Redox-Responsive Aie Nanogel For The Targeted Delivery Of Anti-Cancer Drug And Real-Time Intracellular Imaging

The threat of cancer to human life and health has become increasingly acute,and nanomaterials provide new opportunities for the efficient treatment of cancer.In addition,the use of“green”synthetic ideas and strategies to build a drug delivery system with low material toxicity and high biocompatibility has received increasing attention.Because nanogels（HNPs）can be prepared in aqueous solutions and have good biocompatibility in themselves,they have shown increasing value in the study of drug delivery systems.On the basis of traditional HNPs,further targeted drug delivery,controlled release,and real-time intracellular imaging are of great significance for efficient treatment of contemporary cancers.Based on this,we design and synthesize novel HNPs with targeted,redox-responsive and real-time intracellular imaging functions for improving the anti-cancer efficiency of doxorubicin hydrochloride（DOX）.We synthesized a HA-ss-ATRA amphiphilic polymer by linking a hydrophilic hyaluronic acid（HA）and a hydrophobic all-trans-retinoic acid（ATRA）via a disulfide-containing cystamine as a linker.Further,the HA-ss-ATRA/TPENH₂ target product was obtained by chemically modifying an aggregation-induced emission（AIE）fluorophore（TPENH₂）.Moreover,we also synthesized a HA-ATRA/TPENH₂ complex without a disulfide bond as a control group.The target product complex self-assembles into HNPs through hydrophilic-hydrophobic interaction in the whole aqueous solution.In vitro release study showed that HA-ss-ATRA/TPENH₂ HNPs can rapidly lyse and release drugs in the presence of high concentrations of glutathione,demonstrating their good redox responsiveness.Moreover,after preparation of HNPs in the whole aqueous solution,the MTT cytotoxicity studies showed that the unloaded HNPs did not produce significant cytotoxicity to cancer cells Hep G-2 and normal cell 293T cells,demonstrating its good biocompatibility and low material toxicity.Importantly,DOX-loaded HNPs produced higher cancer-fighting efficiency than the same concentration of pure DOX.Finally,The observations of HNPs by fluorescence microscopy showed that HNPs have strong AIE fluorescence themselves and realize the real-time intracellular imaging while overcoming aggregation-caused quenching effect.We hope that HA-ss-ATRA/TPENH₂ HNPs can provide a new idea for the construction of a new type of“green”multifunctional drug delivery system.