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1.
Int J Nanomedicine ; 18: 2891-2910, 2023.
Article in English | MEDLINE | ID: mdl-37283712

ABSTRACT

Introduction: Hepatocellular cancer stem cells (CSCs) play crucial roles in hepatocellular cancer initiation, development, relapse, and metastasis. Therefore, eradication of this cell population is a primary objective in hepatocellular cancer therapy. We prepared a nanodrug delivery system with activated carbon nanoparticles (ACNP) as carriers and metformin (MET) as drug (ACNP-MET), which was able to selectively eliminate hepatocellular CSCs and thereby increase the effects of MET on hepatocellular cancers. Methods: ACNP were prepared by ball milling and deposition in distilled water. Suspension of ACNP and MET was mixed and the best ratio of ACNP and MET was determined based on the isothermal adsorption formula. Hepatocellular CSCs were identified as CD133+ cells and cultured in serum-free medium. We investigated the effects of ACNP-MET on hepatocellular CSCs, including the inhibitory effects, the targeting efficiency, self-renewal capacity, and the sphere-forming capacity of hepatocellular CSCs. Next, we evaluated the therapeutic efficacy of ACNP-MET by using in vivo relapsed tumor models of hepatocellular CSCs. Results: The ACNP have a similar size, a regular spherical shape and a smooth surface. The optimal ratio for adsorption was MET: ACNP=1:4. ACNP-MET could target and inhibit the proliferation of CD133+ population and decrease mammosphere formation and renewal of CD133+ population in vitro and in vivo. Conclusion: These results not only suggest that nanodrug delivery system increased the effects of MET, but also shed light on the mechanisms of the therapeutic effects of MET and ACNP-MET on hepatocellular cancers. ACNP, as a good nano-carrier, could strengthen the effect of MET by carrying drugs to the micro-environment of hepatocellular CSCs.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Metformin , Nanoparticles , Humans , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/pathology , Charcoal , Cell Line, Tumor , Metformin/pharmacology , Neoplastic Stem Cells/pathology , Nanoparticles/therapeutic use , AC133 Antigen/metabolism , AC133 Antigen/pharmacology , Tumor Microenvironment
2.
Nanomedicine ; 27: 102192, 2020 07.
Article in English | MEDLINE | ID: mdl-32229215

ABSTRACT

Due to the lack of effective strategies on the treatment of castration resistant prostate cancer (CRPC), we established a multifunctional nanoplatform (GNS@IR820/DTX-CD133) for the synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemotherapy (CT) under the monitoring of multimodal near-infrared (NIR) fluorescence/photoacoustic (PA) imaging. Benefiting from the guided effect of CD133 antibody, GNS@IR820/DTX-CD133 can targetedly deliver the loaded drug to the tumor tissues, which can further contribute to the combined therapeutic effect. Our experimental results prove that the bio-distribution of GNS@IR820/DTX-CD133 can be monitored with NIR fluorescence and PA imaging. In addition, the application of GNS@IR820/DTX-CD133 for in vitro and in vivo therapy achieves the excellent antitumor effects of the synergistic PTT/PDT/CT strategies under the NIR-light irradiation. Therefore, as a multifunctional nanoplatform integrating the PTT/PDT/CT strategies with tumor multimodal imaging or drug tracing, GNS@IR820/DTX-CD133 has the great potential for clinical applications in the antitumor therapy of CRPC.


Subject(s)
AC133 Antigen/genetics , Nanoparticles/chemistry , Photochemotherapy , Photothermal Therapy , Prostatic Neoplasms, Castration-Resistant/therapy , AC133 Antigen/chemistry , AC133 Antigen/pharmacology , Animals , Cell Line, Tumor , Combined Modality Therapy , Disease Models, Animal , Docetaxel/chemistry , Docetaxel/pharmacology , Drug Delivery Systems , Gold/chemistry , Gold/pharmacology , Heterografts , Humans , Indocyanine Green/analogs & derivatives , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Male , Mice , Molecular Targeted Therapy , Multimodal Imaging , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/pathology
3.
PLoS One ; 14(8): e0220860, 2019.
Article in English | MEDLINE | ID: mdl-31393941

ABSTRACT

We previously reported that CD133, as a putative cancer stem cell marker, plays an important role in cell proliferation and invasion in colon cancer. To understand the role of CD133 expression in colon cancer, we evaluated the inhibitory effect of CD133 in colon cancer cells. In this study, we generated CD133knockout colon cancer cells (LoVo) using the CRISPR-Cas9 gene editing system. CD133+ colon cancer cells (LoVo) were infected with the lentiviral vector carrying CD133 gRNA and purified cell by culturing single cell colonies. CD133knockout cells was validated by western blot and flow cytometry analysis. In functional study, we observed a significant reduction in cell proliferation and colony formation in CRISPR-Cas9 mediated CD133 knockout cells in compare with control (P < 0.001). We also found the anticancer effect of stattic was dependent on CD133 expression in colon cancer cells. Although CD133knockout cells could not completely block the tumorigenic property, they showed remarkable inhibitory effects on the ability of cell migration and invasion (P < 0.001). In addition, we examined the epithelial mesenchymal transition (EMT)-related protein expression by western blot. The result clearly showed a loss of vimentin expression in CD133knockout cells. Therefore, CRISPR-Cas9 mediated CD133knockout can be an effective treatment modality for CD133+ colon cancer through reducing the characteristics of cancer stem cells.


Subject(s)
AC133 Antigen/pharmacology , Colonic Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Neoplasm Invasiveness/prevention & control , AC133 Antigen/deficiency , AC133 Antigen/genetics , CRISPR-Cas Systems/genetics , Cell Proliferation , Colonic Neoplasms/genetics , Colonic Neoplasms/therapy , Cyclic S-Oxides/pharmacology , Gene Knockout Techniques/methods , Humans , Neoplastic Stem Cells , Tumor Cells, Cultured , Vimentin/metabolism
4.
Artif Cells Nanomed Biotechnol ; 46(8): 1864-1871, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29082764

ABSTRACT

The aim of the present study was to prepare a novel CD133 aptamer modified DTX liposome system and investigate its characteristics in vitro and in vivo studies. In this study, the CD133-DTX LP was prepared by the thin-film hydration method and with the particle size of 100-120 nm. The TEM photomicrographs were smooth, sub-spherical in shape and aggregated to form small clusters. In vitro, a relatively slower DTX release profile was observed in CD133-DTX LP due to the presence of CD133 aptamers on the outer surface which might hinder the drug release. The drug release mechanism fit well with the Higuchi equation better. In cytotoxicity study, CD133 aptamers modified DTX LP significantly decreased cell proliferation and improved the therapeutic efficiency. In vivo imaging result indicated that CD133-DTX LP had very good tumour targeting ability. In vivo antitumour activity indicated that the CD133-DTX LP showed a significant antitumour activity in A549 tumour mice, with a very low systemic toxicity.


Subject(s)
AC133 Antigen , Docetaxel , Drug Delivery Systems/methods , Lung Neoplasms/drug therapy , A549 Cells , AC133 Antigen/chemistry , AC133 Antigen/pharmacokinetics , AC133 Antigen/pharmacology , Animals , Docetaxel/chemistry , Docetaxel/pharmacokinetics , Docetaxel/pharmacology , Humans , Liposomes , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Rabbits , Surface Properties
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