Biodistribution of nanoparticles: Initial considerations

Miranda, Lucas; Albernaz, Marta de Souza; Patricio, Beatriz Ferreira de Carvalho; Falcão, Mario Villela; Coelho, Bianca; Bordim, Augusto; Almeida, Julio Cesar; Santos-Oliveira, Ralph

doi:10.1016/j.jpba.2012.06.008

Cited by 37 publications

(17 citation statements)

References 8 publications

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“…The in vivo fate of nanoparticles is governed by their physiological properties such as size, shape, composition, surface chemistry and physical properties [18,19]. The biodistribution profile observed for PVX matches previous reports for nanomaterials of similar size, shape and composition.…”

Section: Resultssupporting

confidence: 71%

“…Spherical nanomaterials 30–80 nm in diameter tend to be sequestered in the lungs and leaky vasculature, whereas those larger than 80 nm are generally trapped in the spleen and liver [20,21]. Nanomaterials similar in size to PVX are not usually excreted by the renal system, but are mainly removed from circulation efficiently by the MPS [18,19,22]. …”

Section: Resultsmentioning

confidence: 99%

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Biodistribution and Clearance of A Filamentous Plant Virus in Healthy and Tumor-Bearing Mice

et al. 2014

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Aim-Nanoparticles based on plant viruses are emerging biomaterials for medical applications such as drug delivery and imaging. Their regular structures can undergo genetic and chemical modifications to carry large payloads of cargos, as well as targeting ligands. Of several such platforms under development, only few have been characterized in vivo. We recently introduced the filamentous plant virus, potato virus X (PVX), as a new platform. PVX presents with a unique nanoarchitecture and is difficult to synthesize chemically.Methods-Here, we present a detailed analysis of PVX biodistribution and clearance in healthy mice and mouse tumor xenograft models using a combination of ex vivo whole-organ imaging, quantitative fluorescence assays and immunofluorescence microscopy.Results & conclusion-While up to 30% of the PVX signal was from the colon, mammary and brain tumor tissues, remaining particles were cleared by the reticuloendothelial system organs (the spleen and liver), followed by slower processing and clearance through the kidneys and bile.Keywords anisotropic nanoparticle; biodistribution; immunogenicity; mononuclear phagocyte system; nanoparticle shape; polyethylene glycol; tumor homing; viral nanoparticle Plant viruses and bacteriophages have been recognized as potentially useful biomaterials for a range of nanomedical applications, including tissue-specific imaging, drug delivery and vaccine development [1]. Viruses are versatile because they are symmetrical, monodisperse protein structures that form icosahedrons, tubes or filaments, which encapsulate nucleic acids and deliver them efficiently to cells. They have evolved robust structures that withstand the adverse conditions present during infection, but remain responsive to subtle physiological parameters, such as pH and temperature, allowing them to disassemble and reassemble for self-propagation. These attributes can be exploited to develop virus-based nanoparticles (VNPs) that are amenable to chemical and genetic modification, allowing the incorporation of drugs, contrast and imaging probes, as well as targeting ligands conjugated to either the external or internal particle surface, or packaged inside through the use of induced disassembly and reassembly strategies [2]. The ease of production by molecular farming in plants makes VNP technology highly scalable. Shukla et al. Page 2 Nanomedicine (Lond). Author manuscript; available in PMC 2014 September 19. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe application and development of plant VNPs is still a relatively young discipline.Although various platforms have been tested and developed in the test tube (e.g., various modification strategies have been devised), only few examples have been characterized in vivo; principally, the icosahedrons cowpea chlorotic mottle virus (CCMV) and cowpea mosaic virus (CPMV) [3,4]. Both plant VNPs demonstrated rapid blood pool clearance and were detected in a wide variety of tissues throughout the body; CPMV accumulated primari...

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Section: Resultssupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Biodistribution and Clearance of A Filamentous Plant Virus in Healthy and Tumor-Bearing Mice

et al. 2014

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“…The nanoparticles accumulation in the liver may be due to reabsorption before it was eliminated by kidney from the system. The absorbance in the kidney may be linked to nanoparticles absorption into the circulation and deposition into the renal tissues [21].…”

Section: Biodistribution Assaysmentioning

confidence: 99%

Biocompatibility and biodistribution of suberoylanilide hydroxamic acid loaded poly (DL-lactide-co-glycolide) nanoparticles for targeted drug delivery in cancer

Sankar

Ravikumar

2014

Biomedicine & Pharmacotherapy

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“…The liver's role in clearance is more prominent when the oligonucleotides are associated with nanoparticles [140]. Clearance by the kidney, on the other hand, has been demonstrated in nanoparticle and non-nanoparticle-based miRNA therapeutics [141]. Studies that characterized the clearance of antisense oligonucleotides were extensively reported during the 1990s [142][143][144].…”

Section: Biodistribution and Renal Clearancementioning

confidence: 99%

MicroRNA and Drug Delivery

Fernandez-Moure

Eps

Weiner

et al. 2014

MicroRNA in Development and in the Progression of Cancer

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The human genome was once thought to be a redundant sequence containing few functional regions coding for proteins. This teaching is being rewritten as we continue to understand the vast complexity of the noncoding regions of the genetic code. These regions we now understand are transcribed into small single-stranded segments or microRNAs (miRNAs) that participate in the regulation of gene expression. miRNAs interact across many pathways and thus have the potential as targets for oncologic therapies. Their efficacy is limited because methods to traverse the many biologic barriers are yet to be developed. In order to achieve effective therapeutic levels at the site of interest, the tumor, the miRNA must be shuttled to the site and simultaneously be protected from the body's defensive mechanisms. To this end, scientists have developed many vehicles for delivery at both the micro-and nanoscale using both synthetic and biologically derived vectors. Viral vectors continue to be the most commonly used vehicles, but are plagued by complications related to the vector itself. These inadequacies led researchers to explore synthetic materials such aspolylactic co-glycolic-acid (PLGA), silicon, gold, and liposomes to overcome the biobarriers of our body. While these vehicles have shown promise, problems such as high clearance rates, poor tumor accumulation and targeting, and adverse reactions have limited their translation into the clinic. In order to overcome these problems, a multistage theory was developed. By decoupling the tasks required of the carrier system, the multistage delivery system is able to simultaneously protect the payload, target the site of interest, and deliver the payload in therapeutic concentrations. This presents a paradigm shift in the concept of drug delivery and may provide the solution to the limited translational gene therapy in oncology.

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Biodistribution of nanoparticles: Initial considerations

Cited by 37 publications

References 8 publications

Biodistribution and Clearance of A Filamentous Plant Virus in Healthy and Tumor-Bearing Mice

Biodistribution and Clearance of A Filamentous Plant Virus in Healthy and Tumor-Bearing Mice

Biocompatibility and biodistribution of suberoylanilide hydroxamic acid loaded poly (DL-lactide-co-glycolide) nanoparticles for targeted drug delivery in cancer

MicroRNA and Drug Delivery

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