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Normalization of Tumour Blood Vessels Improves the Delivery of Nanomedicines in a Size-Dependent Manner
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Vikash P. Chauhan, Triantafyllos Stylianopoulos, John D. Martin, Zoran Popović, Ou Chen, Walid S. Kamoun, Moungi G. Bawendi, Dai Fukumura, Rakesh K. Jain
To determine how vascular normalization affects nanomedicine delivery, we studied whether the vascular endothelial growth factor (VEGF) receptor-2 blocking antibody DC101 modulates nanoparticle penetration rates in orthotopic mammary tumours in vivo. We used intravital multiphoton microscopy and as probes used a system of quantum dot-based nanoparticles with tunable size and fluorescence emission wavelength but identical surface chemistry [20]. With these tools we measured the effects of DC101 on the real-time delivery of particles ranging from 12 to 125 nm in diameter (the range for approved nanomedicines). Using the resulting data, we applied a novel physiologically based mathematical model for drug delivery to tumours to determine how anti-angiogenics affect pore size distributions. We also used this model to study how pore size distributions can be therapeutically modulated to optimize the delivery of different sizes of nanomedicines.
Drug Targeting: Principles and Applications
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Drug Delivery Approaches and Nanosystems, 2017
Ruslan G. Tuguntaev, Ahmed Shaker Eltahan, Satyajeet S. Salvi, Xing-Jie Liang
It is clear that inflammation associated with neoplastic progression is a complex phenomenon. The microenvironment, which contains a large number of cells and mediators, also are implicated in these inflammatory processes since diverse pathways influence tumor development. Targeting the cancer-associated inflammation certainly will contribute to anticancer therapy generally. Since inflammation is a complex process, agents can be targeted in different pathways. For example, NF-κB activity can be reduced by various compounds, which exert their activity through diverse mechanisms, such as inhibition of IKK$ (NF-κB kinase subunit β), inhibition of proteasomes to disrupt the degradation of IKB or direct targeting of NF-κB-dependent gene expression (Fang et al., 2013). However, sustained NF-κB inhibition can lead to severe side effects caused by immune deficiency (Greten et al., 2007). The IL-6/JAK/STAT3 signaling pathway plays an important role in cancer-associated inflammation (Yu et al.. 2009) and can be disrupted at different levels. Through the demonstrated use of siltuximab, as IL-6 ligand-blocking antibody (Sansone et al., 2012) which can neutralize IL-6, and that ruxolitinib (Verstovsek, 2009) that blocks Janus activated kinase (JAK) phosphorylation of STAT3, tumor-associated inflammation can be significantly reduced. In order to reduce inflammation and its protumoral influence, TNF-α antagonists, such as, monoclonal antibody-infliximab, or fusion protein-etanercept, also have been applied. Moreover, inhibition of tumor-associated macrophages (TAMs) through targeting recruitment factors, including CSF-1, CCL2, or MCP-1, makes this approach potentially useful for the treatment of cancer-associated inflammation (Fang et al., 2013).
Hydrogels and Their Applications in Targeted Drug Delivery
Published in Shaker A. Mousa, Raj Bawa, Gerald F. Audette, The Road from Nanomedicine to Precision Medicine, 2020
Radhika Narayanaswamy, Vladimir P. Torchilin
Injectable hydrogels responsive to Reactive Oxygen Species (ROS) that degrade in the presence of ROS and promote immunogenic tumor phenotype via local gemcitabine delivery is a recent discovery. The PVA cross-linked hydrogel with ROS-labile linkers enhance anti-tumor response with a localized release of immune checkpoint blocking antibody (anti-PD-L1 blocking antibody (aPDL-1)) in in vitro and immunogenic in vivo mice models. Tumor recurrence prevention after primary resection is the therapeutic advantage of this chemo-immunotherapy [63].
A novel gold-polymer-antibody conjugate for targeted (radio-photothermal) treatment of HepG2 cells
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Wael M. Darwish, Noha A. Bayoumi, Hanan M. El-Shershaby, Kamel A. Moustafa
Combination of photothermal and targeted radiotherapy using 177Lu labeled gold nanoparticles-peptide conjugate proved high cytotoxicity against breast cancer cells [10]. In addition, radiolabelling of different gold-antibody conjugate with SPECT or PET imaging radionuclides (111In and 89Zr) enhanced the imaging contrast by increasing both internalization and retention of the radioisotopes in the tumor cells [11]. Atezolizumab (ATZ) is a programmed death-ligand 1 (PD-L1) blocking antibody (or immune checkpoint inhibitor) used in the treatment of hepatocellular carcinoma (HCC) and many other cancer types [12].
Traffic-related particulate matter aggravates ocular allergic inflammation by mediating dendritic cell maturation
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Moonwon Hwang, Sehyun Han, Jeong-Won Seo, Ki-Joon Jeon, Hyun Soo Lee
Single cells from draining LNs were prepared by tissue homogenization followed by filtration through a 70 μm cell strainer and trypan blue exclusion test was used to determine cell viability. Cells were incubated with Fc-receptor blocking antibody in 0.5% BSA at 4°C for 30 min prior to immunostaining with PE-Cy7-conjugated anti-CD11c and APC-Cy7-conjugated anti-I-Ad antibodies. The isotype control was stained with the properly matched antibodies (eBioscience). Stained cells were analyzed with a flow cytometer (BD LSRFortessa, BD Biosciences) and the FlowJo program (Tree Star, Ashland, OR).