scholarly journals Targeted Co-Delivery of siRNA and Methotrexate for Tumor Therapy via Mixed Micelles

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 92 ◽  
Author(s):  
Fei Hao ◽  
Robert Lee ◽  
Chunmiao Yang ◽  
Lihuang Zhong ◽  
Yating Sun ◽  
...  
Keyword(s):  
Delivery System ◽  
Self Assembly ◽  
Target Gene ◽  
Mixed Micelles ◽  
Folate Receptor ◽  
Tumor Therapy ◽  
Narrow Particle Size Distribution ◽  
Combination Drug ◽  
Effective Carrier

A combination of chemotherapeutic drugs and siRNA is emerging as a new modality for cancer therapy. A safe and effective carrier platform is needed for combination drug delivery. Here, a functionalized mixed micelle-based delivery system was developed for targeted co-delivery of methotrexate (MTX) and survivin siRNA. Linolenic acid (LA) was separately conjugated to branched polyethlenimine (b-PEI) and methoxy-polyethyleneglycol (mPEG). MTX was then conjugated to LA-modified b-PEI (MTX-bPEI-LA) to form a functionalized polymer-drug conjugate. Functionalized mixed micelles (M-MTX) were obtained by the self-assembly of MTX-bPEI-LA and LA-modified mPEG (mPEG-LA). M-MTX had a narrow particle size distribution and could successfully condense siRNA at an N/P ratio of 16/1. M-MTX/siRNA was selectively taken up by HeLa cells overexpressing the folate receptor (FR) and facilitated the release of the siRNA into the cytoplasm. In vitro, M-MTX/siRNA produced a synergy between MTX and survivin siRNA and markedly suppressed survivin protein expression. In tumor-bearing mice, M-MTX/Cy5-siRNA showed an elevated tumor uptake. In addition, M-MTX/siRNA inhibited tumor growth. Immunohistochemistry and a western blot analysis showed a significant target gene downregulation. In conclusion, M-MTX/siRNA was highly effective as a delivery system and may serve as a model for the targeted co-delivery of therapeutic agents.

scholarly journals In Vitro Cytotoxicity and Antitumor Activity of Dual-Targeting Drug Delivery System Based on Modified Magnetic Carbon by Folate

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jinglei Du ◽  
Qiang Li ◽  
Lin Chen ◽  
Shicai Wang ◽  
Li Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Hela Cells ◽  
Folate Receptor ◽  
Drug Loading ◽  
Magnetic Characteristics ◽  
Loading Capacity ◽  
Dual Targeting

A dual-targeting drug delivery system (DTDDS) with magnetic targeting and active targeting was obtained to improve the targeting and drug-loading capacity of magnetic drug nanocarriers. An ultraviolet-visible spectrophotometer and flow cytometry were used to investigate the drug-loading and release capacity, cytotoxicity, and inhibition of tumor cell proliferation, separately. Results show that DTDDS has obvious magnetic characteristics, on which the modification amount of folic acid is 64.82 mg g-1. Doxorubicin was taken as a template drug to evaluate its drug-loading capacity, which was as high as 577.12 mg g-1. Good biocompatibility and low cytotoxicity of DTDDS were further confirmed. Moreover, DTDDS can target the folate receptor on the surface of HeLa cells and deliver doxorubicin into HeLa cells, thereby increasing the proliferation inhibition for cancer cells. Therefore, this new dual-targeting drug delivery system shows potential in significantly reducing the toxic side effects of chemotherapy and improving chemotherapy efficiency.

Self-Assembly Drug Delivery System Based on Programmable Dendritic Peptide Applied in Multidrug Resistance Tumor Therapy

2017 ◽  
Vol 38 (21) ◽  
pp. 1700490 ◽  
Author(s):  
Si Chen ◽  
Jin-Xuan Fan ◽  
Wen-Xiu Qiu ◽  
Li-Han Liu ◽  
Han Cheng ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Multidrug Resistance ◽  
Drug Delivery System ◽  
Delivery System ◽  
Self Assembly ◽  
Tumor Therapy

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

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.

scholarly journals Preparation and Characterization of Novel Perfluorooctyl Bromide Nanoparticle as Ultrasound Contrast Agent via Layer-by-Layer Self-Assembly for Folate-Receptor-Mediated Tumor Imaging

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Yue Hu ◽  
Yong Wang ◽  
Jianshuai Jiang ◽  
Baosan Han ◽  
Shengmin Zhang ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Self Assembly ◽  
Folate Receptor ◽  
Layer By Layer ◽  
The Novel ◽  
Chitosan Derivative ◽  
Glycol Chitosan ◽  
Targeted Nanoparticles ◽  
Perfluorooctyl Bromide

A folate-polyethylene glycol-chitosan derivative was synthesized and its structure was characterized. An optimal perfluorooctyl bromide nanocore template was obtained via utilizing the ultrasonic emulsification method combining with orthogonal design. The targeted nanoparticles containing targeted shell of folate-polyethylene glycol-chitosan derivative and perfluorooctyl bromide nanocore template of ultrasound imaging were prepared successfully by exploiting layer-by-layer self-assembly as contrast agent for ultrasound. Properties of the novel perfluorooctyl bromide nanoparticle were extensively studied by Dynamic Light Scattering and Transmission Electron Microscopy. The targeted nanoparticle diameter, polydispersity, and zeta potential are around 229.5 nm, 0.205, and44.7±0.6 mV, respectively. The study revealed that spherical core-shell morphology was preserved. Excellent stability of targeted nanoparticle is evidenced by two weeks of room temperature stability tests. The results of the cell viability assay and the hemolysis test confirmed that the targeted nanoparticle has an excellent biocompatibility for using in cell studies and ultrasound imaging in vivo. Most importantly, in vitro cell experiments demonstrated that an increased amount of targeted nanoparticles was accumulated in hepatocellular carcinoma cell line Bel7402 relative to hepatoma cell line L02. And targeted nanoparticles had also shown better ultrasound imaging abilities in vitro. The data suggest that the novel targeted nanoparticle may be applicable to ultrasonic molecular imaging of folate-receptor overexpressed tumor.

scholarly journals Synergetic therapy of glioma mediated by a dual delivery system loading α-mangostin and doxorubicin through cell cycle arrest and apoptotic pathways

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Wen Nie ◽  
Xin Zan ◽  
Ting Yu ◽  
Mengni Ran ◽  
Zehua Hong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Delivery System ◽  
Self Assembly ◽  
Chemotherapy Response ◽  
Cyclin E1 ◽  
Normal Tissues ◽  
Cycle Arrest ◽  
Dynamics Simulations

Abstract Two of the biggest hurdles in the deployment of chemotherapeutics against glioma is a poor drug concentration at the tumor site and serious side effects to normal tissues. Nanocarriers delivering different drugs are considered to be one of the most promising alternatives. In this study, a dual delivery system (methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL)) loaded with α-mangostin (α-m) and doxorubicin (Dox) was decorated and constructed by self-assembly to determine its ability to treat glioma. Molecular dynamics simulations showed that MPEG-PCL could provide ideal interaction positions for both α-m and Dox, indicating that the two drugs could be loaded into MPEG-PCL. Based on the in vitro results, MPEG-PCL loaded with α-m and Dox (α-m-Dox/M) with a size of 25.68 nm and a potential of −1.51 mV was demonstrated to significantly inhibit the growth and promote apoptosis in Gl261, C6 and U87 cells, and the effects of the combination were better than each compound alone. The mechanisms involved in the suppression of glioma cell growth were blockage of the cell cycle in S phase by inhibition of CDK2/cyclin E1 and promotion of apoptosis through the Bcl-2/Bax pathway. The synergetic effects of α-m-Dox/M effectively inhibited tumor growth and prolonged survival time without toxicity in mouse glioma models by inducing glioma apoptosis, inhibiting glioma proliferation and limiting tumor angiogenesis. In conclusion, a codelivery system was synthesized to deliver α-m and Dox to the glioma, thereby suppressing the development of glioma by the mechanisms of cell cycle arrest and cellular apoptosis, which demonstrated the potential of this system to improve the chemotherapy response of glioma.

scholarly journals Acidic microenvironment responsive polymeric MOF-based nanoparticles induce immunogenic cell death for combined cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaoli Zhang ◽  
Yi Lu ◽  
Die Jia ◽  
Wei Qiu ◽  
Xianbin Ma ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cell Death ◽  
Drug Delivery System ◽  
Delivery System ◽  
Tumor Therapy ◽  
Immunogenic Cell Death ◽  
Innovative Drug ◽  
Acidic Microenvironment

Abstract Background The complex tumor microenvironment and non-targeting drugs limit the efficacy of clinical tumor therapy. For ensuring the accurate delivery and maximal effects of anticancer drugs, it is important to develop innovative drug delivery system based on nano-strategies. Result In this study, an intracellular acidity-responsive polymeric metal organic framework nanoparticle (denoted as DIMP) has been constructed, which can co-deliver the chemotherapy agent of doxorubicin (DOX) and phototherapy agent of indocyanine green (ICG) for breast carcinoma theranostics. Specifically, DIMP possesses a suitable and stable nanometer size and can respond to the acidic microenvironment in cells, thus precisely delivering drugs into target tumor sites and igniting the biological reactions towards cell apoptosis. Following in vivo and in vitro results showed that DIMP could be effectively accumulated in tumor sites and induced powerful immunogenic cell death (ICD) effect. Conclusion The designed DIMP displayed its effectiveness in combined photo-chemotherapy with auxiliary of ICD effect under a multimodal imaging monitor. Thus, the present MOF-based strategy may offer a potential paradigm for designing drug-delivery system for image-guided synergistic tumor therapy. Graphical Abstract

scholarly journals Synthesis, Characterization, Self-Assembly, and Irritation Studies of Polyglyceryl-10 Caprylates

Polymers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 294 ◽  
Author(s):  
Guangyan Zhang ◽  
Chenhui Bao ◽  
Kaiqiao Fu ◽  
Yaolin Lin ◽  
Tianlong Li ◽  
...  
Keyword(s):  
Size Distribution ◽  
Self Assembly ◽  
Water Solubility ◽  
Light Transmittance ◽  
Narrow Particle Size Distribution ◽  
Esterification Reaction ◽  
Chemical Structures ◽  
Consumer Safety

1,4-dioxane should be less than or equal to 10 ppm in finished cosmetic products according to the recommendation of the Scientific Committee on Consumer Safety, but it is often generated as a by-product during the manufacturing process of poly(ethylene glycol) (PEG)-based derivatives. In order to avoid the possible risk caused by 1,4-dioxane, it might be a good choice for preparing cosmetic ingredients by using polyglycerin (PG) instead of PEG as a hydrophilic segment. In the present study, polyglyceryl-10 caprylates were synthesized by the esterification reaction between polyglycerin-10 and caprylic acid. FTIR and 1H NMR were utilized to confirm the chemical structures of the obtained polyglyceryl-10 caprylates. Light transmittance was availed to investigate the water solubility of polyglyceryl-10 caprylates. The self-assembly behavior, size, and size distribution of polyglyceryl-10 caprylates were investigated by dynamic light scattering. The makeup cleansing effect was also evaluated by in vitro and in vivo methods. Irritation was evaluated by hen’s egg test-chorioallantoic membrane assay (HET-CAM). Results showed that polyglyceryl-10 monocaprylate could self-assemble into nanoparticles in the water at the concentration range of 2.5–10 wt% with a transparent appearance. The diameter of formed nanoparticles was around 100 nm with a narrow particle size distribution around 0.1 at the concentration of 2.5 wt% or 5 wt%. Polyglyceryl-10 monocaprylate exhibited good removal effect against makeup and excellent removal efficacy against pen eyeliner. The irritation of polyglyceryl-10 monocaprylate evaluated by HET-CAM at the concentration of 4 wt% was moderate irritant (irritation score = 8.4), which was lower than that of PEG-6 caprylic/capric glycerides (severe irritant, irritation score = 14.1). Therefore, polyglyceryl-10 monocaprylate might be a promising cosmetic ingredient for transparent makeup removing water.

A Core–Shell Polyethyleneimine-Mediated Apoptosis-Related Gene Delivery for Anti-Tumor Therapy

NANO ◽  
2020 ◽  
Vol 15 (05) ◽  
pp. 2050057
Author(s):  
Yi Liu ◽  
Qiao Wang ◽  
Minhui Chen ◽  
Yun Wang ◽  
Yu Lei ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cancer Cell ◽  
Delivery System ◽  
Tumor Therapy ◽  
Cancer Cell Line ◽  
Core Shell ◽  
Related Gene ◽  
Cmv Promoter ◽  
Apoptosis Related Gene

An apoptosis-related gene loaded to the core–shell delivery system has been fabricated to give effective tumor therapy. The gene delivery system consists of the hydrophobic poly (methyl methacrylate) (PMMA) and plasmid DNA (pDNA) loaded branched polyethyleneimine (PEI). The BBC3 gene is related to cell apoptosis and constructed in the mammal plasmid vector under the CMV promoter for overexpression. The amphiphilic PEI-PMMA nanoparticle (NP) has been developed as a DNA loaded carrier of low cytotoxicity and enhanced stability. The average NP size was 330[Formula: see text]nm with a narrow distribution. The [Formula: see text][Formula: see text]mV of the zeta potential in water showed the effect of negatively charged DNA aggregation. Gel retardation assay showed the complete PEI/pDNA (N:P) binding ratio was 125:1. The MCF-7 cancer cell line was transfected with the delivery complexes, followed by the MTT assay to evaluate anti-tumor therapy. The results showed that BBC3 gene loaded PEI-PMMA complexes have significant cancer cell inhibition. Taken together, BBC3 genes expressed after 48[Formula: see text]h transfection with PEI-PMMA NPs, and this gene therapy delivery system has cancer cells inhibition as low as 8[Formula: see text][Formula: see text]g/mL in vitro.

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