Anatomical Targeting Improves Delivery of Unconjugated Nanoparticles to the Testicle

Snow-Lisy, Devon C.; Sabanegh, Edmund; Samplaski, Mary K.; Labhasetwar, Vinod

doi:10.1016/j.juro.2015.03.076

Cited by 7 publications

(4 citation statements)

References 26 publications

(23 reference statements)

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“…Recently, FSHR is identified as a universal tumor angiogenesis target, and this receptor has already been used for ovarian cancer targeting both in vitro and in vivo [26, 27]. However, traditional peptide [42, 43] or polypeptide [27] based FSHR ligands usually have unsatisfactory stability and target-binding affinity in vivo . In comparison, FSHR antibody exhibited higher affinity, better resistance to degradation, and simpler conjugation chemistry.…”

Section: Discussionmentioning

confidence: 99%

In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide

et al. 2016

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Angiogenesis, i.e. the formation of neovasculatures, is a critical process during cancer initiation, progression, and metastasis. Targeting of angiogenic markers on the tumor vasculature can result in more efficient delivery of nanomaterials into tumor since no extravasation is required. Herein we demonstrated efficient targeting of breast cancer metastasis in an experimental murine model with nano-graphene oxide (GO), which was conjugated to a monoclonal antibody (mAb) against follicle-stimulating hormone receptor (FSHR). FSHR has been confirmed to be a highly selective tumor vasculature marker, which is abundant in both primary and metastatic tumors. These functionalized GO nano-conjugates had diameters of ~ 120 nm based on atomic force microscopy (AFM), TEM, and dynamic laser scattering (DLS) measurement. 64 Cu was incorporated as a radiolabel which enabled the visualization of these GO conjugates by positron emission tomography (PET) imaging. Breast cancer lung metastasis model was established by intravenous injection of click beetle green luciferase-transfected MDA-MB-231 (denoted as cbgLuc-MDA-MB-231) breast cancer cells into female nude mice and the tumor growth was monitored by bioluminescence imaging (BLI). Systematic in vitro and in vivo studies have been performed to investigate the stability, targeting efficacy and specificity, and tissue distribution of GO conjugates. Flow cytometry and fluorescence microscopy examination confirmed the targeting specificity of FSHR-mAb attached GO conjugates against cellular FSHR. More potent and persistent uptake of 64 Cu-NOTA-GO-FSHR-mAb in cbgLuc-MDA-MB-231 nodules inside the lung was witnessed HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript when compared with that of non-targeted GO conjugates ( 64 Cu-NOTA-GO). Histology evaluation also confirmed the vasculature accumulation of GO-FSHR-mAb conjugates in tumor at early time points while they were non-specifically captured in liver and spleen. In addition, these GO conjugates can serve as good drug carriers with satisfactory drug loading capacity (e.g. for doxorubicin [DOX], 756 mg/g). Enhanced drug delivery efficiency in cbgLuc-MDA-MB-231 metastatic sites was demonstrated in DOX-loaded GO-FSHR-mAb by fluorescence imaging. This FSHR-targeted, GO-based nanoplatform can serve as a useful tool for early metastasis detection and targeted delivery of therapeutics. Graphical Abstract KeywordsNano-graphene oxide (GO); Angiogenesis; Follicle-stimulating hormone receptor (FSHR); Breast cancer metastasis; Positron emission tomography (PET); Image-guided drug delivery

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Section: Discussionmentioning

confidence: 99%

In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide

et al. 2016

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“…However, their particles benefited from either anatomical targeting-injection into the testicular artery-or biochemical targeting with FSH coating of particles. They also did not check for the absence of interference related to testicular autofluorescence [131].…”

Section: Nanoparticles Interfacing With the Blood-testis Barriermentioning

confidence: 99%

Impact of Nanoparticles on Male Fertility: What Do We Really Know? A Systematic Review

Klein

Méry

Boudard

et al. 2022

IJMS

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The real impact of nanoparticles on male fertility is evaluated after a careful analysis of the available literature. The first part reviews animal models to understand the testicular biodistribution and biopersistence of nanoparticles, while the second part evaluates their in vitro and in vivo biotoxicity. Our main findings suggest that nanoparticles are generally able to reach the testicle in small quantities where they persist for several months, regardless of the route of exposure. However, there is not enough evidence that they can cross the blood–testis barrier. Of note, the majority of nanoparticles have low direct toxicity to the testis, but there are indications that some might act as endocrine disruptors. Overall, the impact on spermatogenesis in adults is generally weak and reversible, but exceptions exist and merit increased attention. Finally, we comment on several methodological or analytical biases which have led some studies to exaggerate the reprotoxicity of nanoparticles. In the future, rigorous clinical studies in tandem with mechanistic studies are needed to elucidate the real risk posed by nanoparticles on male fertility.

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“…Blood vessels function as a transportation pipe for blood, which carries nutrients and other necessary substances, such as hormones. Blood is extensively circulated through those vessels and NPs in the blood may reside on the surface of vessels or go through some barriers, e.g., the blood–brain barrier [ 15 ], blood–gas barrier [ 16 ] and blood–testis barrier [ 17 ], and reach important organs which then may get threatened (brain [ 18 – 19 ], lung [ 20 – 21 ] and testis [ 22 ]). In order to reduce possible limitations to the application of NPs, a better understanding of the relationship between the blood vascular system and NPs is very important.…”

Section: Introductionmentioning

confidence: 99%

Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

Zhang

Yang

2016

Beilstein J. Nanotechnol.

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SummarySince nanoparticles are now widely applied as food additives, in cosmetics and other industries, especially in medical therapy and diagnosis, we ask here whether nanoparticles can cause several adverse effects to human health. In this review, based on research on nanotoxicity, we mainly discuss the negative influence of nanoparticles on blood vessels in several aspects and the potential mechanism for nanoparticles to penetrate endothelial layers of blood vessels, which are the sites of phosphorylation of tight junction proteins (claudins, occludins, and ZO (Zonula occludens)) proteins, oxidative stress and shear stress. We propose a connection between the presence of nanoparticles and the regulation of the tight junction, which might be the key approach for nanoparticles to penetrate endothelial layers and then have an impact on other tissues and organs.

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Anatomical Targeting Improves Delivery of Unconjugated Nanoparticles to the Testicle

Abstract: Arterial injection for anatomical targeting of nanoparticles to the testis is feasible, improves unconjugated nanoparticle delivery to testicular tissue and enables nanoparticles to cross the gonadal vascular endothelium and the blood-testis barrier.

Cited by 7 publications

References 26 publications

In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide

In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide

Impact of Nanoparticles on Male Fertility: What Do We Really Know? A Systematic Review

Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

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