities. Yet, the absence of longitudinal, systematic, quantitative studies of microbubble shell pharmacokinetics hinders progress within the MB-FUS field. Microbubble radiolabeling challenges contribute to this void.

Protease-Activatable Porphyrin Molecular Beacon for Osteoarthritis Management.

Despite the substantial burden posed by osteoarthritis (OA) globally, difficult challenges remain in achieving early OA diagnosis and adopting effective disease-modifying treatments. In this study, we use a biomolecular approach to address these limitations by creating an inherently theranostic molecular beacon whose imaging and therapeutic capabilities are activated by early pathological changes in OA. This platform comprised (1) a peptide linker substrate for metalloproteinase-13 (MMP-13), a pathological protease upregulated in OA, which was conjugated to (2) a porphyrin moiety with inherent multimodal imaging, photodynamic therapy, and drug delivery capabilities, and (3) a quencher that silences the porphyrin's endogenous fluorescence and photoreactivity when the beacon is intact.

Targeted Theranostic In/Lu-Nanotexaphyrin for SPECT Imaging and Photodynamic Therapy.

Theranostic nanoparticles aim to integrate diagnostic imaging and therapy to facilitate image-guided treatment protocols. Herein, we present a theranostic nanotexaphyrin for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and focal photodynamic therapy (PDT) accomplished through the chelation of metal isotopes (In, Lu). To realize nanotexaphyrin's theranostic properties, we developed a rapid and robust In/Lu-nanotexaphyrin radiolabeling method using a microfluidic system that achieved a high radiochemical yield (>90%).

Subtherapeutic Photodynamic Treatment Facilitates Tumor Nanomedicine Delivery and Overcomes Desmoplasia.

Limited tumor nanoparticle accumulation remains one of the main challenges in cancer nanomedicine. Here, we demonstrate that subtherapeutic photodynamic priming (PDP) enhances the accumulation of nanoparticles in subcutaneous murine prostate tumors ∼3-5-times without inducing cell death, vascular destruction, or tumor growth delay. We also found that PDP resulted in an ∼2-times decrease in tumor collagen content as well as a significant reduction of extracellular matrix density in the subendothelial zone.

Photophysics of J-Aggregating Porphyrin-Lipid Photosensitizers in Liposomes: Impact of Lipid Saturation.

Porphyrin aggregates have attractive photophysical properties for phototherapy and optical imaging, including quenched photosensitization, efficient photothermal conversion, and unique absorption spectra. Although hydrophobic porphyrin photosensitizers have long been encapsulated into liposomes for drug delivery, little is known about the membrane properties of liposomes with large amphiphilic porphyrin compositions. In this paper, a porphyrin-lipid conjugate was incorporated into liposomes formed of saturated or unsaturated lipids to study the membrane composition-dependent formation of highly ordered porphyrin J-aggregates and disordered aggregates.

Activating Drugs with Sound: Mechanisms Behind Sonodynamic Therapy and the Role of Nanomedicine.

Sonodynamic therapy (SDT) is a promising therapeutic platform for minimally invasive cancer treatment in which acoustically susceptible drug agents, sonosensitizers, are activated by deep-tissue-penetrating low frequency ultrasound. Despite growing research in recent years, the field has yet to clearly elucidate broadly applicable mechanisms by which acoustic cavitation triggers sonosensitizer therapeutic activity, creating difficulties in achieving substantial and translatable therapeutic efficacy. In this review, we will critically analyze the proposed mechanisms underlying SDT and overview how nanomedicines can complement and extend these mechanisms to deliver more efficacious SDT.

Tailoring Porphyrin Conjugation for Nanoassembly-Driven Phototheranostic Properties.

Lipoprotein mimetic nanostructures, which consist of an amphiphilic lipid shell, a hydrophobic core, and an apolipoprotein mimetic peptide, serve as a versatile platform for the design of drug delivery vehicles as well as the investigation of supramolecular assemblies. Porphyrin incorporation into biomimetic lipoproteins allows one to take advantage of the inherent multimodal photophysical properties of porphyrins, yielding various fluorescence, photoacoustic, and photodynamic agents. To facilitate their incorporation into a lipoprotein structure, porphyrins have been conjugated through a variety of strategies.

Targeting SR-BI for Cancer Diagnostics, Imaging and Therapy.

Scavenger receptor class B type I (SR-BI) plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumors and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents.

Multimodal micro, nano, and size conversion ultrasound agents for imaging and therapy.

Ultrasound (US) is one of the most commonly used clinical imaging techniques. However, the use of US and US-based intravenous agents extends far beyond imaging. In particular, there has been a surge in the fabrication of multimodality US contrast agents and theranostic US agents for cancer imaging and therapy.