Sialic acid–targeted drug delivery and imaging system for pH- and glutathione-triggered multiple anticancer drug release and enhanced oxidative stress

2020 ◽  
Vol 35 (3) ◽  
pp. 254-269
Author(s):  
Licong Peng ◽  
Xianwu Zeng ◽  
Qianqian Qi ◽  
Hailiang Zhang ◽  
Jinping Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Delivery ◽  
Quantum Dots ◽  
Photodynamic Therapy ◽  
Sialic Acid ◽  
Multiple Drug ◽  
Emission Computed Tomography ◽  
Light Conditions ◽  
Multiple Drug Delivery

The emergence of multiple drug delivery systems can solve the disadvantages of single-drug therapy, such as high dose and easy generation of drug resistance. Here, we designed a sialic acid–targeted dextran-mercaptopurine prodrug linked by carbonyl vinyl sulfide for coordinate ZnO quantum dots to achieve multiple drug delivery (doxorubicin, 5-fluorouracil, 6-mercaptopurine), which can be released under the trigger of pH and glutathione. To enhance the antitumor effect, we used inorganic photosensitizer CdSe quantum dots to achieve photodynamic therapy, which can produce cytotoxic reactive oxygen species (hydroxyl radicals) under light conditions. Notably, we found that glutathione is consumed by the delivery of 6-mercaptopurine. It is able to efficiently amplify intracellular oxidative stress via increasing •OH generation. After chelating 99mTc4+ radioisotopes by diethylenetriamine pentaacetic acid, the drug delivery system could be tracked under in vivo single-photon emission computed tomography imaging. The results showed that the phenylboronic acid targeting substance can specifically recognize sialic acid, so that the drug system has a good accumulation in the tumor site, which can better increase the therapeutic effect. Compared to free doxorubicin, the drug system can reduce the IC50 value of cells 4.4-fold under light conditions and significantly inhibit tumor growth in vivo. These data indicate that the sialic acid–targeted nanomedicine system has achieved ideal antitumor effects and apparent photodynamic therapy effects and has broad application prospects.

scholarly journals Degradation of Drug Delivery Nanocarriers and Payload Release: A Review of Physical Methods for Tracing Nanocarrier Biological Fate

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 770
Author(s):  
Patrick M. Perrigue ◽  
Richard A. Murray ◽  
Angelika Mielcarek ◽  
Agata Henschke ◽  
Sergio E. Moya
Keyword(s):  
Drug Delivery ◽  
Laser Scanning ◽  
Single Photon ◽  
Photon Emission ◽  
Correlation Spectroscopy ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Emission Computed Tomography ◽  
Systemic Delivery

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.

scholarly journals Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action

2021 ◽  
Vol 22 (15) ◽  
pp. 8106
Author(s):  
Tianming Song ◽  
Yawei Qu ◽  
Zhe Ren ◽  
Shuang Yu ◽  
Mingjian Sun ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Photodynamic Therapy ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Potential Applications ◽  
Zno Quantum Dots ◽  
Zno Qds

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

Multiple drug delivery hydrogel system for spinal cord injury repair strategies

2012 ◽  
Vol 159 (2) ◽  
pp. 271-280 ◽  
Author(s):  
Giuseppe Perale ◽  
Filippo Rossi ◽  
Marco Santoro ◽  
Marco Peviani ◽  
Simonetta Papa ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Multiple Drug ◽  
Injury Repair ◽  
Cord Injury ◽  
Multiple Drug Delivery ◽  
Hydrogel System

Application of Hydrogel Biocomposites for Multiple Drug Delivery

2017 ◽  
pp. 139-165 ◽  
Author(s):  
S.J. Owonubi ◽  
S.C. Agwuncha ◽  
E. Mukwevho ◽  
B.A. Aderibigbe ◽  
E.R. Sadiku ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Multiple Drug ◽  
Multiple Drug Delivery

A smart drug-delivery nanosystem based on carboxylated graphene quantum dots for tumor-targeted chemotherapy

Nanomedicine ◽  
2019 ◽  
Vol 14 (15) ◽  
pp. 2011-2025 ◽  
Author(s):  
Zhen Li ◽  
Jialong Fan ◽  
Chunyi Tong ◽  
Hongyan Zhou ◽  
Wenmiao Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Quantum Dots ◽  
Folic Acid ◽  
Ethylene Glycol ◽  
Drug Delivery System ◽  
Delivery System ◽  
Graphene Quantum Dots ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene

Aim: Constructing a new drug-delivery system using carboxylated graphene quantum dots (cGQDs) for tumor chemotherapy in vivo. Materials & methods: A drug-delivery system was synthesized through a crosslink reaction of cGQDs, NH2-poly(ethylene glycol)-NH2 and folic acid. Results: A drug delivery system of folic acid-poly(ethylene glycol)-cGQDs was successfully constructed with ideal entrapment efficiency (97.5%) and drug-loading capacity (40.1%). Cell image indicated that the nanosystem entered into human cervical cancer cells mainly through macropinocytosis-dependent pathway. In vivo experiments showed the outstanding antitumor ability and low systemic toxicity of this nanodrug-delivery system. Conclusion: The newly developed drug-delivery system provides an important alternative for tumor therapy without causing systemic adverse effects.

scholarly journals Internalization of targeted quantum dots by brain capillary endothelial cells in vivo

2015 ◽  
Vol 36 (4) ◽  
pp. 731-742 ◽  
Author(s):  
Sarah Paris-Robidas ◽  
Danny Brouard ◽  
Vincent Emond ◽  
Martin Parent ◽  
Frédéric Calon
Keyword(s):  
Drug Delivery ◽  
Quantum Dots ◽  
Endothelial Cells ◽  
Transferrin Receptor ◽  
Volume Of Distribution ◽  
Electron Microscopic ◽  
Brain Capillary ◽  
Brain Capillary Endothelial Cells ◽  
Capillary Endothelial Cells

Receptors located on brain capillary endothelial cells forming the blood–brain barrier are the target of most brain drug delivery approaches. Yet, direct subcellular evidence of vectorized transport of nanoformulations into the brain is lacking. To resolve this question, quantum dots were conjugated to monoclonal antibodies (Ri7) targeting the murine transferrin receptor. Specific transferrin receptor-mediated endocytosis of Ri7-quantum dots was first confirmed in N2A and bEnd5 cells. After intravenous injection in mice, Ri7-quantum dots exhibited a fourfold higher volume of distribution in brain tissues, compared to controls. Immunofluorescence analysis showed that Ri7-quantum dots were sequestered throughout the cerebral vasculature 30 min, 1 h, and 4 h post injection, with a decline of signal intensity after 24 h. Transmission electron microscopic studies confirmed that Ri7-quantum dots were massively internalized by brain capillary endothelial cells, averaging 37 ± 4 Ri7-quantum dots/cell 1 h after injection. Most quantum dots within brain capillary endothelial cells were observed in small vesicles (58%), with a smaller proportion detected in tubular structures or in multivesicular bodies. Parenchymal penetration of Ri7-quantum dots was extremely low and comparable to control IgG. Our results show that systemically administered Ri7-quantum dots complexes undergo extensive endocytosis by brain capillary endothelial cells and open the door for novel therapeutic approaches based on brain endothelial cell drug delivery.

scholarly journals Use of Cyclodextrins in Anticancer Photodynamic Therapy Treatment

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1936 ◽  
Author(s):  
Amina Ben Mihoub ◽  
Ludivine Larue ◽  
Albert Moussaron ◽  
Zahraa Youssef ◽  
Ludovic Colombeau ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Molecular Oxygen ◽  
Inclusion Complexes ◽  
Water Solubility ◽  
Cellular Damage ◽  
Hybrid Nanoparticles ◽  
Binding Modes

Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CD–PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies, (2) incorporating CD–PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs.

scholarly journals Core-shell Semiconductor Nanocrystals: Effect of Composition, Size, Surface Coatings on their Optical Properties, Toxicity and Pharmacokinetics

2017 ◽  
Vol 23 (3) ◽  
pp. 340-349 ◽  
Author(s):  
Wafa' T. Al-Jamal
Keyword(s):  
Quantum Dots ◽  
Optical Properties ◽  
Photodynamic Therapy ◽  
Biomedical Applications ◽  
Semiconductor Nanocrystals ◽  
Organic Dye ◽  
Surface Coatings ◽  
Core Shell ◽  
Biomedical Field

Quantum dots are semiconducting nanocrystals that exhibit extraordinary optical properties. QD have shown higher photostability compared to standard organic dye type probes. Therefore, they have been heavily explored in the biomedical field. This review will discuss the different approaches to synthesis, solubilise and functionalise QD. Their main biomedical applications in imaging and photodynamic therapy will be highlighted. Finally, QD biodistribution profile and in vivo toxicity will be discussed.

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