Dual Function Antibody Conjugates for Multimodal Imaging and Photoimmunotherapy of Cancer Cells

2021 ◽  
Author(s):  
Mohammad A. Saad ◽  
Marvin Xavierselvan ◽  
Hamza A. Sharif ◽  
Scott Selfridge ◽  
Robert Pawle ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Multimodal Imaging ◽  
Dual Function ◽  
Antibody Conjugates

Imaging and Inhibiting: A Dual Function Molecular Flare for Cancer Cells

2019 ◽  
Vol 91 (21) ◽  
pp. 13501-13507 ◽  
Author(s):  
Shuangzhe Zhang ◽  
Miao Li ◽  
Wenxi Xia ◽  
Jiangli Fan ◽  
Jingyun Wang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Dual Function

Nitric oxide-releasing platinum(iv) prodrug efficiently inhibits proliferation and metastasis of cancer cells

2020 ◽  
Vol 56 (90) ◽  
pp. 14051-14054
Author(s):  
Yi Dai ◽  
Yang Zhu ◽  
Junjie Cheng ◽  
Juan Shen ◽  
Hai Huang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Tumor Metastasis ◽  
Dual Function ◽  
Signaling Molecule ◽  
Proliferation And Metastasis ◽  
Induce Cell Apoptosis ◽  
Nitric Oxide Releasing ◽  
Inhibit Tumor Metastasis

Pt–furoxan, a nitric oxide-releasing platinum(iv) prodrug, exhibits a dual function by releasing cytotoxic cisplatin to induce cell apoptosis, and signaling molecule NO to inhibit tumor metastasis.

scholarly journals Parsing β-catenin’s cell adhesion and Wnt signaling functions in malignant mammary tumor progression

2021 ◽  
Vol 118 (34) ◽  
pp. e2020227118
Author(s):  
David Buechel ◽  
Nami Sugiyama ◽  
Natalia Rubinstein ◽  
Meera Saxena ◽  
Ravi K. R. Kalathur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Wnt Signaling ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Dual Function ◽  
Mammary Tumor Cells ◽  
Cell Cell

During malignant progression, epithelial cancer cells dissolve their cell–cell adhesion and gain invasive features. By virtue of its dual function, β-catenin contributes to cadherin-mediated cell–cell adhesion, and it determines the transcriptional output of Wnt signaling: via its N terminus, it recruits the signaling coactivators Bcl9 and Pygopus, and via the C terminus, it interacts with the general transcriptional machinery. This duality confounds the simple loss-of-function analysis of Wnt signaling in cancer progression. In many cancer types including breast cancer, the functional contribution of β-catenin’s transcriptional activities, as compared to its adhesion functions, to tumor progression has remained elusive. Employing the mouse mammary tumor virus (MMTV)–PyMT mouse model of metastatic breast cancer, we compared the complete elimination of β-catenin with the specific ablation of its signaling outputs in mammary tumor cells. Notably, the complete lack of β-catenin resulted in massive apoptosis of mammary tumor cells. In contrast, the loss of β-catenin’s transcriptional activity resulted in a reduction of primary tumor growth, tumor invasion, and metastasis formation in vivo. These phenotypic changes were reflected by stalled cell cycle progression and diminished epithelial–mesenchymal transition (EMT) and cell migration of breast cancer cells in vitro. Transcriptome analysis revealed subsets of genes which were specifically regulated by β-catenin’s transcriptional activities upon stimulation with Wnt3a or during TGF-β–induced EMT. Our results uncouple the signaling from the adhesion function of β-catenin and underline the importance of Wnt/β-catenin–dependent transcription in malignant tumor progression of breast cancer.

scholarly journals Dual-Function Anti-CD47mAbs Induce Tumor Cell Death and Promote Phagocytosis Resulting in Enhanced in Vivo Efficacy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 991-991
Author(s):  
Pamela T. Manning ◽  
Benjamin J. Capoccia ◽  
Michael P. Rettig ◽  
Ronald R. Hiebsch ◽  
Robert W. Karr ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Tumor Burden ◽  
Dual Function ◽  
Employment Equity ◽  
Hematologic Cancer ◽  
Equity Ownership

Abstract Recent success in immunomodulation of cancer has targeted immune checkpoints such as CTLA-4, PD-1 and PDL-1 to enhance adaptive immunity by stimulating production of tumor-selective, cytotoxic T cells. Anti-CD47mAbs enhance innate immunity by increasing the phagocytosis of tumor cells by macrophages leading to processing and presentation of tumor antigens to prime the adaptive T cell response. Many cancers, including hematologic cancers, up-regulate the expression of CD47 presumably to avoid immune destruction. Increased CD47 expression protects cancer cells from phagocytosis by sending a “don't eat me” signal to macrophages via SIRPalpha, an inhibitory receptor that prevents phagocytosis of CD47-bearing cells. CD47mAbs that block the CD47/SIRPalpha interaction (“blocking-only” mAbs) enhance phagocytosis of cancer cells in vitro. We have identified two CD47mAbs, Vx-1000 and Vx-1004, both of which block the CD47/SIRPalpha interaction and promote phagocytosis of tumor cells by macrophages equally well. However, Vx-1004 also has the unique property of killing cancer cells, but not normal blood cells, via a direct, cell-autonomous, cytotoxic mechanism. Therefore, Vx-1004 is a dual-function antibody. Vx-1004 selectively kills a variety of hematologic cancer cells in vitro, while Vx-1000, the blocking-only mAb, does not as assessed by annexin V staining and flow cytometry (Figure 1). In dose-response studies, cell death in leukemia cells was induced in 2 hrs by <1 ug="" vx-1004="" whereas="" normal="" peripheral="" blood="" mononuclear="" cells="" are="" resistant="" to="" the="" induction="" of="" cell="" death="" by="" following="" incubation="" with="" 10="" for="" 24="" hrs="" both="" these="" cd47mabs="" bind="" many="" species="" cd47="" including="" mouse="" and="" human="" p=""> To determine if the tumor-toxic activity of Vx-1004 confers enhanced efficacy in vivo compared to Vx-1000, we compared them in two mouse hematologic cancer models: murine acute promyelocytic leukemia (APL) and B cell lymphoma (BCL). Briefly, 1x106 GFP-labeled C57BL/6 APL cells were injected IV into wild-type C57BL/6 mice that were then treated IP with 0.4 mg/kg of either Vx-1000 or Vx-1004 on the day of tumor injection and on days 3 and 6 following tumor injection, a very low dose and limited dosing regimen. On day 25, the blood of these mice was analyzed for the number of circulating APL cells. As shown in Figure 2, Vx-1000 did not significantly reduce tumor burden compared to the control group. In contrast, Vx-1004 significantly reduced tumor burden compared to controls, demonstrating greater efficacy of the dual-function CD47mAb. In addition, enhanced efficacy of Vx-1004 compared to Vx-1000 was demonstrated in BCL (Figure 3). In this model, NSG mice were injected with 1x106 murine A20 lymphoma cells subcutaneously and then treated with 0.4mg/kg/day of the CD47mAbs IP for the first five days following tumor injection. In this model, Vx-1000 also failed to inhibit tumor growth compared to controls while Vx-1004 significantly reduced tumor burden at 35 days compared to both the control and Vx-1000 groups, nearly four weeks after treatment was stopped. These data demonstrate increased anti-cancer efficacy with a dual-function CD47mAb that not only blocks the CD47/SIRPalpha interaction to increase phagocytosis of cancer cells, but also selectively kills cancer cells. These studies indicate that dual-function CD47mAbs may have better anti-tumor activity in vivo and support their use in human clinical trials. Figure 1 Figure 1. Disclosures Manning: Corvus Pharmaceutical: Employment, Equity Ownership. Capoccia:Corvus Pharmaceutical: Employment, Equity Ownership. Hiebsch:Corvus Pharmaceutical: Employment, Equity Ownership. Karr:Corvus Pharmaceutical: Employment, Equity Ownership. Frazier:Corvus Pharmaceutical: Consultancy, Equity Ownership.

scholarly journals A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Pengcheng Xu ◽  
Ru Wang ◽  
Wenqian Yang ◽  
Yanyan Liu ◽  
Dongsheng He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Multimodal Imaging ◽  
Breast Cancer Cells ◽  
M2 Macrophage ◽  
Tumour Targeting ◽  
Porous Gold

Abstract Background Although many treatments for breast cancer are available, poor tumour targeting limits the effectiveness of most approaches. Consequently, it is difficult to achieve satisfactory results with monotherapies. The lack of accurate diagnostic and monitoring methods also limit the benefits of cancer treatment. The aim of this study was to design a nanocarrier comprising porous gold nanoshells (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER), a therapeutic monoclonal antibody that binds specifically to human epidermal receptor-2 (HER2)-overexpressing breast cancer cells. Furthermore, a derivative of the microtubule-targeting drug maytansine (DM1) was incorporated in the PGNSs. Methods Prepared PGNSs were coated with mPEG, DM1 and HER via electrostatic interactions and Au–S bonds to yield DM1-mPEG/HER-PGNSs. SK-BR-3 (high HER2 expression) and MCF-7 (low HER2) breast cancer cells were treated with DM1-mPEG/HER-PGNSs, and cytotoxicity was evaluated in terms of cell viability and apoptosis. The selective uptake of the coated PGNSs by cancer cells and subsequent intracellular accumulation were studied in vitro and in vivo using inductively coupled plasma mass spectrometry and fluorescence imaging. The multimodal imaging feasibility and synergistic chemo-photothermal therapeutic efficacy of the DM1-mPEG/HER-PGNSs were investigated in breast cancer tumour-bearing mice. The molecular mechanisms associated with the anti-tumour therapeutic use of the nanoparticles were also elucidated. Result The prepared DM1-mPEG/HER-PGNSs had a size of 78.6 nm and displayed excellent colloidal stability, photothermal conversion ability and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs enhanced the performance of multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumour cell apoptosis via the activation of tubulin, caspase-3 and the heat shock protein 70 pathway. M2 macrophage suppression and anti-metastatic functions were also observed. Conclusion The prepared DM1-mPEG/HER-PGNSs enabled nanodart-like tumour targeting, visibility by CT, PA and PT imaging in vivo and powerful tumour inhibition mediated by chemo-thermal combination therapy in vivo. In summary, these unique gold nanocarriers appear to have good potential as theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted anti-tumour drug delivery system to achieve precision nanomedicine for cancers.

scholarly journals Externalized Keratin 8: A Target at the Interface of Microenvironment and Intracellular Signaling in Colorectal Cancer Cells

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 452 ◽  
Author(s):  
Marie Albaret ◽  
Claudine Vermot-Desroches ◽  
Arnaud Paré ◽  
Jean-Xavier Roca-Martinez ◽  
Lucie Malet ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Intracellular Signaling ◽  
Cancer Biology ◽  
Membrane Surface ◽  
Dual Function ◽  
Kras Mutations ◽  
Colorectal Tumorigenesis ◽  
Colorectal Cancer Cells ◽  
Promising Source

Accumulating evidence supports the remarkable presence at the membrane surface of cancer cells of proteins, which are normally expressed in the intracellular compartment. Although these proteins, referred to as externalized proteins, represent a highly promising source of accessible and druggable targets for cancer therapy, the mechanisms via which they impact cancer biology remain largely unexplored. The aim of this study was to expose an externalized form of cytokeratin 8 (eK8) as a key player of colorectal tumorigenesis and characterize its mode of action. To achieve this, we generated a unique antagonist monoclonal antibody (D-A10 MAb) targeting an eight-amino-acid-long domain of eK8, which enabled us to ascertain the pro-tumoral activity of eK8 in both KRAS-mutant and wild-type colorectal cancers (CRC). We showed that this pro-tumoral activity involves a bidirectional eK8-dependent control of caspase-mediated apoptosis in vivo and of the plasminogen-induced invasion process in cellulo. Furthermore, we demonstrated that eK8 is anchored at the plasma membrane supporting this dual function. We, therefore, identified eK8 as an innovative therapeutic target in CRC and provided a unique MAb targeting eK8 that displays anti-neoplastic activities that could be useful to treat CRC, including those harboring KRAS mutations.

A polydopamine-coated LAPONITE®-stabilized iron oxide nanoplatform for targeted multimodal imaging-guided photothermal cancer therapy

2019 ◽  
Vol 7 (24) ◽  
pp. 3856-3864 ◽  
Author(s):  
Mengxue Liu ◽  
Jiulong Zhang ◽  
Xin Li ◽  
Chao Cai ◽  
Xueyan Cao ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Sialic Acid ◽  
Magnetic Resonance ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Photothermal Therapy ◽  
Multimodal Imaging ◽  
Photoacoustic Imaging

A novel targeted theranostic nanoplatform (LAP–Fe3O4@PDA–PEG–PBA) is constructed for magnetic resonance and photoacoustic imaging-guided photothermal therapy of cancer cells overexpressing sialic acid.

Magnetofluorescent Hybrid Nanoparticles for Phototherapy of Cancer Cells

2009 ◽  
Vol 1189 ◽  
Author(s):  
Dickson K Kirui ◽  
Carl A Batt
Keyword(s):  
Iron Oxide ◽  
Optical Absorption ◽  
Cancer Cells ◽  
Multimodal Imaging ◽  
Hybrid Nanoparticles ◽  
Hybrid Particles ◽  
Specific Targeting ◽  
Fluorescent Molecules

AbstractMagnetofluorescent hybrid nanoparticles consisting of Au layer, an iron oxide moiety, and fluorescent molecules could provide a promising platform for development of multimodal imaging and therapy approaches in the treatment of cancer. However, the feasibility of this platform has yet to be fully explored. In this study, we synthesized biocompatible dumbbell-like iron-gold hybrid particles that are superparamagnetic, fluorescent and with strong optical absorption. Furthermore, we showed that hybrid nanoparticles can be conjugated to targeting agents allowing for specific targeting of cancer cells.

Bio-modified Fe3O4core/Au shell nanoparticles for targeting and multimodal imaging of cancer cells

2012 ◽  
Vol 22 (2) ◽  
pp. 470-477 ◽  
Author(s):  
Ting Zhou ◽  
Baoyan Wu ◽  
Da Xing
Keyword(s):  
Cancer Cells ◽  
Multimodal Imaging ◽  
Shell Nanoparticles

scholarly journals A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy

2020 ◽  
Author(s):  
Yan Shen ◽  
Yuan Ding ◽  
Jiasheng Tu ◽  
Pengcheng Xu ◽  
Wenqian Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Multimodal Imaging ◽  
Electrostatic Interactions ◽  
Cell Uptake ◽  
Gold Nanoshell ◽  
Porous Gold

Abstract BackgroundAlthough many treatments are available for breast cancer, poor tumor targeting limits the effectiveness of most approaches and a monotherapy will yield satisfactory results difficultly. Furthermore, the lack of accurate diagnostic and tumor monitoring methods also limit the benefits of treatment. This study aimed to design a nanocarrier based on porous gold nanoshell (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER) which can specifically bind to human epidermal receptor-2 (Her-2) over-expressed breast cancer cells and was incorporated with a derivative of the microtubule-targeting drug maytansine (DM1). PGNSs were prepared and then covered by the mPEG, DM1 and HER via the electrostatic interactions and Au-S bonds. The cytotoxicity of DM1-mPEG/HER-PGNSs on SK-BR-3 and MCF-7 cancer cells was evaluated in terms of cell viability and apoptosis analysis. The selective cancer cell uptake and accumulation were studied via ICP-MS and fluorescence imaging in vitro and in vivo. The multimodal imaging and synergistic chemo-photothermal therapeutic efficacy was investigated in breast cancer tumor-bearing mice. Then the molecular mechanism of the nanoparticles in anti-tumor applications were also elucidated.ResultThe as-prepared DM1-mPEG/HER-PGNSs with a size of 78.6 nm displayed excellent colloidal stability, photothermal conversion ability, and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs exhibited selectively uptake by cancer cells in vitro and accumulation to tumor sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs showed enhanced multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumor cell apoptosis via the activation of tubulin, caspase-3 and the HSP70 pathway. Meanwhile, the suppression of M2 macrophages and anti-metastatic functions were observed.ConclusionThese DM1-mPEG/HER-PGNSs would display nanodart-like targeting CT/PA/PT imaging in vivo and powerful tumor inhibition mediated by chemo-thermal combination therapy suggest that these unique gold nanocarriers are potential theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted antitumor drug delivery system to achieve precision nanomedicine for cancer.

Sign in / Sign up

Export Citation Format

Share Document