PH And MMP-2 Dual-Sensitive Nanosystem For Combined Chemotherapy And Antiangiogenic Therapy

Malignancy is a kind of chronic and frequently-occurring disease that is nowadays seriously threatening human health and survival.In order to combat tumors in a more aggressive method,compared with monotherapy,combination therapy has shown a synergistic effect of high antitumor activity in preclinical and clinical cancer treatment.In order to solve the problem of inconsistent pharmacokinetics of various drugs during combination therapy,the nano-delivery system has been widely developed and applied.However,to get better outcomes after treatment,according to the further and solid researches,anti-tumor combination therapy is no longer a simple group of the same kind of drugs,but a combination of chemotherapy with immunotherapy,radiotherapy or anti-angiogenic therapy.In this situation,the new therapeutic model raises higher standards and challenges for existing nano-delivery systems.Nano-delivery systemsare no longer required to simply carry multiple drugs,but to ensure that different drugs could target different cells within the tumor micro-environment.Thereby different therapies can reach their target cells and achieve a prospective anti-tumor result.This mode of treatment poses new requirements for nano-delivery systems.Therefore,in accordance with the above background,we have designed a pH and MMP-2 dual-sensitive nano-system.This system can copackage a variety of drugs,and can achieve accurate multi-drug co-delivery within the tumor site.As the combination of chemotherapy and antiangiogenesis is common to use at the clinical stage,we choose the classic anti-angiogenic drugs Sorafenib and common chemotherapy drug doxorubicin(DOX)to be both encapsulated in the nano-system.Through in vitro cell experiments and in vivo animal experiments,the effect of the drugloaded nano-system on the treatment of malignant breast cancer was studied and evaluated.In this study,the pH and MMP-2 dual-sensitive nanosystem was constructed for the first time.The structure and drug release behaviors of the dual-sensitive and drug-loaded nanoparticles were systematically evaluated.The anti-angiogenesis and anti-tumor activity were evaluated,which shows the significant anti-tumor effect after combined anti-angiogenic therapy and chemotherapy.