A Novel Synthesis of Fe3O4@SiO2@Au@Porous SiO2 Structure for NIR Irradiation-Induced DOX Release and Cancer Treatment

Doxorubicin (DOX) alone or in combination has been widely used for numerous cancers, including breast, lung, bladder, and so on. In this article, a core/shell/shell structured Fe3O4@SiO2@Au@porous SiO2 particles for the drug delivery and release of DOX was demonstrated, with the aid of near-infrared irradiation. Fe3O4 was used to direct the transportation and delivery of the drug-loaded composite to the target tissues and organs under an external magnetic field, the first layer of SiO2 was used for Au nanoparticle attachment, Au acted as the agent for light–thermal conversion, and the porous SiO2 was used to load DOX. The morphology of the nanoparticles was studied by transmission electron microscopy, and the porous structure was characterized by N2 adsorption/desorption curves. The drug delivery system displayed high drug loading capacity, and the release behavior was largely impacted by the environmental pH. Furthermore, the cytotoxicity of Fe3O4@SiO2@Au@porous SiO2 and DOX loaded Fe3O4@SiO2@Au@porous SiO2 was studied through in vitro 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay.

Download Full-text

Double Drug-Loaded and pH/Thermal Sensitive Multifunctional Drug Delivery System for Tumor Photoacoustic Imaging-Guided Enhanced Chemo/Photothermal Therapy

10.21203/rs.2.19618/v1 ◽

2019 ◽

Author(s):

Jun Wang ◽

Na Chen ◽

Kai Liu ◽

Yu Tu ◽

Weitao Yang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Photothermal Therapy ◽

Near Infrared ◽

Drug Loading ◽

Tumor Therapy ◽

Photothermal Effect ◽

Heterogeneous Distribution

Abstract Background: Owing to the tunability of longitudinal surface plasmon resonance (LSPR), ease of synthesizing small size and excellent stability, AuNRs have been developed as photothermal agents for cancer therapy. However, PTT alone could not kill cancer cells completely due to the local heterogeneous distribution of heat in tumors, penetration depth of light, light scattering and absorption. In addition, the treatment systems based on AuNRs hold disadvantages of loading one antitumor drug or a low therapeutic efficiency. Therefore, the construction of the AuNRs theranostic system to achieve imaging-guided dual drug delivery and enhanced photothermal therapy for tumor still remains a great challenge.Methods: The AuNRs were prepared using a seedless method. A mesoporous silica shell layer was coated on the surface of the AuNRs by sol-gel method. Double anticancer drugs, DOX and Btz, were loaded into the AuNRs@MSN nanoparticles through physical absorption and covalent conjugation, respectively.Results: The release of DOX and Btz is found pH/thermal dual responsive in vitro. Compared with AuNRs@MSN, PDA-AuNRs@MSN exhibits an increased near-infrared (NIR) absorption at 808 nm and an enhanced photothermal effect. In contrast to chemotherapy or photothermal therapy alone, the integrated D/B-PDA-AuNRs@MSN nanoparticles show higher cell apoptosis and enhanced tumor treatment efficacy in vitro and in vivo.Conclusions: In this study, we designed a double-drug loading, enhanced chemo/photothermal therapy and pH/thermal responsive drug delivery system for photoacoustic (PA) imaging-guided tumor therapy. We believe that the multifunctional D/B-PDA-AuNRs@MSN theranostic probe could serve as an effective probe for the treatment of cancers.

Download Full-text

Mesoporous Silica Encapsulated Iron Oxide-Silver Heterodimeric Nanoparticles and Their Applications in Multi-Responsive Drug Release

10.21203/rs.3.rs-910453/v1 ◽

2021 ◽

Author(s):

Xiaoting Sun ◽

Xiaohui Zhang ◽

Huazhe Yang ◽

Xiaohong Wang

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Mesoporous Silica ◽

Near Infrared ◽

Combined Therapy ◽

Drug Loading ◽

Photothermal Effect ◽

Ph Response ◽

Growth Method

Abstract Background Metal based nanomaterials play essential roles in the fields of cancer diagnosis and therapy, drug delivery and exploration. As a novel kind of metal nanocomposites, magnetic-plasmonic nanohybrids are promising candidates in combined therapy. However, few studies have demonstrated the multi-responsive drug delivery properties of the nanohybrids. In this work, novel Fe3O4-Ag heterodimer nanoparticles coated with mesoporous SiO2 were prepared for multi-responsive drug release applications. Results Seed growth method was employed to form the heterodimer particles, and a layer of mesoporous silica was coated on the particle to improve the biocompatibility of metal nanoparticles, which also acted as drug loading and release component. Characterized via infrared spectroscopy, X-Ray diffraction and transmission electron microscopy, the particles were confirmed to appear a Janus like structure with Fe3O4 and Ag hemispheres encapsulating in silica. Doxorubicin hydrochloride (DOX) was loaded on the surface of the particles for drug delivery. The drug loading efficiency, release performance and the apoptosis action of the particles on MCF-7 cells were investigated in vitro. The results showed that DOX was successfully loaded on the particles with encapsulation efficiency of 88.3% and drug loading of 30.6%. And the release amount after 48 h increased from 10.05 ± 0.19% to 68.53 ± 8.20% as the environment was tuned to acidic, indicating an obvious pH response of the particles. Simultaneously, due to the photothermal effect of Ag hemispheres, the particles had exhibited an enhanced drug release stimulated by 808 nm near infrared (NIR) irradiation. And the results of apoptosis assay were in accord with the drug release profiles. Besides, the particles could well respond to an external magnetic field, which is beneficial to particle location or recovery. Conclusion The as-prepared particles exhibit good magnetic and photothermal properties originating from Fe3O4 and Ag hemispheres respectively, which are desired features in magnetic hyperthermia and photothermal therapy. The particles also possess pH and NIR light responsive drug release properties, enabling triggered and targeted drug delivery.

Download Full-text

Sequential Drug Delivery By Injectable Macroporous Hydrogels For Combined Photodynamic-Chemotherapy

10.21203/rs.3.rs-779103/v1 ◽

2021 ◽

Author(s):

Yuanyuan Zhong ◽

Li Zhang ◽

Shian Sun ◽

Zhenghao Zhou ◽

Yunsu Ma ◽

...

Keyword(s):

Drug Delivery ◽

Near Infrared ◽

Early Stage ◽

Drug Loading ◽

Tumor Therapy ◽

Sequential Release ◽

Therapy Effect ◽

Hollow Mesoporous Silica

Abstract With hollow mesoporous silica (hMSN) and injectable macroporous hydrogel (Gel) used as the internal and external drug-loading material respectively, a sequential drug delivery system DOX-CA4P@Gel was constructed, in which combretastatin A4 phosphate (CA4P) and doxorubicin (DOX) were both loaded. The anti-angiogenic drug, CA4P was initially released due to the degradation of Gel, followed by the anti-cell proliferative drug, DOX, released from hMSN in tumor microenvironment. Results showed that CA4P was mainly released at the early stage. At 48 h, CA4P release reached 71.08%, while DOX was only 14.39%. At 144 h, CA4P was 78.20%, while DOX release significantly increased to 61.60%, showing an obvious sequential release behavior. Photodynamic properties of porphyrin endow hydrogel (φΔ(Gel)=0.91) with enhanced tumor therapy effect. In vitro and in vivo experiments showed that dual drugs treated groups have better tumor inhibition than solo drug under near infrared laser irradiation, indicating the effectivity of combined photodynamic-chemotherapy.

Download Full-text

PAMAM dendrimers in drug delivery: loading efficacy and polymer morphology

Canadian Journal of Chemistry ◽

10.1139/cjc-2017-0115 ◽

2017 ◽

Vol 95 (9) ◽

pp. 891-896 ◽

Cited By ~ 12

Author(s):

P. Chanphai ◽

L. Bekale ◽

S. Sanyakamdhorn ◽

D. Agudelo ◽

G. Bérubé ◽

...

Keyword(s):

Electron Microscopy ◽

Drug Delivery ◽

Drug Loading ◽

Polymer Surface ◽

Pamam Dendrimers ◽

Spectroscopic Methods ◽

Polymer Morphology ◽

Transmission Electron ◽

Internal Cavities

The binding efficacy of anticancer drugs doxorubicin and tamoxifen with polyamidoamine (PAMAM-G4) dendrimers was studied in aqueous solution at physiological pH. The results of multiple spectroscopic methods, transmission electron microscopy (TEM), and molecular modeling of conjugated drug–polymer were examined. Structural analysis showed that drug–polymer conjugation occurs mainly via H-bonding and hydrophilic and hydrophobic contacts. Doxorubicin forms a more stable conjugate with PAMAM-G4 than tamoxifen. The drug loading efficacy was 40%–50%. The TEM images showed major changes in the PAMAM morphology upon drug encapsulation. Modeling showed that drug is located in the polymer surface and in the internal cavities. PAMAM nanoparticles are capable of transporting doxorubicin and tamoxifen in vitro. This minireview presents the most recent work performed with the dendrimers demonstrating their usefulness for drug delivery in cancer therapy.

Download Full-text

Preparation, Characterization, and Anticancer Effects of Capsaicin-Loaded Nanoliposomes

Nutrients ◽

10.3390/nu13113995 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3995

Author(s):

Ali Al-Samydai ◽

Walhan Alshaer ◽

Emad A. S. Al-Dujaili ◽

Hanan Azzam ◽

Talal Aburjai

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Therapeutic Potential ◽

Drug Loading ◽

Cell Viability Assay ◽

Viability Assay ◽

Anticancer Effects ◽

Pharmacokinetic Properties ◽

Quantitative Analyses

Background: Medicinal plants have proven their value as a source of molecules with therapeutic potential, and recent studies have shown that capsaicin has profound anticancer effects in several types of human cancers. However, its clinical use is handicapped due to its poor pharmacokinetics. This study aims to enhance capsaicin’s pharmacokinetic properties by loading the molecule into nanoliposomes model and testing its anticancer activity. Methods: Nanoliposomes were prepared using the thin-film method, and characteristics were examined followed by qualitative and quantitative analyses of encapsulation efficiency and drug loading using HPLC at different lipid/capsaicin ratios. Cell viability assay (MTT) was used to determine IC50. Results: Capsaicin-loaded nanoliposomes showed optimum characteristics of morphology, particle size, zeta potential, and stability. In vitro anticancer activity of capsaicin and capsaicin-loaded nanoliposomes were compared against MCF7, MDA-MB-231, K562, PANC1, and A375 cell lines. Capsaicin-loaded nanoliposomes showed significant improvement in anticancer activity against cancers cell lines studied (p < 0.001), with increased selectivity against cancer cells compared to capsaicin. Conclusion: The encapsulated capsaicin nanoliposomes produced an improvement in pharmacokinetics properties, enhancing the anticancer activity and selectivity compared with capsaicin. This model seems to offer a potential for developing capsaicin formulations for the prevention and treatment of cancer.

Download Full-text

A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of theranostic agents

Nature Communications ◽

10.1038/ncomms10081 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 75

Author(s):

Hai Wang ◽

Pranay Agarwal ◽

Shuting Zhao ◽

Jianhua Yu ◽

Xiongbin Lu ◽

...

Keyword(s):

Drug Delivery ◽

Encapsulation Efficiency ◽

Near Infrared ◽

Drug Loading ◽

Eukaryotic Cell ◽

Silica Matrix ◽

High Drug ◽

Theranostic Agents

Abstract Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ∼87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.

Download Full-text

Synthesis of Ultrasmall Single-Crystal Gold–Silver Alloy Nanotriangles and Their Application in Photothermal Therapy

Nanomaterials ◽

10.3390/nano11040912 ◽

2021 ◽

Vol 11 (4) ◽

pp. 912

Author(s):

Mirko Maturi ◽

Erica Locatelli ◽

Letizia Sambri ◽

Silvia Tortorella ◽

Sašo Šturm ◽

...

Keyword(s):

Cancer Therapy ◽

Cell Viability ◽

Photothermal Therapy ◽

Near Infrared ◽

Cell Model ◽

Cell Viability Assay ◽

Cell Compatibility ◽

Viability Assay ◽

Gold Silver

Photothermal therapy has always been a very attractive anti-cancer strategy, drawing a lot of attention thanks to its excellent performance as a non-invasive and pretty safe technique. Lately, nanostructures have become the main characters of the play of cancer therapy due to their ability to absorb near-infrared radiation and efficient light-to-heat conversion. Here we present the synthesis of polyethylene glycol (PEG)-stabilized hybrid ultrasmall (<20 nm) gold–silver nanotriangles (AuAgNTrs) and their application in photothermal therapy. The obtained AuAgNTrs were deeply investigated using high-resolution transmission electron microscopy (HR-TEM). The cell viability assay was performed on U-87 glioblastoma multiforme cell model. Excellent photothermal performance of AuAgNTrs upon irradiation with NIR laser was demonstrated in suspension and in vitro, with >80% cell viability decrease already after 10 min laser irradiation with a laser power P = 3W/cm2 that was proved to be harmless to the control cells. Moreover, a previous cell viability test had shown that the nanoparticles themselves were reasonably biocompatible: without irradiation cell viability remained high. Herein, we show that our hybrid AuAgNTrs exhibit very exciting potential as nanostructures for hyperthermia cancer therapy, mostly due to their easy synthesis protocol, excellent cell compatibility and promising photothermal features.

Download Full-text

Proliferative Effect of Tilapia Fish (Oreochromis niloticus) Lectin on BALB/c Mice Splenocytes

Protein and Peptide Letters ◽

10.2174/0929866526666190911144057 ◽

2019 ◽

Vol 26 (12) ◽

pp. 887-892

Author(s):

Cynarha Daysy Cardoso da Silva ◽

Cristiane Moutinho Lagos de Melo ◽

Elba Verônica Matoso Maciel Carvalho ◽

Mércia Andréa Lino da Silva ◽

Rosiely Félix Bezerra ◽

...

Keyword(s):

Cell Proliferation ◽

Oreochromis Niloticus ◽

Cytokine Production ◽

Thymidine Incorporation ◽

Con A ◽

Cell Viability Assay ◽

Proliferative Effect ◽

Viability Assay ◽

Apoptosis And Necrosis

Background: Lectins have been studied in recent years due to their immunomodulatory activities. Objective: We purified a lectin named OniL from tilapia fish (Oreochromis niloticus) and here we analyzed the cell proliferation and cytokine production in Balb/c mice splenocytes. Methods: Cells were stimulated in vitro in 24, 48, 72 hours and 6 days with different concentrations of OniL and Con A. Evaluation of cell proliferation was performed through [3H]-thymidine incorporation, cytokines were investigated using ELISA assay and cell viability assay was performed by investigation of damage through signals of apoptosis and necrosis. Results: OniL did not promote significant cell death, induced high mitogenic activity in relation to control and Con A and stimulated the cells to release high IL-2 and IL-6 cytokines. Conclusion: These findings suggest that, like Con A, OniL lectin can be used as a mitogenic agent in immunostimulatory assays.

Download Full-text

Differential Effects of Halofuginone Enantiomers on Muscle Fibrosis and Histopathology in Duchenne Muscular Dystrophy

International Journal of Molecular Sciences ◽

10.3390/ijms22137063 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7063

Author(s):

Sharon Mordechay ◽

Shaun Smullen ◽

Paul Evans ◽

Olga Genin ◽

Mark Pines ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Motor Coordination ◽

Mdx Mice ◽

Cell Viability Assay ◽

Muscle Fibrosis ◽

Antifibrotic Therapy ◽

Racemic Form ◽

Viability Assay

Progressive loss of muscle and muscle function is associated with significant fibrosis in Duchenne muscular dystrophy (DMD) patients. Halofuginone, an analog of febrifugine, prevents fibrosis in various animal models, including those of muscular dystrophies. Effects of (+)/(−)-halofuginone enantiomers on motor coordination and diaphragm histopathology in mdx mice, the mouse model for DMD, were examined. Four-week-old male mice were treated with racemic halofuginone, or its separate enantiomers, for 10 weeks. Controls were treated with saline. Racemic halofuginone-treated mice demonstrated better motor coordination and balance than controls. However, (+)-halofuginone surpassed the racemic form’s effect. No effect was observed for (−)-halofuginone, which behaved like the control. A significant reduction in collagen content and degenerative areas, and an increase in utrophin levels were observed in diaphragms of mice treated with racemic halofuginone. Again, (+)-halofuginone was more effective than the racemic form, whereas (−)-halofuginone had no effect. Both racemic and (+)-halofuginone increased diaphragm myofiber diameters, with no effect for (−)-halofuginone. No effects were observed for any of the compounds tested in an in-vitro cell viability assay. These results, demonstrating a differential effect of the halofuginone enantiomers and superiority of (+)-halofuginone, are of great importance for future use of (+)-halofuginone as a DMD antifibrotic therapy.

Download Full-text

BDMC protects AD in vitro via AMPK and SIRT1

Translational Neuroscience ◽

10.1515/tnsci-2020-0140 ◽

2020 ◽

Vol 11 (1) ◽

pp. 319-327

Author(s):

Chenlin Xu ◽

Zijian Xiao ◽

Heng Wu ◽

Guijuan Zhou ◽

Duanqun He ◽

...

Keyword(s):

Neurodegenerative Disorder ◽

Neuroprotective Effect ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Activity Measurement ◽

Therapeutic Approaches ◽

Cell Viability Assay ◽

Viability Assay ◽

Compound C

AbstractBackgroundAlzheimer’s disease (AD) is a common neurodegenerative disorder without any satisfactory therapeutic approaches. AD is mainly characterized by the deposition of β-amyloid protein (Aβ) and extensive neuronal cell death. Curcumin, with anti-oxidative stress (OS) and cell apoptosis properties, plays essential roles in AD. However, whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, can exert a neuroprotective effect in AD remains to be elucidated.MethodsIn this study, SK-N-SH cells were used to establish an in vitro model to investigate the effects of BDMC on the Aβ1–42-induced neurotoxicity. SK-N-SH cells were pretreated with BDMC and with or without compound C and EX527 for 30 min after co-incubation with rotenone for 24 h. Subsequently, western blotting, cell viability assay and SOD and GSH activity measurement were performed.ResultsBDMC increased the cell survival, anti-OS ability, AMPK phosphorylation levels and SIRT1 in SK-N-SH cells treated with Aβ1–42. However, after treatment with compound C, an AMPK inhibitor, and EX527, an SIRT1inhibitor, the neuroprotective roles of BDMC on SK-N-SH cells treated with Aβ1–42 were inhibited.ConclusionThese results suggest that BDMC exerts a neuroprotective role on SK-N-SH cells in vitro via AMPK/SIRT1 signaling, laying the foundation for the application of BDMC in the treatment of neurodegenerative diseases related to AMPK/SIRT1 signaling.

Download Full-text