Tumor-microenvironment-activated In Situ Self-assembly Of Sequentially-responsive Biopolymer For Targeted Photodynamic Therapy

The cancer is one of the diseases of serious threat to mankind’s health and life nowadays,Among cancers,breast cancer accounts for the vast majority of women,Despite the long-term efforts of scientists,surgical incision methods have made some progress in early stage breast cancer patients,but for the vast majority of advanced patients,the prognosis is worse.The risk of recurrence after surgery is high,leading to increased morbidity and mortality of breast cancer patients each year.Therefore,how to attack breast cancer seems imminent.Traditional methods include surgical resection,chemotherapy and radiotherapy.With the development of high-tech technology,photodynamic therapy has attracted great attention in the conquest of tumors,Photodynamic therapy involves injecting a photosensitizer into the body and then irradiating it with a specific laser to trigger a photochemical reaction that produces singlet oxygen,selectively destroying cancer cells.However,due to the strong hydrophobicity of the photosensitizer,the circulation time in the blood is shorter,it is easy to be removed.Based on this,A sequentially-responsive photosensitizer-integrated biopolymer is developed for the tumor-specific photodynamic therapy,which is capable of forming long-retained aggregates in situ inside tumor tissues.Specifically,the photosensitizer zinc phthalocyanine(Zn Pc)is conjugated with polyethylene glycol(PEG)via p H-liable maleic acid amide linker and then immobilized unto the hyaluronic acid(HA)chain using redox-cleavable disulfide linker.The PEG segment could enhance blood circulation of the molecular carrier after intravenous administration and be shed after reaching the acidic tumor microenvironment,allowing the remaining fragment to self-assemble into large clusters in situ to avoid backward diffusion and improve tumor retention.This process is driven by hydrophobic interaction and does not require additional external actuation.The aggregates are then internalized by the tumor cells via HA-facilitated endocytosis,and the high glutathione level in tumor cells would eventually lead to the release of monomolecular Zn Pc molecule for unabated photodynamic efficacy.This tumor-triggered morphology-based delivery platform is constructed with clinically tested components and could potentially be applied to other hydrophobic therapeutics.