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.
Highlights
The tumor microenvironment does not refer to cancer cell clusters and to the cancer-associated fibroblasts, myoblasts, epithelial cells, and immune cells along with the extracellular matrix (ECM), oxygen level, pH, and so on [1,2,3,4]
Maleic acid amide derivatives conjugated to amine groups which have pH-responsive charge-conversion ability [10,11,12,13,14,15,16,17], acid-labile linkages such as a hydrazone bond [18,19,20,21], and polypeptides which are composed of both cationic amino acids and anionic amino acids [22,23,24,25,26,27] have been utilized for gene or drug delivery systems
The sharp-edged sheet structure of PEI-rGO was transformed to spherical nanostructures with vague edges by PK5E7 coating
Summary
The tumor microenvironment does not refer to cancer cell clusters and to the cancer-associated fibroblasts, myoblasts, epithelial cells, and immune cells along with the extracellular matrix (ECM), oxygen level, pH, and so on [1,2,3,4]. Conventional cationic gene or drug delivery systems are prone to aggregate with negatively-charged serum protein due to the electrostatic interaction and to be eliminated via renal clearance or reticuloendothelial system [9]. In order to overcome this problem and utilize the acidic condition of the tumor microenvironment, the various strategies about gene or drug delivery systems using pH-responsive polymers have been pursued. It is expected that these polymeric gene or drug delivery systems can enhance the delivery efficiency, shielding the interaction with negatively-charged serum proteins under normal physiological pH conditions and improving the cellular uptake by conversion to positively-charged systems through the specific pH-responsive charge-conversion behaviors in the acidic tumor environment (hydrolysis, protonation/deprotonation, etc.)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
