scholarly journals Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1019 ◽  
Author(s):  
Yuko Nishinaga ◽  
Kazuhide Sato ◽  
Hirotoshi Yasui ◽  
Shunichi Taki ◽  
Kazuomi Takahashi ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Mouse Model ◽  
Near Infrared ◽  
Luciferase Activity ◽  
Group Versus ◽  
Pleural Mesothelioma ◽  
Orthotopic Mouse Model ◽  
Nir Light

Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody–photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM.

H2O2/near-infrared light-responsive nanotheronostics for MRI-guided synergistic chemo/photothermal cancer therapy

Nanomedicine ◽  
2019 ◽  
Vol 14 (16) ◽  
pp. 2189-2207
Author(s):  
Yiming Yu ◽  
Li Zhang ◽  
Miao Wang ◽  
Zhe Yang ◽  
Leping Lin ◽  
...  
Keyword(s):  
Near Infrared ◽  
Tumor Model ◽  
Mri Contrast Agent ◽  
Infrared Light ◽  
Antitumor Effects ◽  
Mri Contrast ◽  
Nir Light ◽  
Nir Laser

Aim: To develop a H2O2/near-infrared (NIR) laser light-responsive nanoplatform (manganese-doped Prussian blue@polypyrrole [MnPB@PPy]) for synergistic chemo/photothermal cancer theranostics. Materials & methods: Doxorubicin (DOX) was loaded onto the surface of polypyrrole shells. The in vitro and in vivo MRI performance and anticancer effects of these nanoparticles (NPs) were evaluated. Results: The MnPB@PPy NPs could not only generate heat under NIR laser irradiation for cancer photothermal therapy but also act as an excellent MRI contrast agent. The loaded DOX could be triggered to release by both NIR light and H2O2 to enhance synergistic therapeutic efficacy. The antitumor effects were confirmed by in vitro cellular cytotoxicity assays and in vivo treatment in a xenograft tumor model. Conclusion: The designed H2O2/NIR light-responsive MnPB@PPy-DOX NPs hold great potential for future biomedical applications.

Intra-articular Administrated Hydrogels of Hyaluronic Acid Hybridized with Triptolide/Gold Nanoparticles for Targeted Delivery to Rheumatoid Arthritis Combined with Photothermal-chemo Therapy

2021 ◽  
Author(s):  
Chenxi Li ◽  
Rui Liu ◽  
Yurong Song ◽  
Dongjie Zhu ◽  
Liuchunyang Yu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Invasion And Migration ◽  
Nir Light ◽  
Hybrid Hydrogels ◽  
And Migration

Abstract Triptolide (TP) as a disease-modifying anti-rheumatic drug (DMARD) is effective on the treatment of rheumatoid arthritis (RA). To alleviate the toxicity and elevate therapeutic specificity, hyaluronic acid (HA) hydrogels load RGD-attached gold nanoshell containing TP are synthesized, which can be used for targeted photothermal-chemo therapy, and imaging of RA in vivo. The hydrogels system composed of thiol and tyramine modified HA conjugates has been applied artificial tissue models of cartilage for studying drug delivery and release properties. After the degradation of HA chains, heat together with drugs can be delivered to the inflammatory joints simultaneously due to the near-infrared resonance (NIR) irradiation of Au nanoshell. RA is a chronic inflamed disease, which is characterized by synovial inflammation of multiple joints, and can be penetrated with NIR light. These intra-articular administrated hybrid hydrogels combined with NIR irradiation can improve clinical arthritic conditions and inflamed joints in collagen-induced arthritis (CIA) mice, which just need a smaller dosage of TP with non-toxicity. Additionally, the TP-Au/HA hybrid hydrogels treatment reduced the invasion and migration of RA fibroblast-like synoviocytes (RA-FLSs) in vitro significantly, through reducing the phosphorylation of mTOR and p70S6K, its substrates, and confirmed that the mTOR pathway was inhibited.

scholarly journals Deep-Tissue Photothermal Therapy Using Laser Illumination at NIR-IIa Window

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Xunzhi Wu ◽  
Yongkuan Suo ◽  
Hui Shi ◽  
Ruiqi Liu ◽  
Fengxia Wu ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Near Infrared ◽  
Laser Excitation ◽  
Tumor Treatment ◽  
Deep Tissue ◽  
Laser Illumination ◽  
Nir Light ◽  
Cell Ablation

Abstract Photothermal therapy (PTT) using near-infrared (NIR) light for tumor treatment has triggered extensive attentions because of its advantages of noninvasion and convenience. The current research on PTT usually uses lasers in the first NIR window (NIR-I; 700–900 nm) as irradiation source. However, the second NIR window (NIR-II; 1000–1700 nm) especially NIR-IIa window (1300–1400 nm) is considered much more promising in diagnosis and treatment as its superiority in penetration depth and maximum permissible exposure over NIR-I window. Hereby, we propose the use of laser excitation at 1275 nm, which is approved by Food and Drug Administration for physical therapy, as an attractive technique for PTT to balance of tissue absorption and scattering with water absorption. Specifically, CuS-PEG nanoparticles with similar absorption values at 1275 and 808 nm, a conventional NIR-I window for PTT, were synthesized as PTT agents and a comparison platform, to explore the potential of 1275 and 808 nm lasers for PTT, especially in deep-tissue settings. The results showed that 1275 nm laser was practicable in PTT. It exhibited much more desirable outcomes in cell ablation in vitro and deep-tissue antitumor capabilities in vivo compared to that of 808 nm laser. NIR-IIa laser illumination is superior to NIR-I laser for deep-tissue PTT, and shows high potential to improve the PTT outcome.

scholarly journals Spatiotemporal depletion of tumor-associated immune checkpoint PD-L1 with near-infrared photoimmunotherapy promotes antitumor immunity

2021 ◽  
Vol 9 (11) ◽  
pp. e003036
Author(s):  
Shunichi Taki ◽  
Kohei Matsuoka ◽  
Yuko Nishinaga ◽  
Kazuomi Takahashi ◽  
Hirotoshi Yasui ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Immune Checkpoint ◽  
Antitumor Immunity ◽  
Near Infrared ◽  
Specific Antigen ◽  
Cancer Therapeutics ◽  
Antitumor Effects ◽  
Nir Light

BackgroundNear-infrared photoimmunotherapy (NIR-PIT) is a new modality for treating cancer, which uses antibody-photoabsorber (IRDye700DX) conjugates that specifically bind to target tumor cells. This conjugate is then photoactivated by NIR light, inducing rapid necrotic cell death. NIR-PIT needs a highly expressed targeting antigen on the cells because of its reliance on antibodies. However, using antibodies limits this useful technology to only those patients whose tumors express high levels of a specific antigen. Thus, to propose an alternative strategy, we modified this phototechnology to augment the anticancer immune system by targeting the almost low-expressed immune checkpoint molecules on tumor cells.MethodsWe used programmed death-ligand 1 (PD-L1), an immune checkpoint molecule, as the target for NIR-PIT. Although the expression of PD-L1 on tumor cells is usually low, PD-L1 is almost expressed on tumor cells. Intratumoral depletion with PD-L1-targeted NIR-PIT was tested in mouse syngeneic tumor models.ResultsAlthough PD-L1-targeted NIR-PIT showed limited effect on tumor cells in vitro, the therapy induced sufficient antitumor effects in vivo, which were thought to be mediated by the ‘photoimmuno’ effect and antitumor immunity augmentation. Moreover, PD-L1-targeted NIR-PIT induced antitumor effect on non-NIR light-irradiated tumors.ConclusionsLocal PD-L1-targeted NIR-PIT enhanced the antitumor immune reaction through a direct photonecrotic effect, thereby providing an alternative approach to targeted cancer immunotherapy and expanding the scope of cancer therapeutics.

scholarly journals Curcumin Inhibits Tumor Growth and Angiogenesis in an Orthotopic Mouse Model of Human Pancreatic Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Sabrina Bimonte ◽  
Antonio Barbieri ◽  
Giuseppe Palma ◽  
Antonio Luciano ◽  
Domenica Rea ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Cell Signalling ◽  
Malignant Neoplasm ◽  
Human Pancreatic Cancer ◽  
Antitumor Effects ◽  
Orthotopic Mouse Model ◽  
Toxic Agents

Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The best chemotherapeutic agent used to treat pancreatic cancer is the gemcitabine. However, gemcitabine treatment is associated with many side effects. Thus novel strategies involving less toxic agents for treatment of pancreatic cancer are necessary. Curcumin is one such agent that inhibits the proliferation and angiogenesis of a wide variety of tumor cells, through the modulation of many cell signalling pathways. In this study, we investigated whether curcumin plays antitumor effects in MIA PaCa-2 cells.In vitrostudies showed that curcumin inhibits the proliferation and enhances apoptosis of MIA PaCa-2 cells. To test whether the antitumor activity of curcumin is also observedin vivo, we generated an orthotopic mouse model of pancreatic cancer by injection of MIA PaCa-2 cells in nude mice. We placed mice on diet containing curcumin at 0.6% for 6 weeks. In these treated mice tumors were smaller with respect to controls and showed a downregulation of the transcription nuclear factor NF-κB and NF-κB-regulated gene products. Overall, our data indicate that curcumin has a great potential in treatment of human pancreatic cancer through the modulation of NF-κB pathway.

scholarly journals Near-infrared upconversion–activated CRISPR-Cas9 system: A remote-controlled gene editing platform

2019 ◽  
Vol 5 (4) ◽  
pp. eaav7199 ◽  
Author(s):  
Yongchun Pan ◽  
Jingjing Yang ◽  
Xiaowei Luan ◽  
Xinli Liu ◽  
Xueqing Li ◽  
...  
Keyword(s):  
Gene Editing ◽  
Near Infrared ◽  
Cancer Therapeutics ◽  
Guide Rna ◽  
System A ◽  
Nir Light ◽  
Targeted Gene Editing ◽  
Daunting Challenge

As an RNA-guided nuclease, CRISPR-Cas9 offers facile and promising solutions to mediate genome modification with respect to versatility and high precision. However, spatiotemporal manipulation of CRISPR-Cas9 delivery remains a daunting challenge for robust effectuation of gene editing both in vitro and in vivo. Here, we designed a near-infrared (NIR) light–responsive nanocarrier of CRISPR-Cas9 for cancer therapeutics based on upconversion nanoparticles (UCNPs). The UCNPs served as “nanotransducers” that can convert NIR light (980 nm) into local ultraviolet light for the cleavage of photosensitive molecules, thereby resulting in on-demand release of CRISPR-Cas9. In addition, by preparing a single guide RNA targeting a tumor gene (polo-like kinase-1), our strategies have successfully inhibited the proliferation of tumor cell via NIR light–activated gene editing both in vitro and in vivo. Overall, this exogenously controlled method presents enormous potential for targeted gene editing in deep tissues and treatment of a myriad of diseases.

CuS–Pt(iv)–PEG–FA nanoparticles for targeted photothermal and chemotherapy

2016 ◽  
Vol 4 (35) ◽  
pp. 5938-5946 ◽  
Author(s):  
Huiting Bi ◽  
Yunlu Dai ◽  
Jiating Xu ◽  
Ruichan Lv ◽  
Fei He ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Near Infrared ◽  
Drug Induced ◽  
Nir Light

CuS–Pt(iv) nanoparticles exhibited high in vitro and in vivo anti-tumor efficiency, which was caused by the integrated Pt drug-induced chemotherapy and CuS nanoparticle-mediated photothermal therapy (PTT) upon irradiation with near infrared (NIR) light.

scholarly journals Inhibition of SETMAR–H3K36me2–NHEJ repair axis in residual disease cells prevents glioblastoma recurrence

2020 ◽  
Vol 22 (12) ◽  
pp. 1785-1796
Author(s):  
Ekjot Kaur ◽  
Jyothi Nair ◽  
Atanu Ghorai ◽  
Saket V Mishra ◽  
Anagha Achareker ◽  
...  
Keyword(s):  
Mouse Model ◽  
Residual Disease ◽  
Fusion Gene ◽  
Molecular Signaling ◽  
End Joining ◽  
Orthotopic Mouse Model ◽  
Nhej Pathway ◽  
Nhej Repair

Abstract Background Residual disease of glioblastoma (GBM) causes recurrence. However, targeting residual cells has failed, due to their inaccessibility and our lack of understanding of their survival mechanisms to radiation therapy. Here we deciphered a residual cell–specific survival mechanism essential for GBM relapse. Methods Therapy resistant residual (RR) cells were captured from primary patient samples and cell line models mimicking clinical scenario of radiation resistance. Molecular signaling of resistance in RR cells was identified using RNA sequencing, genetic and pharmacological perturbations, overexpression systems, and molecular and biochemical assays. Findings were validated in patient samples and an orthotopic mouse model. Results RR cells form more aggressive tumors than the parental cells in an orthotopic mouse model. Upon radiation-induced damage, RR cells preferentially activated a nonhomologous end joining (NHEJ) repair pathway, upregulating Ku80 and Artemis while downregulating meiotic recombination 11 (Mre11) at protein but not RNA levels. Mechanistically, RR cells upregulate the Su(var)3-9/enhancer-of-zeste/trithorax (SET) domain and mariner transposase fusion gene (SETMAR), mediating high levels of H3K36me2 and global euchromatization. High H3K36me2 leads to efficiently recruiting NHEJ proteins. Conditional knockdown of SETMAR in RR cells induced irreversible senescence partly mediated by reduced H3K36me2. RR cells expressing mutant H3K36A could not retain Ku80 at double-strand breaks, thus compromising NHEJ repair, leading to apoptosis and abrogation of tumorigenicity in vitro and in vivo. Pharmacological inhibition of the NHEJ pathway phenocopied H3K36 mutation effect, confirming dependency of RR cells on the NHEJ pathway for their survival. Conclusions We demonstrate that the SETMAR-NHEJ regulatory axis is essential for the survival of clinically relevant radiation RR cells, abrogation of which prevents recurrence in GBM.

scholarly journals Development of CIDEA reporter mouse model and its application for screening thermogenic drugs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeonho Son ◽  
Cheoljun Choi ◽  
Cheol Song ◽  
Hyeonyeong Im ◽  
Yoon Keun Cho ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mouse Model ◽  
Luciferase Activity ◽  
Reporter System ◽  
Drug Induced ◽  
Reporter Mouse ◽  
Protein Levels ◽  
Beige Adipocytes

AbstractCell death-inducing DNA fragmentation factor-like effector A (CIDEA) is a lipid droplet-associated protein and is a known marker of the thermogenic capacity of brown/beige adipocytes. To monitor the expression of CIDEA in live mice in a non-invasive manner, we generated CIDEA reporter mice expressing multicistronic mRNAs encoding CIDEA, luciferase 2, and tdTomato proteins under the control of the Cidea promoter. The expression level of endogenous CIDEA protein in adipose tissue was not affected by the expression of polycistronic reporters. The two CIDEA reporters, luciferase 2 and tdTomato, correctly reflected CIDEA protein levels. Importantly, luciferase activity was induced by cold exposure and the treatment with β3-adrenergic receptor agonist CL316,243 in interscapular and inguinal adipose tissue, which was detectable by in vivo bioluminescence imaging. We further evaluated the effects of candidate brown adipogenic agents using this CIDEA reporter system and demonstrated a positive correlation between drug-induced luciferase activity and thermogenic gene expression levels both in vitro and in vivo. Collectively, we established a dual CIDEA reporter mouse model in which fluorescence and luminescence signals correctly reflect CIDEA expression, and therefore, suggested that this reporter system can be used to evaluate the thermogenic efficacy of candidate molecules.

Near-Infrared Light Enhanced Peroxidase-Like Activity of PEGylated Palladium Nanozyme for Highly Efficient Biofilm Eradication

2021 ◽  
Vol 17 (6) ◽  
pp. 1131-1147
Author(s):  
Sijin Xiang ◽  
Zhongxiong Fan ◽  
Duo Sun ◽  
Tianbao Zhu ◽  
Jiang Ming ◽  
...  
Keyword(s):  
Infection Control ◽  
Near Infrared ◽  
Antimicrobial Agents ◽  
Infrared Light ◽  
Photothermal Effect ◽  
Highly Efficient ◽  
Nir Light ◽  
Biofilm Infection

The overall eradication of biofilm-mode growing bacteria holds significant key to the answer of a series of infection-related health problems. However, the extracellular matrix of bacteria biofilms disables the traditional antimicrobials and, more unfortunately, hampers the development of the anti-infectious alternatives. Therefore, highly effective antimicrobial agents are an urgent need for biofilm-infection control. Herein, a PEGylated palladium nanozyme (Pd-PEG) with peroxidase (POD)-like activity for highly efficient biofilm infection control is reported. Pd-PEG also shows the intrinsic photothermal effect as well as near-infrared (NIR) light-enhanced POD-like activity in the acidic environment, thereby massively destroying the biofilm matrix and killing the adhering bacteria. Importantly, the antimicrobial mechanism of the synergistic treatment based on Pd-PEG+H2O2+NIR combination was disclosed. In vitro and in vivo results illustrated the designed Pd-PEG+H2O2 +NIR treatment reagent possessed outstanding antibacterial and biofilms elimination effects with negligible biotoxicity. This work hopefully facilitates the development of metal-based nanozymes in biofilm related infectious diseases.

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