An Mitochondrial-targeting And Dual-responsive Polymeric Nanoparticle For Effective Cancer Treatment

To achieve optimal delivery efficiency,most drugs need to play a role in specific organelles,the targeted delivery of therapeutic agent to cancer tissues and cells with nanoparticles has been widely investigated.Among a variety of cell organelles,mitochondria not only can maintain pivotal physiological functions but also are closely related to cell apoptosis.In,mitochondria function as place cells can not only regulate the physiological function of normal cells,and apoptosis is closely related with mitochondrial targeting can provide new ideas for the treatment of cancer.,As a concept of improving chemotherapy through mitochondrial targeting,so we design a stimuli-responsive mitochondria-targeting nanoparticle for cancer treatment.Here we described a rational mitochondria-targeted nanoparticle by conjunct targeted polymer TPP-PEG-ss-PLA.Doxorubicin(DOX)loaded micelles were firstly fabricated by the solvent evaporation method.Designed to neutralize the positive charge,chondroitin sulfate(CS)was then added.To evaluate the antitumor effect,both in vivo and in vitro experiments were investigated.JC-1 staining result confirm the permeability of the mitochondrial membrane with concomitant loss of mitochondrial membrane potential.The result of Confocal Laser Scanning Microscope(CLSM)confirmed that DOX enriched in both mitochondria and nucleus,this durg could damage the two organelles simultaneously.By investigating the mitochondrial membrane potential of tumor cells,it was found that CS/TPP-PEG-ss-PLA nanoparticles could significantly reduce the membrane potential of living tumor cells the in vivo antitumor effect on H22 bearing Babl/c mice displayed that the CS/TPP-PEG-ss-PLA@DOX possessed the best therapeutic efficacy.After 21 days treatment,the highest inhibitions of tumor growth are observed in CS/TPP-PEG-ss-PLA@DOX treatment groups.Therefore,the combination of mitochondria-targeting and reduction-sensitive DOX release could prove to be an effectual therapy for cancer treatment.