Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

Capolla, Sara; Garrovo, Chiara; Zorzet, Sonia; Lorenzon, Andrea; Rampazzo, Enrico; Spretz, Ruben; Pozzato, Gabriele; Núñez, Luis; Tripodo, Claudio; Macor, Paolo; Biffi, Stefania

doi:10.2147/ijn.s78995

Cited by 24 publications

(9 citation statements)

References 31 publications

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“…The renal localization of Ergidina cannot be attributed to the clearance of the molecule, because its molecular weight of approximately 120 kDa is well above the size limit of the molecules filtering through the glomeruli under physiologic conditions. The weak fluorescent signal observed in the bladder is due to small amount of free fluorescent dye excreted in the urine (20, 27). A plausible explanation for the preferential homing of the neutralizing anti-C5 antibody to the kidney is that the recombinant molecule interacts with integrins expressing RGD-binding sites.…”

Section: Discussionmentioning

confidence: 99%

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Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

et al. 2017

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Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process. To this end, we generated Ergidina, a neutralizing recombinant anti-C5 human antibody coupled with a cyclic-RGD peptide, with a distinctive homing property for ischemic endothelial cells and effective in controlling tissue damage in a rat model of renal ischemia/reperfusion injury (IRI). As a result of its preferential localization on renal endothelium, the molecule induced complete inhibition of complement activation at tissue level, and local protection from complement-mediated tissue damage without affecting circulating C5. The ex vivo binding of Ergidina to surgically removed kidney exposed to cold ischemia supports its therapeutic use to prevent posttransplant IRI leading to delay of graft function. Moreover, the finding that the ex vivo binding of Ergidina was not restricted to the kidney, but was also seen on ischemic heart, suggests that this RGD-targeted anti-C5 antibody may represent a useful tool to treat organs prior to transplantation. Based on this evidence, we propose preliminary data showing that Ergidina is a novel targeted drug to prevent complement activation on the endothelium of ischemic kidney.

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Section: Discussionmentioning

confidence: 99%

“…A small-animal time-domain Optix MX preclinical NIR-imager (Advanced Research Technologies) equipped with a pulsed laser diode and a time-correlated single photon counting detector was used in this study for the in vivo and ex vivo evaluation of labeled Ergidina distribution, as previously detailed (20). …”

Section: Methodsmentioning

confidence: 99%

Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

et al. 2017

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“…ese kinds of antibodies are made of two different monomers, which, due to a knob into hole mechanism, are able to self-assemble in a scFv-Fc antibody [119]. According to this strategy, a bispecific antibody can be generated, one arm of the molecule with an antigen tissue specificity and the other one able to block an inflammatory cytokine [3] or a protein of the complement system [120].…”

Section: Recombinant Antibodies Andmentioning

confidence: 99%

“…is process can affect the efficacy of NPs to effectively reach their target and exert a therapeutic effect [1], as well as potentially increase the risk of unwanted liver toxicity [2]. Biodistribution studies have demonstrated that the clearance action exerted by the liver is confirmed for the majority of NP designs: polymeric NPs [3][4][5], micelles [6,7], quantum dots [8], gold NPs [9], and carbon nanotubes [10]. In this context, injected nanomaterials usually accumulate in the liver and in an amount that depends on their physiochemical properties, such as size, shape, and surface functionalization, although relatively little is understood about dynamics of NP transport at the intraorgan level [11,12].…”

Section: Introductionmentioning

confidence: 99%

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

Baboci

Capolla

Cintio

et al. 2020

Journal of Oncology

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e development of nanostructures for therapeutic purpose is rapidly growing, following the results obtained in vivo in animal models and in the clinical trials. Unfortunately, the potential therapeutic efficacy is not completely exploited, yet. is is mainly due to the fast clearance of the nanostructures in the body. Nanoparticles and the liver have a unique interaction because the liver represents one of the major barriers for drug delivery. is interaction becomes even more relevant and complex when the drug delivery strategies employing nanostructures are proposed for the therapy of liver diseases, such as hepatocellular carcinoma (HCC). In this case, the selective delivery of therapeutic nanoparticles to the tumor microenvironment collides with the tendency of nanostructures to be quickly eliminated by the organ. e design of a new therapeutic approach based on nanoparticles to treat HCC has to particularly take into consideration passive and active mechanisms to avoid or delay liver elimination and to specifically address cancer cells or the cancer microenvironment. is review will analyze the different aspects concerning the dual role of the liver, both as an organ carrying out a clearance activity for the nanostructures and as target for therapeutic strategies for HCC treatment.

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“…Capolla and colleagues also used an anti-CD20 antibody functionalized into polymeric-fluorophore Cy5.5-labeled NPs for in vivo imaging directed at the diagnosis of B-cell malignancies. These NPs might also be used as a personalized treatment strategy by loading with drugs, becoming an attractive theranostics platform (Table 1 ) (Capolla et al, 2015 ). Besides CD20 antigens, CD45 and CD19 are the two most common surface proteins expressed by B-cells and used in diagnostic immunophenotyping.…”

Section: Nps Applications In Liquid Tumorsmentioning

confidence: 99%

Nanoparticles—Emerging Potential for Managing Leukemia and Lymphoma

Vinhas

Mendes

Fernandes

et al. 2017

Front. Bioeng. Biotechnol.

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Nanotechnology has become a powerful approach to improve the way we diagnose and treat cancer. In particular, nanoparticles (NPs) possess unique features for enhanced sensitivity and selectivity for earlier detection of circulating cancer biomarkers. In vivo, NPs enhance the therapeutic efficacy of anticancer agents when compared with conventional chemotherapy, improving vectorization and delivery, and helping to overcome drug resistance. Nanomedicine has been mostly focused on solid cancers due to take advantage from the enhanced permeability and retention (EPR) effect experienced by tissues in the close vicinity of tumors, which enhance nanomedicine’s accumulation and, consequently, improve efficacy. Nanomedicines for leukemia and lymphoma, where EPR effect is not a factor, are addressed differently from solid tumors. Nevertheless, NPs have provided innovative approaches to simple and non-invasive methodologies for diagnosis and treatment in liquid tumors. In this review, we consider the state of the art on different types of nanoconstructs for the management of liquid tumors, from preclinical studies to clinical trials. We also discuss the advantages of nanoplatforms for theranostics and the central role played by NPs in this combined strategy.

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Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

Cited by 24 publications

References 31 publications

Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

Nanoparticles—Emerging Potential for Managing Leukemia and Lymphoma

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