GMP-grade nanoparticle targeted to nucleolin downregulates tumor molecular signature, blocking growth and invasion, at low systemic exposure

The Enhanced Efficacy of Intracellular Delivery of Doxorubicin/C6-Ceramide Combination Mediated by the F3 Peptide/Nucleolin System Is Supported by the Downregulation of the PI3K/Akt Pathway

“…Nucleolin tumor overexpression has been demonstrated in tumors of diverse histological origin, including in patient-derived samples, as in breast cancer [ 21 ] and lung cancer [ 25 ]. Gains on therapeutic efficacy, in vivo, arising from nucleolin overexpression has been further evidenced, for example, in pancreatic cancer [ 42 ] or mesothelioma [ 28 ]. In respect to the latter, our group has unraveled nucleolin as an accessible tumor-associated marker for drug delivery into solid tumors, upon intravenous administration of pegylated pH-sensitive liposomes functionalized with the nucleolin-binding F3 peptide.…”

“…In respect to the latter, our group has unraveled nucleolin as an accessible tumor-associated marker for drug delivery into solid tumors, upon intravenous administration of pegylated pH-sensitive liposomes functionalized with the nucleolin-binding F3 peptide. A significant tumor growth inhibition of orthotopic mesothelioma tumors was observed, paralleled by an impairment of the nucleolin-positive vasculature and downregulation of typically overexpressed genes in patients [ 28 ].…”

“…In fact, the presence of nucleolin was verified on the cell surface of human lung cancer cell lines and in the cell membrane of human pulmonary carcinoma tissues [ 25 ], as well as on the surface of breast cancer stem cells, non-stem breast cancer cells and endothelial cells from tumor blood vessels, rendering it as an important target in cancer therapy in the context of solid tumors [ 20 , 26 , 27 ]. Targeted nanomedicine-based approaches aiming at simultaneous spatial and temporal delivery of synergistic drug combinations tackling multiple cellular populations could be highly relevant, providing the accessibility to the CSC niche [ 20 , 28 ].…”

The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

“…Appropriate melanoma animal models are extensively used to assess the biological relevance of therapeutic targets, to evaluate tumor response to therapy, to determine pharmacodynamic and pharmacokinetic profiles, to define the maximum tolerated and firstin-human doses, as well as to identify potential disease progression biomarkers [73,181,182]. The use of animals in preclinical research provides similar complex biological interactions and physiological features to those observed in humans, which is of major importance when studying a multifactorial disease such as cancer [73,183]. Depending on the research purpose, different animal models are available.…”

Multifunctional Nanosystems with Enhanced Cellular Uptake for Tumor Therapy

“…[177] Using the PSMA aptamer, Farokhzad et al developed nanoparticle-aptamer bioconjugates for targeted drug delivery. [178] Through this strategy, aptamers have been employed for various disease-related biomarkers, such as nucleolin, [179] vascular endothelial growth factor, [180] nuclear factor-𝜅B, [181] epidermal growth factor receptor, [182] programmed death-ligand 1, [183] and interleukin 6 receptor. [184] These results indicate that aptamer-based targeting can enhance chemotherapy by increasing the uptake of drug-loaded nanoparticles in target cancer cells.…”