A real-time technique for selective molecular imaging and drug delivery in large blood vessels

Melanoma is an aggressive form of skin cancer with a very high mortality rate. Early diagnosis of the disease, the utilization of more potent pharmacological agents, and more effective drug delivery systems are essential to achieve an optimal treatment plan. The applications of nanotechnology to improve therapeutic efficacy and early diagnosis for melanoma treatment have received great interest among researchers and clinicians. In this review, we summarize the recent progress of utilizing various nanomaterials for theranostics of melanoma. The key importance of using nanomaterials for theranostics of melanoma is to improve efficacy and reduce side effects, ensuring safe implementation in clinical use. As opposed to conventional in vitro diagnostic methods, in vivo medical imaging technologies have the advantages of being a type of non-invasive, real-time monitoring. Several common nanoparticles, including ultrasmall superparamagnetic iron oxide nanoparticles, silica nanoparticles, and carbon-based nanoparticles, have been applied to deliver chemotherapeutic agents for the theranostics of melanoma. The application of nanomaterials for theranostics in molecular imaging (MRI, PET, US, OI, etc.) plays an important role in targeting drug delivery of melanoma, by monitoring the distribution site of the molecular imaging probe and the therapeutic drug in the body in real-time. Hence, it is worthwhile to anticipate the approval of these nanomaterials for theranostics in molecular imaging by the US Food and Drug Administration in clinical trials.

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Real-time quantitative monitoring of in vitro nasal drug delivery by a nasal epithelial mucosa-on-a-chip model

Expert Opinion on Drug Delivery ◽

10.1080/17425247.2021.1873274 ◽

2021 ◽

Author(s):

Hanieh Gholizadeh ◽

Hui Xin Ong ◽

Peta Bradbury ◽

Agisilaos Kourmatzis ◽

Daniela Traini ◽

...

Keyword(s):

Drug Delivery ◽

Real Time ◽

Nasal Drug Delivery ◽

Quantitative Monitoring

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Multi-Modal Multi-Spectral Intravital Microscopic Imaging of Signaling Dynamics in Real-Time during Tumor–Immune Interactions

Cells ◽

10.3390/cells10030499 ◽

2021 ◽

Vol 10 (3) ◽

pp. 499

Author(s):

Tracy W. Liu ◽

Seth T. Gammon ◽

David Piwnica-Worms

Keyword(s):

Molecular Imaging ◽

Single Cell ◽

Real Time ◽

Bioluminescence Imaging ◽

Emission Spectra ◽

Ccd Camera ◽

Microscopic Imaging ◽

Signaling Dynamics ◽

Window Chamber

Intravital microscopic imaging (IVM) allows for the study of interactions between immune cells and tumor cells in a dynamic, physiologically relevant system in vivo. Current IVM strategies primarily use fluorescence imaging; however, with the advances in bioluminescence imaging and the development of new bioluminescent reporters with expanded emission spectra, the applications for bioluminescence are extending to single cell imaging. Herein, we describe a molecular imaging window chamber platform that uniquely combines both bioluminescent and fluorescent genetically encoded reporters, as well as exogenous reporters, providing a powerful multi-plex strategy to study molecular and cellular processes in real-time in intact living systems at single cell resolution all in one system. We demonstrate that our molecular imaging window chamber platform is capable of imaging signaling dynamics in real-time at cellular resolution during tumor progression. Importantly, we expand the utility of IVM by modifying an off-the-shelf commercial system with the addition of bioluminescence imaging achieved by the addition of a CCD camera and demonstrate high quality imaging within the reaches of any biology laboratory.

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PATH-04. THE BLOOD-BRAIN BARRIER IN DIFFUSE MIDLINE GLIOMA AND ITS IMPLICATIONS FOR DRUG DELIVERY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.686 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii164-ii164

Author(s):

Rianne Haumann ◽

Fatma El-Khouly ◽

Marjolein Breur ◽

Sophie Veldhuijzen van Zanten ◽

Gertjan Kaspers ◽

...

Keyword(s):

Drug Delivery ◽

Blood Vessels ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Vascular Density ◽

Zonula Occludens ◽

Blood Brain ◽

Zonula Occludens 1 ◽

End Stage ◽

Diffuse Midline Glioma

Abstract INTRODUCTION Chemotherapy has been unsuccessful for pediatric diffuse midline glioma (DMG) most likely due to an intact blood-brain barrier (BBB). However, the BBB has not been characterized in DMG and therefore its implications for drug delivery are unknown. In this study we characterized the BBB in DMG patients and compared this to healthy controls. METHODS End-stage DMG pontine samples (n=5) were obtained from the VUmc diffuse intrinsic pontine glioma (DIPG) autopsy study and age-matched healthy pontine samples (n=22) were obtained from the NIH NeuroBioBank. Tissues were stained for BBB markers claudin-5, zonula occludens-1, laminin, and PDGFRβ. Claudin-5 stains were used to determine vascular density and diameter. RESULTS In DMG, expression of claudin-5 was reduced and dislocated to the abluminal side of endothelial cells. In addition, the expression of zonula occludens-1 was reduced. The basement membrane protein laminin expression was reduced at the glia limitans in both pre-existent vessels and neovascular proliferation. PDGFRβ expression was not observed in DMG but was present in healthy pons. Furthermore, the number of blood vessels in DMG was significantly (P< 0.01) reduced (13.9 ± 11.8/mm2) compared to healthy pons (26.3 ± 14.2/mm2). Markedly, the number of small blood vessels (< 10µm) was significantly lower (P< 0.01) while larger blood vessels (> 10µm) were not significantly different (P= 0.223). The mean vascular diameter was larger for DMG 9.3 ± 9.9µm compared to 7.7 ± 9.0µm for healthy pons (P= 0.016). CONCLUSION Both the BBB and the vasculature are altered at end-stage DMG. The reduced vascular density might have implications for several drug delivery methods such as focused ultrasound and convection enhanced delivery that are being explored for the treatment of DMG. The functional effects of the structurally altered BBB remain unknown and further research is needed to evaluate the BBB integrity at end-stage DMG

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Multifunctional Nanoprobe for the Delivery of Therapeutic siRNA and Real-Time Molecular Imaging of Parkinson’s Disease Biomarkers

ACS Applied Materials & Interfaces ◽

10.1021/acsami.0c22112 ◽

2021 ◽

Author(s):

Rui Li ◽

Yi Li ◽

Mingdao Mu ◽

Boguang Yang ◽

Xiaoyu Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Molecular Imaging ◽

Real Time ◽

Disease Biomarkers ◽

Multifunctional Nanoprobe

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A Magnetically Guided Self‐Rolled Microrobot for Targeted Drug Delivery, Real‐Time X‐Ray Imaging, and Microrobot Retrieval

Advanced Healthcare Materials ◽

10.1002/adhm.202001681 ◽

2021 ◽

pp. 2001681

Author(s):

Kim Tien Nguyen ◽

Gwangjun Go ◽

Zhen Jin ◽

Bobby Aditya Darmawan ◽

Ami Yoo ◽

...

Keyword(s):

Drug Delivery ◽

Real Time ◽

Targeted Drug Delivery ◽

X Ray ◽

X Ray Imaging ◽

Targeted Drug

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The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles

Pharmaceutics ◽

10.3390/pharmaceutics13010119 ◽

2021 ◽

Vol 13 (1) ◽

pp. 119

Author(s):

Simone A.G. Langeveld ◽

Inés Beekers ◽

Gonzalo Collado-Lara ◽

Antonius F. W. van der Steen ◽

Nico de Jong ◽

...

Keyword(s):

Drug Delivery ◽

Molecular Imaging ◽

High Speed ◽

Phase Distribution ◽

Direct Method ◽

Ultrasound Contrast Agents ◽

Lipid Phase ◽

Acoustic Behavior ◽

Ultrasound Molecular Imaging ◽

The Impact

Phospholipid-coated microbubbles are ultrasound contrast agents that can be employed for ultrasound molecular imaging and drug delivery. For safe and effective implementation, microbubbles must respond uniformly and predictably to ultrasound. Therefore, we investigated how lipid handling and phase distribution affected the variability in the acoustic behavior of microbubbles. Cholesterol was used to modify the lateral molecular packing of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based microbubbles. To assess the effect of lipid handling, microbubbles were produced by a direct method, i.e., lipids directly dispersed in an aqueous medium or indirect method, i.e., lipids first dissolved in an organic solvent. The lipid phase and ligand distribution in the microbubble coating were investigated using confocal microscopy, and the acoustic response was recorded with the Brandaris 128 ultra-high-speed camera. In microbubbles with 12 mol% cholesterol, the lipids were miscible and all in the same phase, which resulted in more buckle formation, lower shell elasticity and higher shell viscosity. Indirect DSPC microbubbles had a more uniform response to ultrasound than direct DSPC and indirect DSPC-cholesterol microbubbles. The difference in lipid handling between direct and indirect DSPC microbubbles significantly affected the acoustic behavior. Indirect DSPC microbubbles are the most promising candidate for ultrasound molecular imaging and drug delivery applications.

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