Nanopar­ti­cles coated with an­tibi­otic elim­i­nate drug-re­sis­tant bac­te­ria

The Star Malaysia - Star2 - - Science - By KA­RINA TOLEDO

A NEW strat­egy to com­bat an­tibi­otic-re­sis­tant bac­te­ria has been de­scribed by Brazil­ian re­searchers in Sci­en­tific Re­ports, an on­line jour­nal owned by Springer Na­ture.

The method con­sists of coat­ing nanopar­ti­cles that are made of sil­ver and sil­ica – po­ten­tially toxic to both micro­organ­isms and hu­man cells – with a layer of an­tibi­otic. Ow­ing to chem­i­cal affin­ity, the re­sult­ing na no phar­ma­ceu­ti­cal acts only on the pathogens and is in­ert to the or­gan­ism.

“We used the an­tibi­otic as a sort of bait to have the nanopar­ti­cles tar­get the bac­te­ria with a large amount of the drug. The com­bined ac­tion of the drug with the sil­ver ions proved ca­pa­ble of killing even re­sis­tant micro­organ­isms,” said Ma­teus Borba Car­doso, a re­searcher at the Na­tional En­ergy & Ma­te­ri­als Re­search Cen­ter (CNPEM).

In pre­vi­ous ar­ti­cles, the group showed that nanopar­ti­cles can also be used to make anti-can­cer chemo­ther­apy more ef­fec­tive by de­liv­er­ing the drug di­rectly to tu­mour cells and leav­ing healthy cells in­tact. The nanopar­ti­cles could also be ap­plied to po­ten­tially in­ac­ti­vate HIV in trans­fu­sion blood bags, for ex­am­ple.

“There are com­mer­cial drugs that con­tain nanopar­ti­cles, which typ­i­cally serve to coat the ac­tive in­gre­di­ent and ex­tend its life­time in­side the or­gan­ism. Our strat­egy is dif­fer­ent. We dec­o­rate the sur­face of the nanopar­ti­cles with cer­tain chem­i­cal groups that di­rect them to the site where they’re de­signed to act, so they’re highly se­lec­tive,” Car­doso said.

In the most re­cent ar­ti­cle, the group de­scribed a scheme to syn­the­sise nanopar­ti­cles con­sist­ing of a sil­ver core over­laid with por­ous sil­ica to al­low the pas­sage of ions.

Sev­eral mol­e­cules of the an­tibi­otic ampi­cillin were ap­plied to the sur­face in an ar­range­ment that, ac­cord­ing to Car­doso, was far from ran­dom.

“We used molec­u­lar mod­el­ling to find out which part of the ampi­cillin mol­e­cule in­ter­acted most with the bac­te­rial mem­brane,” he said. “We then ar­ranged all the mol­e­cules of the drug so that this key part was fac­ing out­ward from the nanopar­ti­cle, in­creas­ing the like­li­hood of in­ter­ac­tion with the pathogen.”

Hu­bert Karl Stassen, of the Chem­istry In­sti­tute at the Fed­eral Uni­ver­sity of Rio Grande do Sul (UFRGS), col­lab­o­rated on the molec­u­lar model­ing stage.

The ef­fec­tive­ness of the nanoan­tibi­otic com­pared with that of con­ven­tional ampi­cillin was as­sessed us­ing two dif­fer­ent strains of Escherichia coli, a bac­terium that nor­mally in­hab­its the gut flora of mam­mals and that can cause food poi­son­ing in cer­tain sit­u­a­tions.

In the non-re­sis­tant strain, nearly 100% of the micro­organ­isms died when at­tacked both by ampi­cillin in its con­ven­tional form and by the drug com­bined with sil­ver.

In the re­sis­tant strain, how­ever, only the nanoan­tibi­otic was ef­fec­tive.

The next step was to test the ef­fect on hu­man kid­ney cells. The sil­ver and sil­ica nanopar­ti­cles with­out ampi­cillin proved highly toxic, while con­ven­tional ampi­cillin and ampi­cillin com­bined with sil­ver were found to be equally safe.

“Con­fo­cal mi­croscopy im­ages show that be­sides be­ing non-toxic, the nanopar­ti­cle coated with ampi­cillin doesn’t in­ter­fere with the cell cy­cle. The phases of mi­to­sis take their course with­out any al­ter­ations,”

Car­doso said.

In his view, the same strat­egy could be used to com­bat other bac­te­rial species that have de­vel­oped re­sis­tance to an­tibi­otics.

In ad­di­tion, the drug ap­plied to the sur­face of the nanopar­ti­cle can be var­ied in or­der to treat dif­fer­ent types of in­fec­tion.

How­ever, the sys­tem has one draw­back: be­cause sil­ver and sil­ica are in­or­ganic, the nanopar­ti­cles are not metabolised and thus tend to build up in the or­gan­ism.

“We don’t yet know where the build-up oc­curs or what ef­fect it has,” Car­doso said. “To find out, we’ll need to do tests in an­i­mals. In any event, we’re con­tin­u­ing to

im­prove the sys­tem in or­der to make it safer.”

One pos­si­bil­ity would be to use a sec­ond an­tibi­otic with a dif­fer­ent com­po­nent than sil­ver in the core. An­other would be to de­velop a nanopar­ti­cle small enough to be ex­creted in urine.

Mean­while, Car­doso added, in its cur­rent form, the nanoan­tibi­otic could be used to treat ex­treme cases, such as hospi­tal in­fec­tions that do not re­spond to con­ven­tional an­tibi­otics.

“If nanopar­ti­cles do build up in the or­gan­ism in these cases, it would be an ac­cept­able price to pay to avoid death,” he said. – Agên­cia FAPESP

The ef­fec­tive­ness of the nanoan­tibi­otic was as­sessed us­ing two dif­fer­ent strains of Escherichia coli, a bac­terium that nor­mally in­hab­its the gut flora of mam­mals and that can cause food poi­son­ing in cer­tain sit­u­a­tions. — AFP

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