scholarly journals Folic Acid-Decorated β-Cyclodextrin-Based Poly(ε-caprolactone)-dextran Star Polymer with Disulfide Bond-Linker as Theranostic Nanoparticle for Tumor-Targeted MRI and Chemotherapy

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 52
Author(s):  
Huikang Yang ◽  
Nianhua Wang ◽  
Ruimeng Yang ◽  
Liming Zhang ◽  
Xinqing Jiang
Keyword(s):  
Folic Acid ◽  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Polymeric Nanoparticles ◽  
Folate Receptor ◽  
Superparamagnetic Iron Oxide ◽  
Star Polymer ◽  
Theranostic Nanoparticles ◽  
Targeted Mri

β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

scholarly journals Folic Acid Decorated β-Cyclodextrin-Based Poly(ε-Caprolactone)/Dextran Star Polymer with Disulfide Bond-Linker as Theranostic Nanoparticle for Tumor-Targeted MRI and Chemotherapy

2021 ◽  
Author(s):  
Huikang Yang ◽  
Nianhua Wang ◽  
Ruimeng Yang ◽  
Li-Ming Zhang ◽  
Xinqing Jiang
Keyword(s):  
Folic Acid ◽  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Folate Receptor ◽  
Superparamagnetic Iron Oxide ◽  
Star Polymer ◽  
Iron Oxide Particles ◽  
Theranostic Nanoparticles ◽  
Targeted Mri

β-cyclodextrin-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, we synthesized well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) acted as theranostic nanoparticles for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX) and superparamagnetic iron oxide particles (SPIO) were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to folate receptor-mediated endocytosis process of the nanoparticles and GSH triggered disulfide-bonds cleaving.Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO showed strong MRI contrast enhancement properties. In conclusion, folate-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

Folic Acid Functionalized Chlorin e6-Superparamagnetic Iron Oxide Nanocarriers as a Theranostic Agent for MRI-Guided Photodynamic Therapy

2021 ◽  
Vol 17 (2) ◽  
pp. 205-215
Author(s):  
Zhenbo Sun ◽  
Mingfang Luo ◽  
Jia Li ◽  
Ailing Wang ◽  
Xucheng Sun ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Folic Acid ◽  
Iron Oxide ◽  
Near Infrared ◽  
Biological Fluids ◽  
Superparamagnetic Iron Oxide ◽  
Chlorin E6 ◽  
Theranostic Agent

Imaging-guided cancer theranostic is a promising strategy for cancer diagnostic and therapeutic. Photodynamic therapy (PDT), as an approved treatment modality, is limited by the poor solubility and dispersion of photosensitizers (PS) in biological fluids. Herein, it is demonstrated that superparamagnetic iron oxide (SPIO)-based nanoparticles (SCFs), prepared by conjugated with Chlorin e6 (Ce6) and modified with folic acid (FA) on the surface, can be used as versatile drug delivery vehicles for effective PDT. The nanoparticles are great carriers for photosensitizer Ce6 with an extremely high loading efficiency. In vitro fluorescence imaging and in vivo magnetic resonance imaging (MRI) results indicated that SCFs selectively accumulated in tumor cells. Under near-infrared laser irradiation, SCFs were confirmed to be capable of inducing low cell viability of RM-1 cells In vitro and displaying efficient tumor ablation with negligible side effects in tumor-bearing mice models.

scholarly journals Evaluating biological activity of folic acid-modified and 10-hydroxycamptothecin-loaded mesoporous silica nanoparticles

2021 ◽  
Author(s):  
Mei-Xia Zhao ◽  
Di-Feng Chen ◽  
Xue-Jie Zhao ◽  
Lin-Song Li ◽  
Yong-Fang Liu
Keyword(s):  
Folic Acid ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Folate Receptor ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carriers ◽  
Transmission Electron ◽  
Before And After ◽  
Drug Efficiency

Targeted nanocarrier can selectively deliver anti-tumor drugs to cancer sites improving drug efficiency. Accordingly, a targeted nanocarrier (MSN-FA) was synthesized based on folic acid (FA) modified mesoporous silica nanoparticles (MSNs). These loaded with 10-hydroxycamptothecin (HCPT) to obtain the nano-drug MSN-FA@HCPT. These nanocarriers were characterized by transmission electron microscopy (TEM), zeta potential, ultraviolet-visible spectroscopy (UV-Vis), fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). Notably, the nanocarriers were nearly spherical before and after loading HCPT and exhibited good dispersibility. Also, folate receptor (FR) over-expressing HeLa cells and FR deficient HepG2 cells were used to evaluate in vitro cellular uptake and cytotoxicity of MSN-FA@HCPT and MSN@HCPT. Interestingly, FA-modified nanocarriers enhanced the cytotoxicity of HCPT by improving drug targeting to tumor cells. Also, apoptotic and mitochondrial membrane potential (MMP) reducing effects of MSN-FA@HCPT were more prominent than the MSNs without FA modification. MSN-FA@HCPT can be excellent drug carriers with profound biomedical applications.

scholarly journals Disulfide Bond Formation at the C Termini of Vaccinia Virus A26 and A27 Proteins Does Not Require Viral Redox Enzymes and Suppresses Glycosaminoglycan-Mediated Cell Fusion

2009 ◽  
Vol 83 (13) ◽  
pp. 6464-6476 ◽  
Author(s):  
Yao-Cheng Ching ◽  
Che-Sheng Chung ◽  
Cheng-Yen Huang ◽  
Yu Hsia ◽  
Yin-Liang Tang ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Cell Fusion ◽  
Disulfide Bond ◽  
Protein Complex ◽  
Disulfide Bonds ◽  
Bond Formation ◽  
In Vitro Mutagenesis ◽  
Disulfide Bond Formation ◽  
Infected Cells

ABSTRACT Vaccinia virus A26 protein is an envelope protein of the intracellular mature virus (IMV) of vaccinia virus. A mutant A26 protein with a truncation of the 74 C-terminal amino acids was expressed in infected cells but failed to be incorporated into IMV (W. L. Chiu, C. L. Lin, M. H. Yang, D. L. Tzou, and W. Chang, J. Virol 81:2149-2157, 2007). Here, we demonstrate that A27 protein formed a protein complex with the full-length form but not with the truncated form of A26 protein in infected cells as well as in IMV. The formation of the A26-A27 protein complex occurred prior to virion assembly and did not require another A27-binding protein, A17 protein, in the infected cells. A26 protein contains six cysteine residues, and in vitro mutagenesis showed that Cys441 and Cys442 mediated intermolecular disulfide bonds with Cys71 and Cys72 of viral A27 protein, whereas Cys43 and Cys342 mediated intramolecular disulfide bonds. A26 and A27 proteins formed disulfide-linked complexes in transfected 293T cells, showing that the intermolecular disulfide bond formation did not depend on viral redox pathways. Finally, using cell fusion from within and fusion from without, we demonstrate that cell surface glycosaminoglycan is important for virus-cell fusion and that A26 protein, by forming complexes with A27 protein, partially suppresses fusion.

The kinetics of in vitro reoxidation and reduction of the inter heavy–light chain disulfide bond in an unusual murine immunoglobulin G myeloma protein lacking inter-heavy chain disulfide bonds

1979 ◽  
Vol 57 (3) ◽  
pp. 279-285 ◽  
Author(s):  
Maire E. Percy ◽  
Lebe Chang ◽  
Catherine Demoliou ◽  
Reuben Baumal
Keyword(s):  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Peptide Mapping ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Sedimentation Coefficient ◽  
Disulfide Bridge ◽  
Myeloma Protein ◽  
Kinetics Of

After 5 years of subcutaneous transfer in Balb/C mice, our MOPC 173 myeloma tumour line (originally an IgG2a,κ H2L2-producer) exclusively synthesized an unusual IgG2b,κ protein lacking inter-heavy (H) chain disulfide bonds. This protein was designated MOPC 173B. On sodium dodecyl sulfate – polyacrylamide gel electrophoresis, it migrated with an apparent molecular weight of 77 000; following complete reduction and alkylation, the mobilities of its constituent H and light (L) chains were found to differ slightly from those of MOPC 173 H2L2. MOPC 173B was serologically identical to another typical IgG2b,κ myeloma protein, MOPC 195, and peptide mapping studies showed that it possessed only the inter H–L disulfide bond characteristic of typical IgG2b,κ proteins. In a nondissociating solvent, the sedimentation coefficient of the protein was 6.3S even at concentrations as low as 0.2 mg/ml, indicating that noncovalent interactions existed between two half-molecule subunits. Since this unusual IgG myeloma protein contained only a single category of interchain disulfide bridge, the inter H–L bond, it was an ideal model system for characterization of the kinetics of formation and reduction of interchain disulfide bonds. The kinetics of the glutathione-catalyzed reoxidation of the inter H–L disulfide bridge in MOPC 173B followed an apparent second-order rate equation. In contrast, reduction of its inter H–L bridge under anaerobic conditions with dithioerythritol in excess, was strictly a first-order process and not a simple reversal of the reoxidation. These studies provide the basis for the more complex mathematical models that describe the reoxidation and reduction of typical immunoglobulin molecules.

scholarly journals Optimisation of Folate-Mediated Liposomal Encapsulated Arsenic Trioxide for Treating HPV-Positive Cervical Cancer Cells In Vitro

2019 ◽  
Vol 20 (9) ◽  
pp. 2156 ◽  
Author(s):  
Akhtar ◽  
Ghali ◽  
Wang ◽  
Bell ◽  
Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Folic Acid ◽  
Cancer Cells ◽  
Arsenic Trioxide ◽  
Folate Receptor ◽  
Hpv Infection ◽  
Cytotoxicity Studies ◽  
Cervical Cancer Cells ◽  
Infected Cells

High-risk human papilloma virus (HPV) infection is directly associated with cervical cancer development. Arsenic trioxide (ATO), despite inducing apoptosis in HPV-infected cervical cancer cells in vitro, has been compromised by toxicity and poor pharmacokinetics in clinical trials. Therefore, to improve ATO’s therapeutic profile for HPV-related cancers, this study aims to explore the effects of length of ligand spacers of folate-targeted liposomes on the efficiency of ATO delivery to HPV-infected cells. Fluorescent ATO encapsulated liposomes with folic acid (FA) conjugated to two different PEG lengths (2000 Da and 5000 Da) were synthesised, and their cellular uptake was examined for HPV-positive HeLa and KB and HPV-negative HT-3 cells using confocal microscopy, flow cytometry, and spectrophotometer readings. Cellular arsenic quantification and anti-tumour efficacy was evaluated through inductively coupled plasma-mass spectrometry (ICP-MS) and cytotoxicity studies, respectively. Results showed that liposomes with a longer folic acid-polyethylene glycol (FA-PEG) spacer (5000 Da) displayed a higher efficiency in targeting folate receptor (FR) + HPV-infected cells without increasing any inherent cytotoxicity. Targeted liposomally delivered ATO also displayed superior selectivity and efficiency in inducing higher cell apoptosis in HPV-positive cells per unit of arsenic taken up than free ATO, in contrast to HT-3. These findings may hold promise in improving the management of HPV-associated cancers.

scholarly journals Assessment of Intracellular Delivery Potential of Novel Sustainable Poly(δ-decalactone)-Based Micelles

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 726
Author(s):  
Kuldeep Kumar Bansal ◽  
Ezgi Özliseli ◽  
Gaurav Kumar Saraogi ◽  
Jessica M. Rosenholm
Keyword(s):  
Drug Delivery ◽  
Folic Acid ◽  
Folate Receptor ◽  
In Vitro Cytotoxicity ◽  
Uptake Efficiency ◽  
Drug Delivery Carrier ◽  
Intracellular Drug Delivery ◽  
Copolymer Micelles ◽  
Model Drug

Biodegradable polymers from renewable resources have attracted much attention in recent years within the biomedical field. Lately, poly(δ-decalactone) based copolymer micelles have emerged as a potential drug delivery carrier material as a sustainable alternative to fossil-based polymers. However, their intracellular drug delivery potential is not yet investigated and therefore, in this work, we report on the synthesis and cellular uptake efficiency of poly(δ-decalactone) based micelles with or without a targeting ligand. Folic acid was chosen as a model targeting ligand and Rhodamine B as a fluorescent tracer to demonstrate the straightforward functionalisation aspect of copolymers. The synthesis of block copolymers was accomplished by a combination of facile ring-opening polymerisation and click chemistry to retain the structure uniformity. The presence of folic acid on the surface of micelles with diameter ~150 nm upsurge the uptake efficiency by 1.6 fold on folate receptor overexpressing MDA-MB-231 cells indicating the attainment of targeting using ligand functionality. The drug delivery capability of these carriers was ascertained by using docetaxel as a model drug, whereby the in vitro cytotoxicity of the drug was significantly increased after incorporation in micelles 48 h post incubation. We have also investigated the possible endocytosis route of non-targeted micelles and found that caveolae-mediated endocytosis was the preferred route of uptake. This work strengthens the prospect of using novel bio-based poly(δ-decalactone) micelles as efficient multifunctional drug delivery nanocarriers towards medical applications.

Adriamycin Loaded and Folic Acid Coated Zn-MOF for Tumor-Targeted Chemotherapy of Cervical Cancer

2019 ◽  
Vol 9 (11) ◽  
pp. 1535-1541
Author(s):  
Jing Sun ◽  
Xiang-E Long ◽  
Rong Li ◽  
Chao-Feng Hu ◽  
Xiao-Hong Ge
Keyword(s):  
Folic Acid ◽  
Drug Targeting ◽  
Folate Receptor ◽  
Metal Organic Framework ◽  
Drug Carriers ◽  
Spherical Particles ◽  
Metal Organic ◽  
Cervical Tumors

The drug delivery systems (DDSs) introduced in recent years have been wide recognized to greatly evaluate the efficacy of drugs. With the aim to increase drug targeting to tumors as well as decrease the side effect of both drug and drug carriers, this study has developed a hybrid DDS by incorporation zinc based metal-organic framework (Zn-MOF) and folic acid (FA). Moreover, adriamycin (Adr) as a model anticancer drug was loaded into the FA/Zn-MOF nanoparticle. The as-prepared FA/ZnMOF/Adr was expected to serve as a tumor targeting DDS that capable of effectively delivering Adr to cervical tumors. Characterization revealed that FA/Zn-MOF/Adr was nanosized spherical particles with high stability and biocompatibility. Most importantly, the FA/Zn-MOF/Adr could realize positive targeting to FA overexpressed HeLa cells through folate receptor (FR). Therefore, FA/Zn-MOF/Adr resulted enhanced in vitro and in vivo anticancer benefits than than free Adr or FA unmodified Zn-MOF/Adr.

scholarly journals Synthesis and evaluation of radiolabeled, folic acid-PEG conjugated, amino silane coated magnetic nanoparticles in tumor bearing Balb/C mice

Nukleonika ◽  
2015 ◽  
Vol 60 (3) ◽  
pp. 497-502 ◽  
Author(s):  
Javad Razjouyan ◽  
Hamidreza Zolata ◽  
Omid Khayat ◽  
Fereidoun Nowshiravan ◽  
Nami Shadanpour ◽  
...  
Keyword(s):  
Folic Acid ◽  
Folate Receptor ◽  
Superparamagnetic Iron Oxide ◽  
Fibroblast Cell ◽  
Mouse Fibroblast ◽  
Tumor Uptake ◽  
Mri Imaging ◽  
Tumor Bearing ◽  
Biodistribution Studies

Abstract To design a potent agent for positron emission tomography/magnetic resonance imaging (PET/MRI) imaging and targeted magnetic hyperthermia-radioisotope cancer therapy radiolabeled surface modified superparamagnetic iron oxide nanoparticles (SPIONs) were used as nanocarriers. Folic acid was conjugated for increasing selective cellular binding and internalization through receptor-mediated endocytosis. SPIONs were synthesized by the thermal decomposition of tris (acetylacetonato) iron (III) to achieve narrow and uniform nanoparticles. To increase the biocompatibility of SPIONs, they were coated with (3-aminopropyl) triethoxysilane (APTES), and then conjugated with synthesized folic acid-polyethylene glycol (FA-PEG) through amine group of (3-aminopropyl) triethoxysilane. Finally, the particles were labeled with 64Cu (t1/2 = 12.7 h) using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxy succinimide ester) DOTA-NHS chelator. After the characterization of SPIONs, their cellular internalization was evaluated in folate receptor (FR) overexpressing KB (established from a HeLa cell contamination) and mouse fibroblast cell (MFB) lines. Eventually, active and passive targeting effects of complex were assessed in KB tumor-bearing Balb/C mice through biodistribution studies. Synthesized bare SPIONs had low toxicity effect on healthy cells, but surface modification increased their biocompatibility. Moreover, KB cells viability was reduced when using folate conjugated SPIONs due to FR-mediated endocytosis, while having little effect on healthy cells (MFB). Moreover, this radiotracer had tolerable in vivo characteristics and tumor uptake. In the receptor blocked case, tumor uptake was decreased, indicating FR-specific uptake in tumor tissue while enhanced permeability and retention effect was major mechanism for tumor uptake.

Sign in / Sign up

Export Citation Format

Share Document