Fabrication of programmed photosensitizer-conjugated nanoassemblies by dual supramolecular self-assembly for photodynamic therapy of orthotopic hepatoma

Abstract

Supramolecular self-assembly has been extensively adopted as a promising strategy to fabricate nanoassemblies as drug carriers for cancer treatment. In this research, glutathione (GSH) activatable photosensitizer (PS)-conjugated nanoassemblies are fabricated by dual supramolecular self-assembly. Poly(ethylene glycol)-block-polylysine with pendant benzimidazole (PEG-b-PLys(BM)) is synthesized as the guest molecule of α-CD and β-CD. Chlorin e6 (Ce6) is loaded to the nanocarriers by the formation of polyrotaxanes between Ce6 conjugated α-CD (α-CD-SS-Ce6) and PEG block of PEG-b-PLys(BM). The Ce6 conjugated nanocarriers are then capped by (2-hydroxypropyl)-β-cyclodextrin (β-CD-HP) due to the host–guest interaction between β-CD-HP and benzimidazole (BM) to form supramolecular nanocarriers (BM-Ce6 NPs). BM-Ce6 NPs are negatively charged in physiological environment. However, because of the removal of β-CD-HP upon the protonation of BM, the surface charge of BM-Ce6 NPs can be converted to positive in acidic tumour microenvironment, which could lead to enhanced cellular internalization. Furthermore, Ce6 can be effectively released and activated in intracellular reductive environment, resulting in stronger reactive oxygen species (ROS) generation capability. The photodynamic therapeutic efficacy of BM-Ce6 NPs is evaluated on subcutaneous and orthotopic hepatoma model on nude mice. This research provides an innovative approach to fabricate drug nanocarriers by dual supramolecular self-assembly.