scholarly journals Real-time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-chip

Author(s):  
Natalia Feiner-Gracia ◽  
Adrianna Glinkowska Mares ◽  
Marina Buzhor ◽  
Romen Rodriguez-Trujillo ◽  
Josep Samitier ◽  
...  

ABSTRACTThe performance of supramolecular nanocarriers as drug delivery systems depends on their stability in the complex and dynamic biological media. After administration, nanocarriers are challenged by confronting different barriers such as shear stress and proteins present in blood, endothelial wall, extracellular matrix and eventually cancer cell membranes. While early disassembly will result in a premature drug release, extreme stability of the nanocarriers can lead to poor drug release and low efficiency. Therefore, comprehensive understanding of the stability and assembly state of supramolecular carriers in each stage of delivery is a key factor for the rational design of these systems. One of the key challenges is that current 2D in vitro models do not provide exhaustive information, as they do not fully recapitulate the 3D tumor microenvironment. This deficiency of the 2D models complexity is the main reason for the differences observed in vivo when testing the performance of supramolecular nanocarriers. Herein, we present a real-time monitoring study of self-assembled micelles stability and extravasation, combining spectral confocal microscopy and a microfluidic tumor-on-a-chip. The combination of advanced imaging and a reliable organ-on-a-chip model allow us to track micelle disassembly by following the spectral properties of the amphiphiles in space and time during the crucial steps of drug delivery. The spectrally active micelles were introduced under flow and their position and conformation followed during the crossing of barriers by spectral imaging, revealing the interplay between carrier structure, micellar stability and extravasation. Integrating the ability of the micelles to change their fluorescent properties when disassembled, spectral confocal imaging and 3D microfluidic tumor blood vessel-on-a-chip, resulted in the establishment of a robust testing platform, suitable for real-time imaging and evaluation of supramolecular drug delivery carrier’s stability.

2015 ◽  
Vol 51 (32) ◽  
pp. 6948-6951 ◽  
Author(s):  
Yanfeng Zhang ◽  
Qian Yin ◽  
Jonathan Yen ◽  
Joanne Li ◽  
Hanze Ying ◽  
...  

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.


2007 ◽  
Vol 25 (6) ◽  
pp. 1347-1354 ◽  
Author(s):  
Heiko Kranz ◽  
Erol Yilmaz ◽  
Gayle A. Brazeau ◽  
Roland Bodmeier

2021 ◽  
Author(s):  
Biswajit Roy ◽  
Rakesh Mengji ◽  
Samrat Roy ◽  
Bipul Pal ◽  
Avijit Jana ◽  
...  

In recent times, organelle-targeted drug delivery systems gained tremendous attention due to the site specific delivery of active drug molecules resulting in enhanced bioefficacy. In this context, the phototriggered drug delivery system (DDS) for releasing an active molecule is superior as it provides spatial and temporal control over the release. So far, near infrared (NIR) light responsive organelle targeted DDS has not yet been developed. Hence, we introduced a two-photon NIR-light responsive lysosome targeted ʽAIE + ESIPTʼ active single component DDS based on naphthalene chromophore. The Two-photon absorption cross-section of our DDS is 142 GM at 850 nm. The DDS was converted into pure organic nanoparticles for biological applications. Our nano-DDS is capable of selective targeting, AIE-luminogenic imaging, and drug release within the lysosome. In vitro studies using cancerous cell lines showed that our single component photoresponsive nanocarrier exhibited enhanced cytotoxicity and real-time monitoring ability of the drug release.


2021 ◽  
Vol 16 (7) ◽  
pp. 1029-1036
Author(s):  
Hongzhu Wang ◽  
Mengxun Chen ◽  
Liping Song ◽  
Youju Huang

A key challenge for nanoparticles-based drug delivery system is to achieve manageable drug release in tumour cell. In this study, a versatile system combining photothermal therapy and controllable drug release for tumour cells using temperature-sensitive block copolymer coupled Au NRs@SiO2 is reported. While the Au NRs serve as hyperthermal agent and the mesoporous silica was used to improve the drug loading and decrease biotoxicity. The block copolymer acted as “gatekeeper” to regulate the release of model drug (Doxorubicin hydrochloride, DOX). Through in vivo and in vitro experiments, we achieved the truly controllable drug release and photothermal therapy with the collaborative effect of the three constituents of the nanocomposites. The reported nanocomposites pave the way to high-performance controllable drug release and photothermal therapy system.


2018 ◽  
Vol 15 (144) ◽  
pp. 20180236 ◽  
Author(s):  
Alessandra Marrella ◽  
Michele Iafisco ◽  
Alessio Adamiano ◽  
Stefano Rossi ◽  
Maurizio Aiello ◽  
...  

Alternative drug delivery approaches to treat cardiovascular diseases are currently under intense investigation. In this domain, the possibility to target the heart and tailor the amount of drug dose by using a combination of magnetic nanoparticles (NPs) and electromagnetic devices is a fascinating approach. Here, an electromagnetic device based on Helmholtz coils was generated for the application of low-frequency magnetic stimulations to manage drug release from biocompatible superparamagnetic Fe-hydroxyapatite NPs (FeHAs). Integrated with a fluidic circuit mimicking the flow of the cardiovascular environment, the device was efficient to trigger the release of a model drug (ibuprofen) from FeHAs as a function of the applied frequencies. Furthermore, the biological effects on the cardiac system of the identified electromagnetic exposure were assessed in vitro and in vivo by acute stimulation of isolated adult cardiomyocytes and in an animal model. The cardio-compatibility of FeHAs was also assessed in vitro and in an animal model. No alterations of cardiac electrophysiological properties were observed in both cases, providing the evidence that the combination of low-frequency magnetic stimulations and FeHAs might represent a promising strategy for controlled drug delivery to the failing heart.


Talanta ◽  
2012 ◽  
Vol 88 ◽  
pp. 631-637 ◽  
Author(s):  
Mira Kim ◽  
Ji Hye Seo ◽  
Won Il Jeon ◽  
Mi-Yeon Kim ◽  
Keunchang Cho ◽  
...  

2005 ◽  
Vol 04 (05n06) ◽  
pp. 855-861 ◽  
Author(s):  
MARTIN GARNETT

The use of nanosized materials changes the way in which drugs are handled by the body and offers opportunities to improve drug delivery. The physiological mechanisms controlling the distribution of nanosized materials (enhanced permeability and retention effect, cellular uptake pathways and opsonisation/elimination of nanoparticles) are described. Two different nanosized drug delivery systems are considered; drug delivery and DNA delivery. The deficiencies of currently available biodegradable polymers for preparation of drug containing nanoparticles are mainly the amount of drug that can be incorporated and the rapid rate of drug release. The development of new biodegradable polymers which can interact with the drug and so significantly increase drug loading and decrease the rate of drug release are outlined. DNA delivery necessitates overcoming a variety of biological barriers. We are developing polyelectrolyte complexes of DNA with cationic polyamidoamines (PAA) as a delivery system. Complexing PAA with DNA results in good transfection of cells in vitro. However, in vivo, a more complex arrangement of PAA, Polyethylene glycol-PAA copolymers, DNA and the use of ligands will be required. Despite these efforts, further developments will be needed in nanotechnology for both drug and DNA nanoparticle delivery systems to achieve our clinical objectives.


2018 ◽  
Author(s):  
Mahendran Subramanian ◽  
Arkadiusz Miaskowski ◽  
Ajit K. Mahapatro ◽  
Ondrej Hovorka ◽  
Jon Dobson

AbstractHeat dissipation during magnetization reversal processes in magnetic nanoparticles (MNP), upon exposure to alternating magnetic fields (AMF), has been extensively studied in relation to applications in magnetic fluid hyperthermia (MFH). This current paper demonstrates the design, fabrication, and evaluation of an efficient instrument, operating on this principle, for use as (i) a non-contact, in vitro, real-time temperature monitor; (ii) a drug release analysis system (DRAS); (iii) a high flux density module for AMF-mediated MNP studies; and (iv) an in vivo coil setup for real-time, whole body thermal imaging. The proposed DRAS is demonstrated by an AMF-mediated drug release proof-of-principle experiment. Also, the technique described facilitates non-contact temperature measurements of specific absorption rate (SAR) as accurately as temperature measurements using a probe in contact with the sample. Numerical calculations estimating the absolute and root mean squared flux densities, and other MNP – AMF studies suggest that the proposed stacked planar coil module could be employed for calorimetry. Even though the proposed in vivo coil setup could be used for real-time, whole body thermal imaging (within the limitations due to issues of penetration depth), further design effort is required in order to enhance the energy transfer efficiency.


2020 ◽  
Author(s):  
Xingyu He ◽  
Zheng Yuan ◽  
Samantha Gaeke ◽  
Winston W.-Y. Kao ◽  
S. Kevin Li ◽  
...  

AbstractThe current standard of care for posterior segment eye diseases, such as age-related macular degeneration and diabetic macular edema, is frequent intravitreal injections or sustained-release drug implants. Drug implants have side effects due to the burst release of the drugs, and their release cannot be easily controlled after implantation. Present study attempts to develop a dosage-controllable drug delivery implant which consists of a nanoporous biodegradable PLGA capsule and light-activated liposomes. Controllable drug release from the implant was achieved by using pulsed near-infrared (NIR) laser both in vitro and in vivo. The in vitro drug release kinetics from two different initial dose implants, 1000 μg and 500 μg, was analyzed by fitting zero order and first order kinetics, as well as the Korsmeyer-Peppas and Higuchi models. The 1000 μg and 500 μg implants fit the first-order and zero-order kinetics model, respectively, the best. The multiple drug releases in the vitreous was determined by in vivo fluorimeter, which was consistent with the in vitro data. The dose released was also clinically relevant. Histology and optical and ultrasound imaging data showed no abnormality in the eyes received implant treatment suggesting that the drug delivery system was safe to the retina. This on-demand dose-controllable drug delivery system could be potentially used for long-term posterior eye disease treatment.


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