Smart Triggered Release in Controlled Drug Delivery

Balaure, Paul Cătălin; Gudovan, Dragoş; Gudovan, Iulia Alexandra

doi:10.2174/1389450117666160401125034

Cited by 16 publications

(6 citation statements)

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“…Nanocarriers' surfaces can be modified with targeting ligands which are guided by specific ligand-receptor interactions, allowing precise spatial control of nanocarrier localization within the body [3]. Moreover, smart nano-transporters can be engineered to trigger drug release in response to small microenvironmental changes in local pH, temperature, redox potential, and enzyme activity, as well as to remote, externally applied stimuli such as electric fields, laser pulses, ultrasounds, and magnetic fields [3][4][5]. Furthermore, nanovehicles can overcome MDR mechanisms, including decreased uptake and increased efflux of tumor cell drugs [6].…”

Section: Introductionmentioning

confidence: 99%

Anti-Cancer Nanopowders and MAPLE-Fabricated Thin Films Based on SPIONs Surface Modified with Paclitaxel Loaded β-Cyclodextrin

et al. 2021

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Globally, cancer is the second most common cause of death, and Europe accounts for almost 25% of the global cancer burden, although its people make up only 10% of the world’s population. Conventional systemically administered anti-cancer drugs come with important drawbacks such as inefficiency due to poor bioavailability and improper biodistribution, severe side effects associated with low therapeutic indices, and the development of multidrug resistance. Therefore, smart nano-engineered targeted drug-delivery systems with tailored pharmacokinetics and biodistribution which can selectively deliver anti-cancer agents directly to the tumor site are the solution to most difficulties encountered with conventional therapeutic tools. Here, we report on the synthesis, physicochemical characterization, and in vitro evaluation of biocompatibility and anti-tumor activity of novel magnetically targetable SPIONs based on magnetite (Fe3O4) nanoparticles’ surface modified with β-cyclodextrin (CD) and paclitaxel (PTX)–guest–host inclusion complexes (Fe3O4@β-CD/PTX). Both pristine Fe3O4@β-CD nanopowders and PTX-loaded thin films fabricated by MAPLE technique were investigated. Pristine Fe3O4@β-CD and Fe3O4@β-CD/PTX thin films were physicochemically characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The biocompatibility of bare magnetic nanocomposite thin films was evaluated by MTT cell viability assay on a normal 3T3 osteoblast cell line culture and by measuring the level of NO in the culture medium. No significant modifications, neither in cell viability nor in NO level, could be observed, thereby demonstrating the excellent biocompatibility of the SPIONs thin films. Inverted phase-contrast microscopy showed no evident adverse effect on the morphology of normal osteoblasts. On the other hand, Fe3O4@β-CD/PTX films decreased the cell viability of the MG-63 osteosarcoma cell line by 85%, demonstrating excellent anti-tumor activity. The obtained results recommend these magnetic hybrid films as promising candidates for future delivery, and hyperthermia applications in cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Anti-Cancer Nanopowders and MAPLE-Fabricated Thin Films Based on SPIONs Surface Modified with Paclitaxel Loaded β-Cyclodextrin

et al. 2021

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“…The first generation of traditional liposomes was commonly formulated using phospholipids and cholesterol. The most recent generation of lipid vesicles also includes the use of (i) surface functionalization to reach the specific cell or tissue (targeted therapy), (ii) adjustable and adaptive structure to be administered via transdermal and/or oral routes (transfersome) and, (iii) external stimuli sensitive liposomes (electric and/or magnetic field, ultrasound, UV/light) or internal stimuli sensitive (pH, temperature, redox potential, enzymes, electrolyte concentration) to achieve a spatiotemporal control of drug release (smart delivery system) [ 155 , 156 , 157 ].…”

Section: Electroporationmentioning

confidence: 99%

Electroporation in Head-and-Neck Cancer: An Innovative Approach with Immunotherapy and Nanotechnology Combination

Pisani

Bertino

Prina-Mello

et al. 2022

Cancers

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Squamous cell carcinoma is the most common malignancy that arises in the head-and-neck district. Traditional treatment could be insufficient in case of recurrent and/or metastatic cancers; for this reason, more selective and enhanced treatments are in evaluation in preclinical and clinical trials to increase in situ concentration of chemotherapy drugs promoting a selectively antineoplastic activity. Among all cancer treatment types (i.e., surgery, chemotherapy, radiotherapy), electroporation (EP) has emerged as a safe, less invasive, and effective approach for cancer treatment. Reversible EP, using an intensive electric stimulus (i.e., 1000 V/cm) applied for a short time (i.e., 100 μs), determines a localized electric field that temporarily permealizes the tumor cell membranes while maintaining high cell viability, promoting cytoplasm cell uptake of antineoplastic agents such as bleomycin and cisplatin (electrochemotherapy), calcium (Ca2+ electroporation), siRNA and plasmid DNA (gene electroporation). The higher intracellular concentration of antineoplastic agents enhances the antineoplastic activity and promotes controlled tumor cell death (apoptosis). As secondary effects, localized EP (i) reduces the capillary blood flow in tumor tissue (“vascular lock”), lowering drug washout, and (ii) stimulates the immune system acting against cancer cells. After years of preclinical development, electrochemotherapy (ECT), in combination with bleomycin or cisplatin, is currently one of the most effective treatments used for cutaneous metastases and primary skin and mucosal cancers that are not amenable to surgery. To reach this clinical evidence, in vitro and in vivo models were preclinically developed for evaluating the efficacy and safety of ECT on different tumor cell lines and animal models to optimize dose and administration routes of drugs, duration, and intensity of the electric field. Improvements in reversible EP efficacy are under evaluation for HNSCC treatment, where the focus is on the development of a combination treatment between EP-enhanced nanotechnology and immunotherapy strategies.

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“…In recent years, the development of stimulus-triggered theranostic agents has attracted tremendous attention due to an integration of both disease imaging and targeted therapeutic effects. − These agents are commonly constructed by conjugating fluorescent dyes with drugs through a linker that responds to a disease-associated stimulus . Upon activation of a conditional stimulus like pH, enzyme, etc., the linker is cleaved, accompanied by fluorescence change due to variation of the electron structure of the dye, and the simultaneous targeted release of the corresponding drug with the enhancement of the drug’s efficacy and reduction of side effects. − Considering the importance of NO in AD pathology, we think it significant to explore a theranostic agent for AD, which is triggered by NO.…”

Section: Introductionmentioning

confidence: 99%

Rational Design of a Theranostic Agent Triggered by Endogenous Nitric Oxide in a Cellular Model of Alzheimer’s Disease

Wang

Zhang

et al. 2022

J. Med. Chem.

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Oxidative damage caused by upregulated nitric oxide (NO) plays an important role in the pathogenesis of Alzheimer's disease (AD). Currently, stimulus-triggered theranostic agents have received much attention due to benefits on disease imaging and targeted therapeutic effects. However, the development of a theranostic agent triggered by NO for AD remains unexplored. Herein, through the mechanism analysis of the reaction between a fluorophore of 9,14-diphenyl-9,14dihydrodibenzo[a,c]phenazine (DPAC) and NO, which we occasionally found and thereafter structure optimization of DPAC, a theranostic agent DPAC-(peg) 4 -memantine was fabricated. In an AD cellular model, DPAC-(peg) 4 -memantine exhibits NO sensing ability for AD imaging. Meanwhile, DPAC-(peg) 4 -memantine shows improved therapeutic by targeted drug release triggered by NO and sustained therapeutic effects owing to the synergetic antioxidative abilities via the anti-AD drug and NO scavenging. This work provides an unprecedented avenue for the studies on not only AD but also other diseases with NO upregulation.

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Smart Triggered Release in Controlled Drug Delivery

Cited by 16 publications

References 0 publications

Anti-Cancer Nanopowders and MAPLE-Fabricated Thin Films Based on SPIONs Surface Modified with Paclitaxel Loaded β-Cyclodextrin

Anti-Cancer Nanopowders and MAPLE-Fabricated Thin Films Based on SPIONs Surface Modified with Paclitaxel Loaded β-Cyclodextrin

Electroporation in Head-and-Neck Cancer: An Innovative Approach with Immunotherapy and Nanotechnology Combination

Rational Design of a Theranostic Agent Triggered by Endogenous Nitric Oxide in a Cellular Model of Alzheimer’s Disease

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