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Applications of Liposomal Drug Delivery Systems to Cancer Therapy
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Current understanding of the molecular processes underlying the pathologic behavior of cancer cells has progressed enormously in the last decade.6 Of particular relevance to cancer targeting is the fact that a number of receptors, mostly growth factor receptors, have been found to be overexpressed in tumor cells and to play an important role as catalysts of growth. Receptor profiling of tumors may offer a potential Achilles heel for targeting specific ligands or antibodies with or without delivery of a cytotoxic drug cargo.7 In addition, the pathophysiology of tumor neovasculature and the interaction of tumor with stroma have been recognized as processes that play a major role in tumor development. Cancer is ultimately a disease caused by somatic gene mutations that result in the transformation of a normal cell into a malignant tumor cell. Eventually, the tumor cell phenotype progresses along three major steps:8Increased proliferation rate and/or decreased apoptosis, causing an increase of tumor cell mass.Invasion of surrounding tissues and switch on of angiogenesis. This is a critical step that differentiates in situ, non-invasive tumors with no metastatic potential from invasive tumors with metastatic and life-threatening potential.Metastases, i.e., abnormal migration of tumor cells from the primary tumor site via blood vessels or lymphatics to distant organs with formation of secondary tumors. Most commonly, this is the process that causes death of the host because of disruption of the function of vital organs or systems (brain, lung, liver, kidney, bone marrow, coagulation, intestinal passage, and other).
Gold Nanoparticles in Cancer Therapy
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Li Tian, Linfeng Lu, Marites P. Melancon
Table 2.1 lists the most common ligands and their targets used in cancer therapy [35]. Several ligands have been conjugated on the surface of AuNPs for increased specificity and accumulation into the tumor. Among them are peptides, aptamers, and antibodies targeted to different families of growth factor receptors. In particular, the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein that has 1186 amino acids [36], has been a primary target in nanoparticle research [37]. EGFR has an extracellular ligand-binding domain, a single transmembrane domain, and an intracellular tyrosine kinase-containing domain [38]. Anti-EGFR antibodies have been conjugated to AuNPs [39, 40] by noncovalently binding the antibodies at their isoelectric points with AuNPs [41] or a thiol extension by N-succinimidyl S-acetylthioacetate (SATA) from the amine groups on the antibodies [9]. Melancon et al. functionalized a clinically approved anti-EGFR antibody, cetuximab (C225), with SATA and then conjugated it to hollow gold nanospheres (C225-HAuNS) [9]. EGFR positive A431 cells had higher uptake of C225-HAuNS when compared with the control, non-targeted IgG-HAuNS. The conjugation also enhanced the photothermal ablation efficacy on the A431 cells in vitro and increased accumulation within the tumor in vivo. C225 can also target other multifunctional AuNPs to tumors overexpressing EGFR. For example, superparamagnetic iron oxide coated with gold nanoshell (SPIO@AuNS) functionalized with C225 (C225-SPIO@AuNS) had higher accumulation in the A431 xenograft with enhanced MR signal of the tumor tissue and improved photothermal ablation outcome in vivo [42]. Ligands with different affinities to EGFR may result in different targeting results. The same research group later compared the targeting ability of an aptamer with C225, and found out the aptamer had a superior targeting ability in orthotopic tumor model from a head and neck cancer cell line, OSC-19-Luc [43]. EGFR targeting can also be used to co-deliver other therapeutic agents. For example, Meyers et al. used epidermal growth factor peptide-targeted gold nanoparticles (EGFpep-AuNPs) to deliver Pc4 as a PDT agent [44]. The in vivo results suggested that Pc4 accumulation in rat glioma 9L.E29 cell xenografts of EGFpep-AuNP-Pc 4 group was more than three times higher than that of the untargeted AuNP group.
Natural latex serum: characterization and biocompatibility assessment using Galleria mellonella as an alternative in vivo model
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Giovana Sant’Ana Pegorin Brasil, Patrícia Pimentel de Barros, Matheus Carlos Romeiro Miranda, Natan Roberto de Barros, Juliana Campos Junqueira, Alejandro Gomez, Rondinelli Donizetti Herculano, Ricardo José de Mendonça
The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling system contains 22 members, which are responsible for regulating a variety of biological processes, including embryogenesis, angiogenesis, tissue homeostasis, wound repair and cancer. It has been observed in most studies that different members of the FGF family, mainly FGF1 and FGF2, can induce in vitro a complex pro-angiogenic phenotype in endothelial cells, which covers various aspects of angiogenesis in vivo, including from modulation of cell proliferation, migration, protease production, integrin and cadherin receptor expression, and intercellular gap junction communication [79, 80].