Factors affecting toxicity and efficacy of polymeric nanomedicines

Igarashi, Eiki

doi:10.1016/j.taap.2008.02.007

Cited by 77 publications

(56 citation statements)

References 40 publications

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“…Hence, the increasing applications of nanoparticles in various fields may lead to an increase in human exposure which in turn may increase direct toxicological effects. Despite apparent advantages of certain nanoparticles and their applications, many undesirable side effects of nano-sized particles have been documented in previous studies over the last decade [12,13].…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity and Cytotoxicity of Zinc Oxide and Titanium Dioxide in HEp-2 Cells

et al. 2010

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Aims: The rapidly growing industrial and medical use of nanomaterials, especially zinc oxide and titanium dioxide, has led to growing concerns about their toxicity. Accordingly, the intrinsic genotoxic and cytotoxic potential of these nanoparticles have been evaluated. Materials & methods: Using a HEp-2 cell line, cytotoxicity was tested along with mitochondrial activity and neutral red uptake assays. The genotoxic potential was determined using the Comet and the cytokinesis-blocked micronucleus assays. In addition, tyrosine phosphorylation events were investigated. Results & conclusion: We found concentration- and time-dependent cytotoxicity and an increase in DNA and cytogenetic damage with increasing nanoparticle concentrations. Mainly for zinc oxide, genotoxicity was clearly associated with an increase in tyrosine phosphorylation. Our results suggest that both types of nanoparticles can be genotoxic over a range of concentrations without being cytotoxic.

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Section: Introductionmentioning

confidence: 99%

Genotoxicity and Cytotoxicity of Zinc Oxide and Titanium Dioxide in HEp-2 Cells

et al. 2010

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“…8 Resolving the problem will significantly improve the bioavailability of targeted nanodrugs, enhancing the delivery of the drug to the targeted lesion site, thus improving its therapeutic effect and reducing side effects. 3,9 The surface modification of NPs by polyethylene glycol (PEG) was developed as the first strategy to prolong NP circulation. While PEGylation has helped prolong particle circulation time, it has several limitations, including the transient nature of the effect and the compromised particle-target interactions.…”

mentioning

confidence: 99%

Effect of inhibitors of endocytosis and NF-kB signal pathway on folate-conjugated nanoparticle endocytosis by rat Kupffer cells

Tang¹,

Chen²,

Jia³

et al. 2017

IJN

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The regular accumulation of nanoparticles in the liver makes them hepatotoxic and decreases the circulation time, thus reducing their therapeutic effect. Resolving this problem will be significant in improving bioavailability and reducing side effects. In this study, we reduced the phagocytosis of epirubicin (EPI)-loaded folic acid-conjugated pullulan acetate (FPA/EPI) nanoparticles by Kupffer cells (KCs) through internalization and nuclear factor kappa B (NF-kB) signal pathway inhibitors, thus allowing development of FPA/EPI nanoparticles as a nanodrug delivery system (NDDS) based on our previous study. FPA/EPI nanoparticles were prepared by the dialysis method. Rat KCs were preincubated with the following individual or compound inhibitors: chlorpromazine (CPZ), nystatin (NY), colchicine (Col), amiloride (AMR), and pyrrolidine dithiocarbamate (PDTC). Dose- and time-dependent cellular uptake effects of inhibitors on FPA/EPI nanoparticles were determined through fluorometry. The cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were tested in culture supernatants by bead-based multiplex flow cytometry. The uptake study demonstrated that inhibitors had an obvious inhibitory effect ( P <0.05 or P <0.01), with NY, AMR and Col all showing time-dependent inhibitory effects. PDTC + NY had the strongest inhibitory effect, with an uptake rate of 14.62%. The levels of the three proinflammatory cytokines were changed significantly by the compound inhibitors. TNF-α was significantly inhibited ( P <0.05 or P <0.01), but IL-1β and IL-6 showed smaller decreases. These results suggested that clathrin- and caveolae-mediated endocytosis were the main routes via which nanoparticles entered KCs and that the NF-kB signal pathway was very important too. In summary, multiple mechanisms, including clathrin- and caveolae-mediated endocytosis, contribute to cytokine production in macrophages following exposure to folic acid-conjugated pullulan acetate nanoparticles. Thus, the endocytosis inhibition strategy has great potential for improving therapy and reducing toxicity of an NDDS in the treatment of cancer.

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“…Суттєвою перевагою полімерних носіїв є знижен-ня загальної токсичності ліків та оптимізація фармакокінетичних параметрів їхньої дії [2,3].…”

Section: вступunclassified

Evaluation of cytotoxic and mutagenic action of novel surface active comb-like polyampholytes that are used for delivery of nucleic acids to target cells

et al. 2013

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Створення нових наноматеріалів і бурхливий розвиток нанотехнологій зумов-люють не лише значні досягнення у сфері медицини, у різних галузях промисло-вості й точних технологій, але й небажані наслідки для здоров'я людини і навко-лишнього середовища. Нами досліджено токсичність за умов in vitro і мутагенну активність новосинтезованих поліамфолітних носіїв типу БГ-2, які плануються для використання як носії нуклеїнових кислот у клітини-мішені. Встановлено, що полі-амфолітні носії з ряду БГ-2 у концентрації менше 0,01% не чинять цитотоксичного впливу на клітини ссавців. Не виявлено також їхньої здатності індукувати генні мутації у тесті Еймса. За відсутності метаболічної активації в клітинах-мішенях до-сліджувані носії не мали генотоксичного впливу. Додавання мікросомальної фрак-ції печінки щура не супроводжувалося мутагенним ефектом носіїв щодо штамів ТА98 і ТА100 Salmonella typhimurium. Це свідчить про безпечність використання новосинтезованих поліамфолітних носіїв із ряду БГ-2 як засобів для доставки ну-клеїнових кислот у клітини-мішені.Ключові слова: поліамфолітні носії нуклеїнових кислот, цитотоксичність, мутагенність, тест Еймса. ВСТУПНаноматеріали і нанотехнології все ширше впроваджуються у різні сфери ді-яльності людини. Наноматеріали мають велике біомедичне значення, зокрема у фармакології та хіміотерапії. Наночастинки є основою засобів адресної доставки лікарських засобів, а також виявлення молекулярних біомаркерів у сучасній діа-гностиці [4,5].

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Factors affecting toxicity and efficacy of polymeric nanomedicines

Cited by 77 publications

References 40 publications

Genotoxicity and Cytotoxicity of Zinc Oxide and Titanium Dioxide in HEp-2 Cells

Genotoxicity and Cytotoxicity of Zinc Oxide and Titanium Dioxide in HEp-2 Cells

Effect of inhibitors of endocytosis and NF-kB signal pathway on folate-conjugated nanoparticle endocytosis by rat Kupffer cells

Evaluation of cytotoxic and mutagenic action of novel surface active comb-like polyampholytes that are used for delivery of nucleic acids to target cells

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