Near infrared II laser controlled free radical release nanogenerator for synergistic nitric oxide and alkyl radical therapy of breast cancer

Nanoscale ◽  
2021 ◽  
Author(s):  
Weiwei Wu ◽  
Yan Yang ◽  
Zhuoying Liang ◽  
Xiling Song ◽  
Yadong Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nitric Oxide ◽  
Free Radical ◽  
Cancer Therapy ◽  
Alkyl Radical ◽  
Near Infrared ◽  
Combined Therapy ◽  
Generation Property ◽  
Radical Therapy ◽  
First Time

Recently, alkyl radical has attracted much attention in cancer therapy due to its oxygen-independent generation property. For the first time, alkyl radical and nitric oxide (NO) combined therapy is demonstrated...

scholarly journals Near-Infrared Light-Responsive Nitric Oxide Delivery Platform for Enhanced Radioimmunotherapy

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Xuanfang Zhou ◽  
Zhouqi Meng ◽  
Jialin She ◽  
Yaojia Zhang ◽  
Xuan Yi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Delivery System ◽  
Near Infrared ◽  
Combined Therapy ◽  
Tumor Model ◽  
Immune Checkpoint Blockade ◽  
Infrared Light ◽  
High Dose ◽  
High Concentration ◽  
Therapy Strategy

AbstractRadiotherapy (RT) is a widely used way for cancer treatment. However, the efficiency of RT may come with various challenges such as low specificity, limitation by resistance, high dose and so on. Nitric oxide (NO) is known a very effective radiosensitizer of hypoxic tumor. However, NO cannot circulate in body with high concentration. Herein, an NIR light-responsive NO delivery system is developed for controlled and precisely release of NO to hypoxic tumors during radiotherapy. Tert-Butyl nitrite, which is an efficient NO source, is coupled to Ag2S quantum dots (QDs). NO could be generated and released from the Ag2S QDs effectively under the NIR irradiation due to the thermal effect. In addition, Ag is also a type of heavy metal that can benefit the RT therapy. We demonstrate that Ag2S NO delivery platforms remarkably maximize radiotherapy effects to inhibit tumor growth in CT26 tumor model. Furthermore, immunosuppressive tumor microenvironment is improved by our NO delivery system, significantly enhancing the anti-PD-L1 immune checkpoint blockade therapy. 100% survival rate is achieved by the radio-immune combined therapy strategy based on the Ag2S NO delivery platforms. Our results suggest the promise of Ag2S NO delivery platforms for multifunctional cancer radioimmunotherapy.

scholarly journals NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Zhang ◽  
Yadi Fan ◽  
Zhe Yang ◽  
Mo Yang ◽  
Chun-Yuen Wong
Keyword(s):  
Free Radical ◽  
Cancer Therapy ◽  
Contrast Agent ◽  
Near Infrared ◽  
Glutathione Depletion ◽  
Therapeutic Effects ◽  
Zeolitic Imidazolate Framework ◽  
Hypoxic Conditions ◽  
Light Excitation ◽  
4T1 Cells

Abstract Background Though the combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) appears to be very attractive in cancer treatment, hypoxia and overproduced glutathione (GSH) in the tumor microenvironment (TME) limit their efficacy for further application. Results In this work, a smart hypoxia-irrelevant free radical nanogenerator (AIPH/PDA@CuS/ZIF-8, denoted as APCZ) was synthesized in situ via coating copper sulphide (CuS)-embedded zeolitic imidazolate framework-8 (ZIF-8) on the free radical initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH)-loaded polydopamine (PDA). APCZ showed promising GSH-depleting ability and near-infrared (NIR)-II photothermal performance for combined cancer therapy. Once internalized by 4T1 cells, the outer ZIF-8 was rapidly degraded to trigger the release of CuS nanoparticles (NPs), which could react with local GSH and sequentially hydrogen peroxide (H2O2) to form hydroxyl radical (·OH) for CDT. More importantly, the hyperthermia generated by APCZ upon 1064 nm laser excitation not only permitted NIR-II photothermal therapy (PTT) and promoted CDT, but also triggered the decomposition of AIPH to give toxic alkyl radical (·R) for oxygen-independent PDT. Besides, the PDA together with CuS greatly decreased the GSH level and resulted in significantly enhanced PDT/CDT in both normoxic and hypoxic conditions. The tumors could be completely eradicated after 14 days of treatment due to the prominent therapeutic effects of PTT/PDT/CDT. Additionally, the feasibility of APCZ as a photoacoustic (PA) imaging contrast agent was also demonstrated. Conclusions The novel APCZ could realize the cooperative amplification effect of free radicals-based therapies by NIR-II light excitation and GSH consumption, and act as a contrast agent to improve PA imaging, holding tremendous potential for efficient diagnosis and treatment of deep-seated and hypoxic tumors. Graphic abstract

scholarly journals The synergistic antitumor effect of combined Anti-Human Epidermal Growth Factor Receptor 2 (HER2) antibody and Gamma Interferon therapy to Ab resistant breast cancer cells

2019 ◽  
Author(s):  
Toshihiko Gocho ◽  
Hiromichi Tsuchiya ◽  
Shotaro Kamijo ◽  
Yoshitaka Yamazaki ◽  
Yui Akita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Breast Cancer Cells ◽  
Antitumor Effect ◽  
Combined Therapy ◽  
Her2 Positive ◽  
Ifn Γ ◽  
Positive Breast Cancer

AbstractAnti-HER2 antibody is molecular targeted antibody for cancer therapy. Approximately 20% of breast cancers are characterized by overexpression of HER2 protein. However, the recurrence rate was 30% and the metastasis rate was 18% one year after treatment of Anti-HER2 antibody for HER2 positive breast cancer. The resistance to antibody treatment is a major problem for patients. We previously reported that Anti-HER2 antibody and Gamma Interferon (IFN-γ) combined therapy showed higher anti-tumor effect than usual therapy in vitro and in vivo mouse experiments.In this study, we evaluated whether anti-HER2 antibody and IFN-γ combined therapy shows good synergistic effect against drug resistant HER2 positive breast cancer cells and higher antitumor effect than conventional clinical treatment. The resistant cell lines were made under the continuous presence of antibody until cell growth was not affected by the drug. We divided the resistant cells into the appropriate number of groups, which we and treated with anti-cancer therapy. We evaluated the antitumor effect for both in vitro study and in vivo mouse xenograft model prepared with the same immunogenicity. And we investigated the differences of immunofluorescence staining of CD8, Gr-1 and PDL-1 in tissues, especially related to immunity system.The combined therapy showed significantly higher anti-tumor effect than other groups in vitro and in vivo experiments. The combined therapy affects anti-tumor immunity in this immunofluorescence experiment. Taken together, we showed the possibility that combined therapy could be an effective treatment option for anti-HER2 antibody resistant breast cancer, helping patients suffering from cancer progression after developing treatment resistance.

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 Magnetoliposomes Containing Calcium Ferrite Nanoparticles for Applications in Breast Cancer Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 477 ◽  
Author(s):  
Pereira ◽  
Cardoso ◽  
Rodrigues ◽  
Amorim ◽  
Amaral ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Fluorescence Emission ◽  
Calcium Ferrite ◽  
Antitumor Drugs ◽  
Breast Cancer Therapy ◽  
Visible Absorption ◽  
Uv Visible ◽  
First Time ◽  
Potential Antitumor

Magnetoliposomes containing calcium ferrite (CaFe2O4) nanoparticles were developed and characterized for the first time. CaFe2O4 nanoparticles were covered by a lipid bilayer or entrapped in liposomes forming, respectively, solid or aqueous magnetoliposomes as nanocarriers for new antitumor drugs. The magnetic nanoparticles were characterized by UV/Visible absorption, XRD, HR-TEM, and SQUID, exhibiting sizes of 5.2 ± 1.2 nm (from TEM) and a superparamagnetic behavior. The magnetoliposomes were characterized by DLS and TEM. The incorporation of two new potential antitumor drugs (thienopyridine derivatives) specifically active against breast cancer in these nanosystems was investigated by fluorescence emission and anisotropy. Aqueous magnetoliposomes, with hydrodynamic diameters around 130 nm, and solid magnetoliposomes with sizes of ca. 170 nm, interact with biomembranes by fusion and are able to transport the antitumor drugs with generally high encapsulation efficiencies (70%). These fully biocompatible drug-loaded magnetoliposomes can be promising as therapeutic agents in future applications of combined breast cancer therapy.

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