Construction of photosensitizer-hypoxia activated prodrug integrated prodrug self-assembled nanoparticles

Abstract

The invention belongs to the technical field of medicines and relates to a photosensitizer-hypoxia activated prodrug integrated prodrug. According to the invention, a photosensitizer and a hypoxia activated prodrug are connected through a bond which breaks under triggering by photo-induced electron transfer, a bond sensitive to active oxygen, or a bond which breaks under the triggering by photo-induced electron transfer and is sensitive or non-sensitive to active oxygen, so the photosensitizer and the hypoxia activated prodrug can be efficiently co-loaded and synchronously delivered. Pyropheophorbide a is used as a photosensitizer, PR104A is used as a hypoxia activated prodrug, a thioketal bond or monothioether bond or non-sensitive carbonate bond is employed for connecting pyropheophorbide with PR104A to synthesize an integrated prodrug, and then a self-assembled nanometer drug delivery system is prepared. According to the invention, a preparation process is simple; the drug loading capacity of the nanoparticles is high; the particle size of the nanoparticles is small and uniform, so the nanoparticles can be enriched at a tumor part through an EPR effect; while photodynamic therapy is conducted, the selective release of the hypoxia activated prodrug in the tumor is triggered through dual modes of PET and ROS; and the photodynamic therapy promotes the activation of the hypoxiaactivated prodrug, and significantly improves the synergistic anti-tumor effect of the photosensitizer and the hypoxia activated prodrug.

Description

technical field [0001] The invention belongs to the field of new excipients and new dosage forms of pharmaceutical preparations, relates to a photosensitizer-hypoxia-activated prodrug integrated prodrug and a synthesis method thereof, and also relates to the photosensitizer-hypoxia-activated prodrug integrated prodrug self-assembled nanometer Construction of particles and their use in drug delivery systems. Background technique [0002] Cancer is still a major disease that threatens human health. At present, chemotherapy is still the main treatment for cancer, but most chemotherapy drugs are cytotoxic drugs with narrow therapeutic window and poor tumor targeting, resulting in poor efficacy and toxic side effects. serious. Hypoxia-activated prodrugs are a class of prodrugs that are non-toxic or less toxic. They can be selectively activated in the hypoxic region of tumors to become anti-tumor drugs with cytotoxic activity. Compared with traditional chemotherapy drugs, they ha...

AI Technical Summary

Problems solved by technology

[0003] However, due to the differences in physicochemical and pharmacokinetic properties between hypoxia-activated prodrugs and photosensitizers, how to achieve efficient simultaneous drug delivery of the two is still an urgent problem to be solved.

Traditional nanocarriers can co-load hypoxia-activated prodrugs and photosensitizers by physical embedding, but this non-covalent co-loading strategy suffers from low drug loading, poor stability, and easy crystallization of drugs in the carrier. Issues such as early leakage and aggregation quenching effect of photosensitizer

Images