Abstract
Nanomedicines exhibit unbelievable capability in overcoming the hurdles faced in biological applications. Carbon nanotubes (CNTs), graphene-family nanomaterials and fullerenes are a class of engineered nanoparticles that have emerged as a new option for possible use in drug/gene delivery for life-threatening diseases. Their adaptability to pharmaceutical applications has opened new vistas for biomedical applications. Successful applications of this family of engineered nanoparticles in various fields may not support their use in medicine due to inconsistent data on toxicity as well as the lack of a centralized toxicity database. Inconsistent toxicological studies and lack of mechanistic understanding have been the reasons for limited understanding of their toxicological aspects. These nanoparticles, when underivatized or pristine, are considered as safe, however less reactive. The derivatized forms or functionalization changes their chemistry significantly to modify their biological effects including toxicity. They can cause acute and long term injuries in tissues by penetration through the the blood-air barrier, blood-alveolus barrier, blood-brain barrier, and blood-placenta barrier. and by accumulating in the lung, liver, and spleen . The toxicological effects are manifested through inflammatory response, DNA damage, apoptosis, autophagy and necrosis. Other factors that largely influence the toxicity of carbon nanotubes, graphenes and fullerenes are the concentration, functionalization, dimensional and surface topographical factors. Thus, a better understanding of the toxicity profile of CNTs, graphene-family nanomaterials and fullerenes in humans, animals and the environment is of significant importance, to improve their biological safety, to facilitate their wide biological application and for the successful commercial application. The exploration of appropriate cell lines to investigate specific receptors and intracellular targets as well as chronic toxicity beyond the proof-of-concept is required.
Keywords: Carbon nanotubes, graphenes, fullerenes, toxicity, centralized toxicity database, apoptosis, autophagy.
[http://dx.doi.org/10.2174/1381612821666150302153406] [PMID: 25732658]
[http://dx.doi.org/10.1007/s11010-011-0739-z] [PMID: 21298324]
[http://dx.doi.org/10.1016/j.jpha.2019.04.003] [PMID: 31929938]
[http://dx.doi.org/10.1289/ehp.10924] [PMID: 18795165]
[http://dx.doi.org/10.1016/j.pharmthera.2008.10.009] [PMID: 19103221]
[http://dx.doi.org/10.1021/nl2011214] [PMID: 21657258]
[http://dx.doi.org/10.1039/b211328g]
[http://dx.doi.org/10.1021/nl071303v] [PMID: 18044946]
[http://dx.doi.org/10.1021/nn900416z] [PMID: 19459622]
[http://dx.doi.org/10.3109/15376516.2012.754534] [PMID: 23193995]
[http://dx.doi.org/10.1021/ac801469b] [PMID: 18998708]
[http://dx.doi.org/10.1166/jnn.2011.3520] [PMID: 21449398]
[http://dx.doi.org/10.1166/jnn.2011.4976] [PMID: 22413351]
[http://dx.doi.org/10.2174/1573413715666181204113525]
[http://dx.doi.org/10.1166/jnn.2004.146] [PMID: 15656196]
[http://dx.doi.org/10.1016/j.carbon.2007.03.035]
[http://dx.doi.org/10.1186/1743-8977-6-16] [PMID: 19523217]
[http://dx.doi.org/10.1038/nnano.2008.111] [PMID: 18654567]
[http://dx.doi.org/10.1021/nn200595c] [PMID: 21800904]
[http://dx.doi.org/10.1039/b502429c] [PMID: 16880981]
[http://dx.doi.org/10.1007/s10753-010-9182-7] [PMID: 20174859]
[http://dx.doi.org/10.1016/j.toxlet.2006.08.019] [PMID: 17169512]
[http://dx.doi.org/10.1021/es048729l] [PMID: 15787380]
[http://dx.doi.org/10.1073/pnas.1110013108] [PMID: 22084097]
[http://dx.doi.org/10.1093/toxsci/kfg243] [PMID: 14514958]
[http://dx.doi.org/10.1152/ajplung.00084.2005] [PMID: 15951334]
[http://dx.doi.org/10.1093/toxsci/kfp247] [PMID: 19822600]
[http://dx.doi.org/10.1002/jat.3765] [PMID: 30605223]
[http://dx.doi.org/10.1021/nl0507966] [PMID: 16159204]
[http://dx.doi.org/10.1186/1465-9921-7-53] [PMID: 16571143]
[http://dx.doi.org/10.1002/jbt.20296] [PMID: 19827037]
[http://dx.doi.org/10.1016/j.addr.2013.05.011] [PMID: 23751780]
[http://dx.doi.org/10.1016/j.toxlet.2008.11.019] [PMID: 19114091]
[http://dx.doi.org/10.7150/thno.3618] [PMID: 22509195]
[http://dx.doi.org/10.2147/IJN.S109950] [PMID: 27621623]
[http://dx.doi.org/10.1016/j.micron.2012.08.008] [PMID: 23000350]
[http://dx.doi.org/10.1021/nn406484b] [PMID: 24871084]
[http://dx.doi.org/10.1371/journal.pone.0080964] [PMID: 24260521]
[http://dx.doi.org/10.1021/acsnano.5b02358] [PMID: 26043308]
[http://dx.doi.org/10.1016/j.biomaterials.2015.02.083] [PMID: 25890741]
[http://dx.doi.org/10.1007/s11356-020-09667-3] [PMID: 32548744]
[http://dx.doi.org/10.1093/ndt/gfs499] [PMID: 23136218]
[http://dx.doi.org/10.1016/j.toxlet.2004.08.015] [PMID: 15585362]
[http://dx.doi.org/10.1088/0957-4484/17/2/008]
[http://dx.doi.org/10.1590/1414-431X20143894] [PMID: 24863649]
[http://dx.doi.org/10.15171/bi.2016.11] [PMID: 27525224]
[http://dx.doi.org/10.1098/rsif.2009.0252.focus] [PMID: 19726441]
[http://dx.doi.org/10.1080/10641960500386817] [PMID: 16443565]
[http://dx.doi.org/10.1016/j.carbon.2008.12.032]
[http://dx.doi.org/10.3109/17435390.2016.1153165] [PMID: 27027670]
[http://dx.doi.org/10.1016/j.yrtph.2011.08.007] [PMID: 21893152]
[http://dx.doi.org/10.1016/j.carbon.2005.08.006]
[http://dx.doi.org/10.1016/j.tox.2008.12.023] [PMID: 19150385]
[http://dx.doi.org/10.1016/j.nano.2006.07.005] [PMID: 17292138]
[http://dx.doi.org/10.1080/10915810701225133] [PMID: 17454250]
[http://dx.doi.org/10.1007/s10439-010-0151-y] [PMID: 20824344]
[http://dx.doi.org/10.1002/smll.201201463] [PMID: 23097249]
[http://dx.doi.org/10.1021/nn200372g] [PMID: 21615177]
[http://dx.doi.org/10.2147/IJN.S123345] [PMID: 28280324]
[http://dx.doi.org/10.1186/1743-8977-11-3] [PMID: 24405760]
[http://dx.doi.org/10.1038/318162a0]
[http://dx.doi.org/10.1016/j.yrtph.2010.08.017] [PMID: 20800639]
[http://dx.doi.org/10.1093/toxsci/kfp265] [PMID: 19901017]
[http://dx.doi.org/10.1111/j.1742-7843.2008.00266.x] [PMID: 18684229]
[http://dx.doi.org/10.1007/s11224-017-0957-4]
[http://dx.doi.org/10.1080/1536383X.2019.1634055]
[http://dx.doi.org/10.1016/1074-5521(95)90219-8] [PMID: 9383440]
[http://dx.doi.org/10.1093/toxsci/kfm243] [PMID: 17878152]
[http://dx.doi.org/10.1155/2020/8061246] [PMID: 32148657]
[http://dx.doi.org/10.1021/nl051866b] [PMID: 16351219]
[http://dx.doi.org/10.1177/019262339802600117] [PMID: 9502397]
[http://dx.doi.org/10.1021/ja00089a067]
[http://dx.doi.org/10.1021/nl0489586]
[http://dx.doi.org/10.1021/es0609708] [PMID: 17180994]
[http://dx.doi.org/10.1093/carcin/17.10.2163] [PMID: 8895484]
[http://dx.doi.org/10.1021/tx200339h] [PMID: 21954945]
[http://dx.doi.org/10.1002/adma.201203700] [PMID: 23494834]
[http://dx.doi.org/10.1007/s00204-020-02717-2] [PMID: 32240330]
[http://dx.doi.org/10.1016/j.addr.2016.04.028]
[http://dx.doi.org/10.1186/s12989-016-0168-y] [PMID: 27799056]
[http://dx.doi.org/10.1021/tx400385x] [PMID: 24422439]
[http://dx.doi.org/10.1039/C7TX00278E] [PMID: 30090566]
[http://dx.doi.org/10.1186/s12989-016-0120-1] [PMID: 26864058]
[http://dx.doi.org/10.1016/j.biomaterials.2013.01.001] [PMID: 23340196]
[PMID: 25152621]
[http://dx.doi.org/10.1021/acsnano.8b04758] [PMID: 30387986]
[http://dx.doi.org/10.2174/0929867324666170413124915] [PMID: 28412902]