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. 2015 Mar 5;6:6456. doi: 10.1038/ncomms7456

Figure 1. A highly pH-sensitive carrier.

Figure 1

(a) A schematic representation of the gene loaded carrier. Its biocompatible, contracted, negatively charged form circulates freely in a passive form until extravasation into tumour tissue characterized by lowered pH. Tumour acidosis switches the carriers charge to enhance cellular interaction and uptake. Protonation of the carriers’ amino groups leads to distention of the polymer chains, dilation and expulsion of payloads. Here p53 and KillerRed genes transfect tumour cells. p53 triggers apoptosis while illumination of KillerRed protein generates ROS and subsequent intracellular damage, further promoting cell apoptosis. (b,c) ζ-Potential (b) and hydrodynamic diameter (c) of the DNA-complex and bPEI25K/DNA-complex as a function of pH for varying bPEI25K/DNA/copolymer weight ratios. Data show the mean of the measurements conducted in triplicate±s.d. (d) Fluorescence intensity after cellular uptake of the bPEI25K/DNA-complex (bPEI25K/DNA weight ratio: 2/1) or DNA-complex (bPEI25K/DNA/copolymer weight ratio: 0.5/1/1) monitored using Alexa Fluor 488 labelling of plasmid DNAs over the period of several cycles of pH between 7.4 and 6.8 or incubated at only pH 7.4 or 6.8. Results show mean of measurements conducted in triplicate±s.d. Oscillating charge of the carrier results in a step-like response in cellular uptake of the DNA-complex with fluctuating pH.