Intracellular transport of biomacromolecular drugs by a designed microgel capsule with pH/redox stimulus-responsiveness

Abstract

Biological macromolecular drugs usually have good efficacy and recognition performance. However, due to their large molecular weight and easy degradation/inactivation, general carriers are difficult to transport them into cell stably and safely. Here, a pH/redox dual-responsive microgel capsule was prepared for constructing a double-locked drug delivery system. Firstly, the pH-sensitive poly(ethyleneimine)-block-poly(2-(diisopropylamino ethylmethacry-late)-block-poly(ethyleneimine) triblock copolymers (PEI-PDPA-PEI) were synthesized for preparing polymer vesicles. The PEI layer was crosslinked by disulfide groups to finally obtain pH/redox dual-responsive microgel capsule, marked as P-VesicleGEL. Then, the P-VesicleGEL was used to encapsulate different types of drugs (doxorubicin hydrochloride, rhodamine, proteins, aptamer), and had a higher loading capacity than the corresponding polymer micelles for macromolecules. Compared with small molecules, P-VesicleGEL had much better "double-locked" function for macromolecules. I.e., only when the two “locks” were opened simultaneously the release could be triggered. Furtherly, cell experiments had proved that the P-VesicleGEL had excellent biocompatibility and cell transfection ability. It could not only effectively identify normal and cancer cells, but also transport biological drugs that were difficult to enter into cells by themselves. The microgel capsule designed here is expected to be applied for the intracellular delivery/release of biological macromolecular drugs.