Nanoparticles: A promising strategy to overcome microbial drug resistance

Hey Steemians,

Today I will be talking about one of the applications of nanotechnology against bacterial infections. For about 2000 years ago, several infections were treated by mixtures with antimicrobial properties, ancient Egyptians and Greek cultures are known to use plant extract and other materials to treat infection.  

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Paul Ehrlich in late 1880s has started working on antimicrobial and in 1907 he discovered as a medicinally useful drug now its called arshenamine. After that several other drug also released with antimicrobial property, later on Ehrlich received Nobel Prize in Physiology or Medicine. With all these there are several natural antibiotics are also available, you may remember Penicillin given by Louis Paster having the same antimicrobial activity.  

Most commonly used antibacterial agents are chemically modified products of penicillins, cephalosporins or carbapenems. Antibacterial agents are of two types bactericidal (kills bacteria) and bacteriostatic (slows down bacterial growth). But one of the major problem which world facing is antibacterial resistant due to misuse of the drugs. So scientists are constantly looking for developing new methods to tackle this situation and on the same time stop bacterial infection. 

The various mechanism by which nanoparticles act on bacterial is by creating oxidative stress, metal ion release and non-oxidative mechanism. These multiple simultaneous actions taking place in the bacterial cell require multiple gene mutations to acquire resistance to nanoparticles, thus it is difficult for bacteria to develop resistant against them (1).

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Now we will talk about what make these nanoparticles efficient candidate for antibacterial and how they act on the cells (mechanism). 

Nanoparticles have small size and large surface area to volume ratio which results in complete change of many properties like mechanical, electrical, chemical, electro-optical compared to their bulk counterpart (2). There one dimension ranges from 1-100 nm (3).

Although the action mechanism of nanoparticles is not completely understood, it has been shown that they destroy the cell by binding to cell membrane by electrostatic interaction and by generation of reactive oxygen species (ROS) which creates oxidative stress inside the cell. When bacterial cell encounters stress conditions like heat or chemical treatment or invasion by foreign body they produce reactive oxygen species to overcome the situation. Every bacterial cell have pathway to resist small amount of reactive oxygen species like glutathione redox system, but when higher amount of ROS are present for long time it results in cell damage. The large surface area of nanoparticles results in production of large amount of reactive oxygen species (4). It has been also shown by some scientists that NP inhibits the stem cell differentiation and reduction in protein synthesis (5). Nanoparticles also lead to cytoskeletal deformations (concentration dependent effect). Ions such as ferric ions released from the lysosome in presence of nanoparticles enter cytoplasmic iron pool and affect cyclin-dependent kinases (6).IImage Source

Biofilm forming bacteria gives tough fight to many antibacterial drugs and nanoparticles. The electrostatic interaction between nanoparticle and cell membrane charge influence the activity of nanoparticles. Scientist has shown that marine biofilms can uptake silver nanoparticle (AgNP) and these nanoparticles inhibit the growth of biofilm (7). Ehud Banin group from Bar-Ilan University in 2012 has developed magnesium fluoride nanoparticles coated catheters to inhibit growth of biofilm formation and spread of infection in hospital environment (8).

A recent work from University of Manchester has created washable and durable polymeric material coated with copper nanoparticles, which can be used in hospital environment to inhibit spread of infections. Cu2+ release inhibit the growth of bacteria. For the preparation of this polymer the copper nanoparticles are cross-linked in polymeric matrix which reduces the chances of its release in solution. In experiments this material showed good results against Staphylococcus aureus and E.coli (9).

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Last but very important point is systematic use of nanoparticles and reduces the risk of its leakage in the environment. There are many microbes with are beneficial to us and play many important role in nutrient cycling and nitrogen fixation. Leakage of nanoparticles in soil and water may lead to damage of useful microbes. Silver nanoparticles have shown toxicity against nitrifying bacteria and loss of these bacteria from environment will result in decreased nitrogen removal and interfere in plant growth (10). So researchers and industries should use nanoparticles against harmful bacteria and take proper measures to prevent there leakage.

Reference

Wang et. al., 2017 The antimicrobial activity of nanoparticle: present situation and prospects for the future. 12(1); 1227-1249

Hajipour et. al., 2012 Antibacterial property of nanoparticles. 30(10); 499-511

Soenen et. al., 2011 Cellular toxicity of inorganic nanoparticles: common aspects and guidelines for improved nanotoxicity evaluation. 6(5);446-465  

Chen et al., 2010 The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cell. 245;272 

Huang et al., 2009 The promotion of human mesenchymal stem cell proliferation by superparamagnetic iron oxide nanoparticle. 30;3645

Lelouche et. al., 2012 Antibiofilm surface funtionlization of cathters by magnesium fluoride nanoparticles. 7; 1175-1188

Sun et. al., 2018 Durable and Washable Antibacterial Copper Nanoparticles Bridged by Surface Grafting Polymer Brushes on Cotton and Polymeric Materials. 2018;1-7

Choi et. al., 2008 Size Dependent and Reactive Oxygen Species Related Nanosilver Toxicity to Nitrifying Bacteria 42(12); 4583-4588 

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Vinamra