scholarly journals Multiplexed Non-invasive in vivo Imaging to Assess Metabolism and Receptor Engagement in Tumor Xenografts

2019 ◽  
Author(s):  
Alena Rudkouskaya ◽  
Nattawut Sinsuebphon ◽  
Marien Ochoa ◽  
Joe E. Mazurkiewicz ◽  
Xavier Intes ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Metabolic Response ◽  
Imaging Modalities ◽  
Wide Field ◽  
Receptor Ligand ◽  
Non Invasive ◽  
Intracellular Drug Delivery

AbstractFollowing an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. To date, non-invasive quantitative imaging modalities that can comprehensively assess simultaneous cellular drug delivery efficacy and therapeutic response are lacking. In this regard, Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imaging offers a unique method to robustly quantify receptor-ligand engagement in vivo and subsequent intracellular internalization, which is critical to assess the delivery efficacy of targeted therapeutics. However, implementation of multiplexing optical imaging with FRET in vivo is challenging to achieve due to spectral crowding and cross-contamination. Herein, we report on a strategy that relies on a dark quencher that enables simultaneous assessment of receptor-ligand engagement and tumor metabolism in intact live mice. First, we establish that IRDye QC-1 (QC-1) is an effective NIR dark acceptor for the FRET-induced quenching of donor Alexa Fluor 700 (AF700) using in vitro NIR FLI microscopy and in vivo wide-field MFLI imaging. Second, we report on simultaneous in vivo imaging of the metabolic probe IRDye 800CW 2-deoxyglucose (2-DG) and MFLI-FRET imaging of NIR-labeled transferrin FRET pair (Tf-AF700/Tf-QC-1) uptake in tumors. Such multiplexed imaging revealed an inverse relationship between 2-DG uptake and Tf intracellular delivery, suggesting that 2-DG signal may predict the efficacy of intracellular targeted delivery. Overall, our methodology enables for the first time simultaneous non-invasive monitoring of intracellular drug delivery and metabolic response in preclinical studies.

scholarly journals Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 927
Author(s):  
Sebas D. Pronk ◽  
Erik Schooten ◽  
Jurgen Heinen ◽  
Esra Helfrich ◽  
Sabrina Oliveira ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Single Domain ◽  
Drug Conjugates ◽  
Intracellular Drug Delivery ◽  
Internalization Rate ◽  
Single Domain Antibodies ◽  
Different Characteristics

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.

Anti-HER2 VHH Targeted Fluorescent Liposome as Bimodal Nanoparticle for Drug Delivery and Optical Imaging

2021 ◽  
Vol 16 ◽  
Author(s):  
Sepideh Khaleghi ◽  
Fatemeh Rahbarizadeh ◽  
Shahryar Khoshtinat Nikkhoi
Keyword(s):  
Drug Delivery ◽  
Real Time ◽  
Targeted Delivery ◽  
Cell Tracking ◽  
Physicochemical Characterization ◽  
Target Cells ◽  
Wide Field ◽  
Cell Trafficking ◽  
Microscopy Imaging ◽  
Intracellular Drug Delivery

Objective: The aim of this study was to formulate fluorescent-labeled targeted immunoliposome to visualize the delivery and distribution of drugs in real-time. Methods: In this study, fluorescent-labeled liposomes were decorated with anti-HER2 VHH or Herceptin to improve the monitoring of intracellular drug delivery and tumor cell tracking with minimal side effects. The conjugation efficiency of antibodies was analyzed by SDS-PAGE silver staining. In addition, the physicochemical characterization of liposomes was performed using DLS and TEM. Finally, confocal microscopy visualized nanoparticles in the target cells. Results: Quantitative and qualitative methods characterized the intracellular uptake of 110±10 nm particles with near 70% conjugation efficiency. In addition, live-cell trafficking during hours of incubation was monitored by wide-field microscopy imaging. The results show that the fluorescent-labeled nanoparticles can specifically bind to HER2-positive breast cancer with minimal off-target delivery. Conclusion: This kind of nanoparticles can have several applications in personalized medicine, especially drug delivery and real-time visualization of cancer therapy. Moreover, this method also can be applied in the targeted delivery of contrast agents in imaging and thermotherapy.

scholarly journals Phthalocyanine incorporated alginate hydrogel with near infrared fluorescence for non-invasive imaging monitoring in vivo

RSC Advances ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. 6501-6510 ◽  
Author(s):  
Jie Liang ◽  
Xia Dong ◽  
Chang Wei ◽  
Deling Kong ◽  
Tianjun Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluorescence Imaging ◽  
Drug Delivery System ◽  
Delivery System ◽  
Near Infrared ◽  
Alginate Hydrogel ◽  
Near Infrared Fluorescence ◽  
Non Invasive ◽  
System P

A phthalocyanine incorporated alginate hydrogel with rhodamine was monitored by fluorescence imaging as a dual fluorescent drug delivery system.

In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles

2021 ◽  
Author(s):  
Tyler Nguyen ◽  
Jianhua Gao ◽  
Ping Wang ◽  
Abhignyan Nagesetti ◽  
Peter Andrews ◽  
...  
Keyword(s):  
Brain Stimulation ◽  
Targeted Delivery ◽  
Non Invasive

scholarly journals Mechanisms and Pharmaceutical Action of Lipid Nanoformulation of Natural Bioactive Compounds as Efficient Delivery Systems in the Therapy of Osteoarthritis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1108
Author(s):  
Oana Craciunescu ◽  
Madalina Icriverzi ◽  
Paula Ecaterina Florian ◽  
Anca Roseanu ◽  
Mihaela Trif
Keyword(s):  
Drug Delivery ◽  
Bioactive Compounds ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Joint Disease ◽  
Duration Of Action ◽  
Immune System Activation

Osteoarthritis (OA) is a degenerative joint disease. An objective of the nanomedicine and drug delivery systems field is to design suitable pharmaceutical nanocarriers with controllable properties for drug delivery and site-specific targeting, in order to achieve greater efficacy and minimal toxicity, compared to the conventional drugs. The aim of this review is to present recent data on natural bioactive compounds with anti-inflammatory properties and efficacy in the treatment of OA, their formulation in lipid nanostructured carriers, mainly liposomes, as controlled release systems and the possibility to be intra-articularly (IA) administered. The literature regarding glycosaminoglycans, proteins, polyphenols and their ability to modify the cell response and mechanisms of action in different models of inflammation are reviewed. The advantages and limits of using lipid nanoformulations as drug delivery systems in OA treatment and the suitable route of administration are also discussed. Liposomes containing glycosaminoglycans presented good biocompatibility, lack of immune system activation, targeted delivery of bioactive compounds to the site of action, protection and efficiency of the encapsulated material, and prolonged duration of action, being highly recommended as controlled delivery systems in OA therapy through IA administration. Lipid nanoformulations of polyphenols were tested both in vivo and in vitro models that mimic OA conditions after IA or other routes of administration, recommending their clinical application.

Near-infrared persistent luminescence hollow mesoporous nanospheres for drug delivery and in vivo renewable imaging

2016 ◽  
Vol 4 (48) ◽  
pp. 7845-7851 ◽  
Author(s):  
Junpeng Shi ◽  
Meng Sun ◽  
Xia Sun ◽  
Hongwu Zhang
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
High Sensitivity ◽  
Drug Carriers ◽  
Template Method ◽  
Persistent Luminescence ◽  
Deep Tissue ◽  
Large Capacity

Near-infrared persistent luminescence hollow mesoporous nanospheres have been synthesized via a template method. These nanospheres can be used as large capacity drug carriers and realize super long-term and high sensitivity tracking of drug delivery in deep tissue.

scholarly journals Non-invasive, real-time reporting drug release in vitro and in vivo

2015 ◽  
Vol 51 (32) ◽  
pp. 6948-6951 ◽  
Author(s):  
Yanfeng Zhang ◽  
Qian Yin ◽  
Jonathan Yen ◽  
Joanne Li ◽  
Hanze Ying ◽  
...  
Keyword(s):  
Drug Release ◽  
Real Time ◽  
Near Infrared ◽  
Reporting System ◽  
Real Time Monitoring ◽  
Near Infrared Fluorescence ◽  
Non Invasive ◽  
Fluorescence Dye

Anin vitroandin vivodrug-reporting system is developed for real-time monitoring of drug release via the analysis of the concurrently released near-infrared fluorescence dye.

scholarly journals Novel concept of the smart NIR-light–controlled drug release of black phosphorus nanostructure for cancer therapy

2018 ◽  
Vol 115 (3) ◽  
pp. 501-506 ◽  
Author(s):  
Meng Qiu ◽  
Dou Wang ◽  
Weiyuan Liang ◽  
Liping Liu ◽  
Yin Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Near Infrared ◽  
Black Phosphorus ◽  
Deep Penetration ◽  
Nir Light

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

scholarly journals Imaging of β-amyloid plaques by near infrared fluorescent tracers: a new frontier for chemical neuroscience

2015 ◽  
Vol 44 (7) ◽  
pp. 1807-1819 ◽  
Author(s):  
Matteo Staderini ◽  
María Antonia Martín ◽  
Maria Laura Bolognesi ◽  
J. Carlos Menéndez
Keyword(s):  
Near Infrared ◽  
Amyloid Plaques ◽  
Fluorescent Tracers ◽  
Non Invasive ◽  
Nir Imaging ◽  
New Frontier ◽  
Invasive Method ◽  
Β Amyloid

Near infrared (NIR) imaging is a promising and non-invasive method to visualize amyloid plaquesin vivo.

scholarly journals Niobium Carbide Loaded by Macrophage for Targeted Phototherapy Ablation of Breast Cancer

2020 ◽  
Author(s):  
Chiara Da Pieve ◽  
Gabriela Kramer Marek ◽  
Jolanta Saczko ◽  
Anant Shah ◽  
Florian Raes
Keyword(s):  
Animal Study ◽  
Human Body ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Niobium Carbide ◽  
Reactive Oxygen Species Generation ◽  
Large Animal Model ◽  
Large Animal ◽  
Photodynamic Effect

ABSTRACTAltough nanomaterial-mediated phototherapy has been extensively studied, the major antitumor success is limited to treating subcutaneous tumor on nude, lacking of clinically-relevant big animal study. Therefore, it is urgent to make further investigation on the typical big model, which is more closely related to the human body. In this work, niobium carbide (NbC) was selected as photoactive substance in virtue of its outstanding near infrared (NIR) absorption properties and resultantly NIR-triggered hyperthemia and reactive oxygen species generation for the synergetic photothermal and photodynamic effect. Moreover, macrophage was used as bio-carrier for the targeted delivery of NbC and the phagocytosis of macrophages was proved to be able to retain the photothermal/photodynamic effect of NbC. Resultantly, macrophage loaded NbC could realize complete removal of solid tumor on both of nude mice and big animal of rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) have been applied for monitoring the physiological evolutions of in vivo tumor post treatment, which clearly disclosed the photoablation process of tumor and provided a new way for the surveillance of tumor on the big animal study. Hence, large animal model study in this work presented higher clinical significance than the previous studies.SignificanceFindings show that niobium carbide carried by macrophages can be used for targeted phototherapy. At the same time, we applied the rabbit tumor model which is closer to the human body microenvironment.

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