Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration

Brown, Anna L.; Kai, Marc P.; DuRoss, Allison N.; Sahay, Gaurav; Sun, Conroy

doi:10.3390/nano8060410

Cited by 34 publications

(27 citation statements)

References 37 publications

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“…The biggest depositions of the studied nanoparticles were observed in the liver and spleen. The test results (AST, ALT, bilirubin, albumin, blood urea nitrogen, creatinine and sodium) showed no abnormal levels in comparison to the control group [27].…”

Section: Intravenous Administrationmentioning

confidence: 66%

Are platinum nanoparticles safe to human health?

Czubacka

Czerczak

2019

Med Pr

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Platinum nanoparticles (PtNPs) have been widely used not only in industry, but above all in medicine and diagnostics. However, there are disturbing reports related to the toxic effects of nanoplatinum, which is the main reason why the authors of this study have decided to review and analyze literature data related to its toxicity and impact on human health. While PtNPs may be absorbed by the respiratory and digestive tract, and can penetrate through the epidermis, there is no evidence concerning their absorption through the skin. Platinum nanoparticles accumulate mainly in the liver and spleen although they also reach other internal organs, such as lungs, kidneys or heart. Toxicokinetics of platinum nanoparticles depends strongly on the particle size. Only few studies regarding platinum nanoparticles toxicity have been conducted. Animals intratracheally exposed to platinum nanoparticles have demonstrated an increased level of proinflammatory cytokines in bronchoalveolar lavage which confirms inflammatory response in the lungs. Oral administration of PtNPs can cause inflammatory response and induce oxidative stress. Nanoplatinum has been found to induce hepatotoxicity and nephrotoxicity via the intravenous route. It can cause DNA damage and cellular apoptosis without significant cytotoxicity. There are no research studies on its carcinogenicity. Fetal or maternal toxicity has not been observed, but an increased mortality and a decreased growth of the offspring have been demonstrated. Platinum nanoparticles may permeate the skin barrier but there is no evidence for their absorption. Due to the insufficient number of tests that have been carried out to date, it is not possible to clearly determine the occupational exposure limit value; however, caution is recommended to employees exposed to their effects.

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Section: Intravenous Administrationmentioning

confidence: 66%

Are platinum nanoparticles safe to human health?

Czubacka

Czerczak

2019

Med Pr

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“…injected nanoparticles immediately after injection. [ 24‐26 ] This accretion continued with time (Figure 1a). Conversely, i.t.…”

Section: Figurementioning

confidence: 89%

Immunostimulatory TLR7 Agonist‐Nanoparticles Together with Checkpoint Blockade for Effective Cancer Immunotherapy

Huang

Mendez

Echeagaray

et al. 2020

Advanced Therapeutics

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Mono‐ or dual‐checkpoint inhibitors for immunotherapy have changed the paradigm of cancer care; however, only a minority of patients responds to such treatment. Combining small molecule immunostimulators can improve treatment efficacy, but they are restricted by poor pharmacokinetics. In this study, conjugated TLR7 agonists onto silica nanoparticles show extended drug localization after intratumoral injection. The nanoparticle‐based TLR7 agonist increases immune stimulation by activating the TLR7 signaling pathway. When treating CT26 colon cancer, nanoparticle conjugated TLR7 agonists increase T cell infiltration into the tumors by >4× and upregulate expression of the interferon γ gene compared to its unconjugated counterpart by ≈2×. Toxicity assays establish that the conjugated TLR7 agonist is a safe agent at the effective dose. When combined with checkpoint inhibitors that target programmed cell death protein 1 (PD‐1) and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4), a 10–100× increase in immune cell migration is observed; furthermore, 100 mm3 tumors are treated, and a 60% remission rate is observed including remission at contralateral noninjected tumors. The data show that nanoparticle‐based TLR7 agonists are safe and can potentiate the effectiveness of checkpoint inhibitors in immunotherapy resistant tumor models and promote a long‐term specific memory immune function.

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“…In a 24 hr in vitro exposure of HepG2 cells to Ag NM (approximately 25 nm), at a concentration range up to 100 µg/ml, the particles produced significant cytotoxicity at concentrations above 5 µg/ml (Braeuning et al 2018). Subsequent elemental analysis of Ag in hepatocytes suggested that only a small fraction of Ag was taken up (or retained) by the cells (8% of administered concentration).…”

Section: Hepatocyte Only Test Modelsmentioning

confidence: 99%

A review of hepatic nanotoxicology – summation of recent findings and considerations for the next generation of study designs

Kermanizadeh

Powell

Stone

2020

Journal of Toxicology and Environmental Health, Part B

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The liver is one of the most important multi-functional organs in the human body. Amongst various crucial functions, it is the main detoxification center and predominantly implicated in the clearance of xenobiotics potentially including particulates that reach this organ. It is now well established that a significant quantity of injected, ingested or inhaled nanomaterials (NMs) translocate from primary exposure sites and accumulate in liver. This review aimed to summarize and discuss the progress made in the field of hepatic nanotoxicology, and crucially highlight knowledge gaps that still exist. Key considerations include The review offers a number of important suggestions for the future of hepatic nanotoxicology study design. This is of great significance as its findings are highly relevant due to the development of more advanced in vitro, and in silico models aiming to improve physiologically relevant toxicological testing strategies and bridging the gap between in vitro and in vivo experimentation.

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Biodistribution and Toxicity of Micellar Platinum Nanoparticles in Mice via Intravenous Administration

Cited by 34 publications

References 37 publications

Are platinum nanoparticles safe to human health?

Are platinum nanoparticles safe to human health?

Immunostimulatory TLR7 Agonist‐Nanoparticles Together with Checkpoint Blockade for Effective Cancer Immunotherapy

A review of hepatic nanotoxicology – summation of recent findings and considerations for the next generation of study designs

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