Effect of pH-Responsive Charge-Conversional Polymer Coating to Cationic Reduced Graphene Oxide Nanostructures for Tumor Microenvironment-Targeted Drug Delivery Systems

Abstract

Tumor tissue represents a slightly acidic pH condition compared to normal tissue due to the accumulation of lactic acids via anaerobic metabolism. In this work, pH-responsive charge-conversional polymer (poly(ethylene imine)-poly(l-lysine)-poly(l-glutamic acid), PKE polymer) was employed for endowing charge-conversional property and serum stability to poly(ethylene imine) conjugated reduced graphene oxide-based drug delivery system (PEI-rGO). Zeta-potential value of PEI-rGO coated with PK5E7 polymer (PK5E7(PEI-rGO)) was −10.9 mV at pH 7.4 and converted to 29.2 mV at pH 6.0, showing pH-responsive charge-conversional property. Sharp-edged plate morphology of PEI-rGO was transformed to spherical nanostructures with vague edges by PK5E7 coating. Size of PK5E7(PEI-rGO) was found to be smaller than that of PEI-rGO in the serum condition, showing its increased serum stability. Loaded doxorubicin (DOX) in PK5E7(PEI-rGO) could be released rapidly in lysosomal condition (pH 5.0, 5 mM glutathione). Furthermore, DOX-loaded PK5E7(PEI-rGO) showed enhanced anticancer activity in HeLa and A549 cells in the tumor microenvironment-mimicking condition (pH 6.0, serum), which would be mediated by non-specific cellular interaction with decorated serum proteins. These results indicate that the pH-responsive charge-conversional PKE polymer coating strategy of cationic rGO nanostructures possesses a potential for acidic tumor microenvironment-targeted drug delivery systems.

Cytotoxicity of Carbon Nanotubes, Graphene, Fullerenes, and Dots

“…The optical absorption spectroscopy of carbon nanomaterials for cytotoxic investigations was performed in Refs. [50,67]. In this section, we review the most interesting investigations.…”

“…The toxicology issues are connected with drug delivery and bioimaging. The drug delivery is controlled by water solubility, biocompatibility, blood circulation time, targeting, and accumulation of therapeutics in diseased cells and tissues for carbon nanotubes [39][40][41][42][43][44][45][46][47][48][49], graphene [50][51][52][53][54][55][56][57][58][59][60][61][62], fullerenes [63], dots [64][65][66][67]. The diagnostic method, bioimaging, is connected with the penetration of drugs and diagnostic agents into tissues and cells and the sensitivity of detection.…”

Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy

“…In a similar study, Jafarizad et al prepared Au nanoparticle-loaded rGO as a covalent drug delivery system for pH-dependent release of mitoxantrone (MTX) [ 74 ]. For polymer coating, Ryu and co-workers prepared PEI-rGO nanocarrier for pH-responsive delivery of DOX to Hela and A549 cancer cell lines [ 75 ]. The drug-loaded nanocomposite was further coated with pH-responsive charge-conversional polymer polyethyleneimine-poly- L -lysine-poly- L -glutamic acid (PKE) to endow charge-conversional property and serum stability to PEI-rGO-based drug delivery system.…”

Cavitation-Enhanced Delivery of the Nanomaterial Graphene Oxide-Doxorubicin to Hepatic Tumors in Nude Mice Using 20 kHz Low-Frequency Ultrasound and Microbubbles

“…The resulting product was purified by dialyzing (MWCO 8000-10,000 Daltons) against deionized water. The DOX loading in GO was confirmed by measuring the absorbance (300-700 nm) of GO and GO-DOX, respectively, using a microplate reader (Synergy H1; BioTek, Winooski, VT, USA) [47].…”