Bacteriomimetic poly-γ-glutamic acid surface coating for hemocompatibility and safety of nanomaterials

Abstract

Poly-γ-glutamic acid (PGA), a major component of the bacterial capsule, is known to confer hydrophilicity to bacterial surfaces and protect bacteria from interactions with blood cells. We tested whether applying a bacteriomimetic surface coating of PGA modulates interactions of nanomaterials with blood cells or affects their safety and photothermal antitumor efficacy. Amphiphilic PGA (APGA), prepared by grafting phenylalanine residues to PGA, was used to anchor PGA to reduced graphene oxide (rGO) nanosheets, a model of hydrophobic nanomaterials. Surface coating of rGO with bacterial capsule-like APGA yielded APGA-tethered rGO nanosheets (ArGO). ArGO nanosheets remained stable in serum over 4 weeks, whereas rGO in plain form precipitated in serum within 5 minutes. Moreover, ArGO did not interact with blood cells, whereas rGO in plain form or as a physical mixture with PGA formed aggregates with blood cells. Mice administered ArGO at a dose of 50 mg/kg showed 100% survival and no hepatic or renal toxicity. No mice survived exposure at the same dose of rGO or a PGA/rGO mixture. Following intravenous administration, ArGO showed a greater distribution to tumors and prolonged tumor retention compared with other nanosheet formulations. Irradiation with near-infrared light completely ablated tumors in mice treated with ArGO. Our results indicate that a bacteriomimetic surface modification of nanomaterials with bacterial capsule-like APGA improves the stability in blood, biocompatibility, tumor distribution, and photothermal antitumor efficacy of rGO. Although APGA was used here to coat the surfaces of rGO, it could be applicable to coat surfaces of other hydrophobic nanomaterials.

A Systematic Review and Critical Analysis of the Role of Graphene-Based Nanomaterials in Cancer Theranostics

“…Besides chemotherapy, and contrastingly to a previous review that covered studies reported from 2012–2014 [97], we found that the most explored therapeutic strategy of GBNs is PTT [5,6,46,50,51,58,59,60,61,62,64,66,69,70,72,73,74,75,76,77,79,86,90,92,93]. In the time frame of that review, chemotherapy was the focus of using GBNs, while in the last 6 years, covered by this systematic review, researchers have shown the appealing role of GBNs in PTT.…”

“…All 55 studies report the development of GBNs alone [44,45] or often functionalized with different additives [5,6,7,8,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94] for cancer theranostic applications. Each of these studies presented the assessment of the individual role of GBNs either in therapeutic or diagnostic applications.…”

“…Each of these studies presented the assessment of the individual role of GBNs either in therapeutic or diagnostic applications. Within the complete set of studies, the therapeutic performance was evaluated in cellular [6,49,50,52,53,55,63,68,70,80,81,82,83,84,85,86,89,94], or animal models [46,71,77], or both [5,7,46,47,48,51,56,57,58,59,60,61,62,64,66,69,72,73,74,75,76,78,79,81,87,88,90,91,92,93]. In the case of cellular studies, GBNs were incubated at a defined concentration or in a range of concentrations and some studies involved the application of GBNs solely [46,53,54,55,63,68,71,…”

“…In the case of cellular studies, GBNs were incubated at a defined concentration or in a range of concentrations and some studies involved the application of GBNs solely [46,53,54,55,63,68,71,78,82,91] or conjugated with the exposure to a laser source of a defined potency, wavelength, and time [5,6,7,8,44,45,47,48,49,50,51,52,56,57,58,59,60,61,62,64,65,66,67,69,70,72,73,74,75,76,77,79,80,81,83,84,85,86,87,88,89,90,92,93,94]. With the exception of few studies [45,47,87,94], the laser used is a near infrared light source (NIR) that has a trigger effect ...…”

Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle

“…PPGA was synthesized through amide coupling between γ -PGA (50 kDa; BioLeaders, Daejeon, Republic of Korea) and phenylalanine ethylester (Sigma, St. Louis, MO, USA) as described previously 21 . In brief, 10 g of γ -PGA was dissolved in 1 L of 0.3 mol/L NaHCO 3 solution, to which was added 15 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC; Tokyo Chemical Industry Co., Ltd., Tokyo, Japan), followed by stirring for 30 min on ice.…”