scholarly journals Magnetic tri-bead microrobot assisted near-infrared triggered combined photothermal and chemotherapy of cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoxia Song ◽  
Zhi Chen ◽  
Xue Zhang ◽  
Junfeng Xiong ◽  
Teng Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
Stimuli Responsive ◽  
Lung Cancer Cell ◽  
Precise Movement ◽  
Photothermal Property

AbstractMagnetic micro/nanorobots attracted much attention in biomedical fields because of their precise movement, manipulation, and targeting abilities. However, there is a lack of research on intelligent micro/nanorobots with stimuli-responsive drug delivery mechanisms for cancer therapy. To address this issue, we developed a type of strong covalently bound tri-bead drug delivery microrobots with NIR photothermal response azobenzene molecules attached to their carboxylic surface groups. The tri-bead microrobots are magnetic and showed good cytocompatibility even when their concentration is up to 200 µg/mL. In vitro photothermal experiments demonstrated fast NIR-responsive photothermal property; the microrobots were heated to 50 °C in 4 min, which triggered a significant increase in drug release. Motion control of the microrobots inside a microchannel demonstrated the feasibility of targeted therapy on tumor cells. Finally, experiments with lung cancer cells demonstrated the effectiveness of targeted chemo-photothermal therapy and were validated by cell viability assays. These results indicated that tri-bead microrobots have excellent potential for targeted chemo-photothermal therapy for lung cancer cell treatment.

scholarly journals Stimuli-Responsive, Plasmonic Nanogel for Dual Delivery of Curcumin and Photothermal Therapy for Cancer Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Fadak Howaili ◽  
Ezgi Özliseli ◽  
Berrin Küçüktürkmen ◽  
Seyyede Mahboubeh Razavi ◽  
Majid Sadeghizadeh ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Photothermal Therapy ◽  
Drug Carrier ◽  
Drug Loading ◽  
Stimuli Responsive ◽  
Ph Responsive ◽  
Cytotoxicity Studies

Nanogels (Ng) are crosslinked polymer-based hydrogel nanoparticles considered to be next-generation drug delivery systems due to their superior properties, including high drug loading capacity, low toxicity, and stimuli responsiveness. In this study, dually thermo-pH-responsive plasmonic nanogel (AuNP@Ng) was synthesized by grafting poly (N-isopropyl acrylamide) (PNIPAM) to chitosan (CS) in the presence of a chemical crosslinker to serve as a drug carrier system. The nanogel was further incorporated with gold nanoparticles (AuNP) to provide simultaneous drug delivery and photothermal therapy (PTT). Curcumin's (Cur) low water solubility and low bioavailability are the biggest obstacles to effective use of curcumin for anticancer therapy, and these obstacles can be overcome by utilizing an efficient delivery system. Therefore, curcumin was chosen as a model drug to be loaded into the nanogel for enhancing the anticancer efficiency, and further, its therapeutic efficiency was enhanced by PTT of the formulated AuNP@Ng. Thorough characterization of Ng based on CS and PNIPAM was conducted to confirm successful synthesis. Furthermore, photothermal properties and swelling ratio of fabricated nanoparticles were evaluated. Morphology and size measurements of nanogel were determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Nanogel was found to have a hydrodynamic size of ~167 nm and exhibited sustained release of curcumin up to 72 h with dual thermo-pH responsive drug release behavior, as examined under different temperature and pH conditions. Cytocompatibility of plasmonic nanogel was evaluated on MDA-MB-231 human breast cancer and non-tumorigenic MCF 10A cell lines, and the findings indicated the nanogel formulation to be cytocompatible. Nanoparticle uptake studies showed high internalization of nanoparticles in cancer cells when compared with non-tumorigenic cells and confocal microscopy further demonstrated that AuNP@Ng were internalized into the MDA-MB-231 cancer cells via endosomal route. In vitro cytotoxicity studies revealed dose-dependent and time-dependent drug delivery of curcumin loaded AuNP@Ng/Cur. Furthermore, the developed nanoparticles showed an improved chemotherapy efficacy when irradiated with near-infrared (NIR) laser (808 nm) in vitro. This work revealed that synthesized plasmonic nanogel loaded with curcumin (AuNP@Ng/Cur) can act as stimuli-responsive nanocarriers, having potential for dual therapy i.e., delivery of hydrophobic drug and photothermal therapy.

A selective drug delivery system based on phospholipid-type nanobubbles for lung cancer therapy

Nanomedicine ◽  
2020 ◽  
Vol 15 (27) ◽  
pp. 2689-2705
Author(s):  
Ming-Hsien Chan ◽  
Yung-Chieh Chan ◽  
Ru-Shi Liu ◽  
Michael Hsiao
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Lung Cancer Cell ◽  
Microtubule Stabilization ◽  
Selective Targeting ◽  
Lung Cancer Therapy

Aim: To develop a micelle-type nanobubble decorated with fluorescein-5-isothiocyanate-conjugated transferrin, with encapsulation of paclitaxel (PTX@FT-NB) for lung cancer treatment. Materials & methods: PTX@FT-NBs were characterized to determine their physicochemical properties, structural stability and cytotoxicity. Lung cancer cell and mouse xenograft tumor models were used to evaluate the therapeutic effectiveness of PTX@FT-NB. Results: The PTX@FT-NBs not only showed selective targeting to lung cancer cells but also inhibited tumor growth significantly via paclitaxel release. Furthermore, paclitaxel-induced microtubule stabilization demonstrated the release of the drug from PTX@FT-NB in the targeted tumor cell both in vitro and in vivo. Conclusion: PTX@FT-NB has the potential as an anticancer nanocarrier against lung cancer cells because of its specific targeting and better drug delivery capacity.

scholarly journals Tumor-Intrinsic Response to IFNγ Shapes the Tumor Microenvironment and Anti-PD-1 Response in NSCLC

2019 ◽  
Author(s):  
Bonnie L. Bullock ◽  
Abigail K. Kimball ◽  
Joanna M. Poczobutt ◽  
Howard Y. Li ◽  
Jeff W. Kwak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Rna Seq ◽  
Lung Cancer Cell ◽  
Immunocompetent Mouse ◽  
Lung Cancer Patients ◽  
T Cell Infiltration ◽  
Basal Expression

AbstractTargeting PD-1/ PD-L1 is only effective in ~20% of lung cancer patients, but determinants of this response are poorly defined. We previously observed differential responses of two murine K-Ras lung cancer cell lines to anti-PD-1 therapy: CMT167 tumors were eliminated while LLC tumors were resistant. The goal of this study was to define mechanism(s) mediating this difference. RNA-Seq analysis of cancer cells recovered from lung tumors revealed that CMT167 cells induced an IFNγ signature that was absent in LLC cells. Silencing Ifngr1 in CMT167 resulted in tumors resistant to IFNγ and anti-PD-1 therapy. Conversely, LLC cells had high basal expression of Socs1, an inhibitor of IFNγ. Silencing Socs1 increased response to IFNγ in vitro and sensitized tumors to anti-PD-1. This was associated with a reshaped TME, characterized by enhanced T cell infiltration and enrichment of PD-L1 high myeloid cells. These studies demonstrate that targeted enhancement of tumor-intrinsic IFNγ signaling can induce of cascade of changes associated with increased therapeutic vulnerability.SummaryMechanisms regulating response to anti-PD-1 therapy in lung cancer are not well defined. This study, using orthotopic immunocompetent mouse models of lung cancer, demonstrates that intrinsic sensitivity of cancer cells to IFNγ determines anti-PD-1 responsiveness through alterations in the tumor microenvironment.

scholarly journals Improving Plasmonic Photothermal Therapy of Lung Cancer Cells with Anti-EGFR Targeted Gold Nanorods

Nanomaterials ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1307 ◽  
Author(s):  
Oscar Knights ◽  
Steven Freear ◽  
James R. McLaughlan
Keyword(s):  
Lung Cancer ◽  
Minimally Invasive ◽  
Cancer Cells ◽  
Gold Nanorods ◽  
Photothermal Therapy ◽  
Continuous Wave ◽  
Treatment Options ◽  
Lung Cancer Cells ◽  
Heat Conducting

Lung cancer is a particularly difficult form of cancer to diagnose and treat, due largely to the inaccessibility of tumours and the limited available treatment options. The development of plasmonic gold nanoparticles has led to their potential use in a large range of disciplines, and they have shown promise for applications in this area. The ability to functionalise these nanoparticles to target to specific cancer types, when combined with minimally invasive therapies such as photothermal therapy, could improve long-term outcomes for lung cancer patients. Conventionally, continuous wave lasers are used to generate bulk heating enhanced by gold nanorods that have accumulated in the target region. However, there are potential negative side-effects of heat-induced cell death, such as the risk of damage to healthy tissue due to heat conducting to the surrounding environment, and the development of heat and drug resistance. In this study, the use of pulsed lasers for photothermal therapy was investigated and compared with continuous wave lasers for gold nanorods with a surface plasmon resonance at 850 nm, which were functionalised with anti-EGFR antibodies. Photothermal therapy was performed with both laser systems, on lung cancer cells (A549) in vitro populations incubated with untargeted and targeted nanorods. It was shown that the combination of pulse wave laser illumination of targeted nanoparticles produced a reduction of 93 % ± 13 % in the cell viability compared with control exposures, which demonstrates a possible application for minimally invasive therapies for lung cancer.

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.

Stimuli-responsive Drug Delivery Nanocarriers in the Treatment of Breast Cancer

2020 ◽  
Vol 27 (15) ◽  
pp. 2494-2513 ◽  
Author(s):  
João A. Oshiro-Júnior ◽  
Camila Rodero ◽  
Gilmar Hanck-Silva ◽  
Mariana R. Sato ◽  
Renata Carolina Alves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Therapy ◽  
Near Infrared ◽  
Stimuli Responsive ◽  
Breast Cancer Therapy ◽  
Physical Stimuli ◽  
Pharmaceutical Properties

Stimuli-responsive drug-delivery nanocarriers (DDNs) have been increasingly reported in the literature as an alternative for breast cancer therapy. Stimuli-responsive DDNs are developed with materials that present a drastic change in response to intrinsic/chemical stimuli (pH, redox and enzyme) and extrinsic/physical stimuli (ultrasound, Near-infrared (NIR) light, magnetic field and electric current). In addition, they can be developed using different strategies, such as functionalization with signaling molecules, leading to several advantages, such as (a) improved pharmaceutical properties of liposoluble drugs, (b) selectivity with the tumor tissue decreasing systemic toxic effects, (c) controlled release upon different stimuli, which are all fundamental to improving the therapeutic effectiveness of breast cancer treatment. Therefore, this review summarizes the use of stimuli-responsive DDNs in the treatment of breast cancer. We have divided the discussions into intrinsic and extrinsic stimuli and have separately detailed them regarding their definitions and applications. Finally, we aim to address the ability of these stimuli-responsive DDNs to control the drug release in vitro and the influence on breast cancer therapy, evaluated in vivo in breast cancer models.

scholarly journals NUCKS Promotes the Proliferation, Migration and Invasion of Lung Cancer Cells Through Pi3k/Akt Signalling Pathway

2021 ◽  
Vol 44 (2) ◽  
pp. E55-61
Author(s):  
Cheng Hu ◽  
Qian Zha ◽  
Ping Hua ◽  
Lina Xiao ◽  
Deng Pan
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Lung Cancer Cell Line ◽  
Signalling Pathway ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Lung Cancer Cell

Purpose: Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) overexpression has been reported in various types of cancers. The purpose of this study is to clarify the role of NUCKS, underlying the involvement of non-small-cell lung cancer, in the progression of lung cancer. Methods: The small interfering ribonucleic acid (siRNA) of NUCKS was transfected into a lung cancer cell line (NCI-H460, A549, NCI-H1299 and NCI-H1975). Functional experiments (MTT assay, Annexin V-FITC/PI double staining assay, colony formation assay, wound healing assay and Transwell assay) were performed to measure the effects of NUCKS on lung cancer cell viability, migration, invasion and apoptosis. Results: NUCKS was found to be up-regulated in lung cancer cells. Knockdown of NUCKS significantly altered lung cancer cell apoptosis, proliferation colony formation, invasion and migration. Moreover, knockdown of NUCKS attenuated the activation of the PI3K/AKT pathway in lung cancer cells. Conclusion: NUCKS was overexpressed in lung cancer cells and played an important role in lung cancer by increasing cell growth through the PI3K/AKT signalling pathway. This in vitro study suggested NUCKS should be evaluated in a clinical setting as a novel biomarker and potential therapeutic target for lung cancer.

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