Biodegradable Sulfobetaines Zwitterionic Nanogels Drug Delivery System for Anticancer Therapy

Author:Men Yong Zhi

Supervisor:dong pin


Degree Year:2018





Cancer is one of the major threats to human health,the morbidity of cancer is increasing year by year,the head and neck cancer accouted for 5.6% of the incidence.Chemotherapy is one of the main treatments of cancer,especially to the patients with advanced cancer and systemic metastasis.However,the traditional chemotherapy drugs are often show low bioavailability and lethal side effects.To fabricate a favorable platform as drug-delivery which performed hydrophilic character,high drug loading content and superior stability in blood for cancer therapy was of great importance.In this work,novel reduction-responsive zwitterionic nanogels as a platform for tumor drug delivery was facilely fabricated through by one-step reflux precipitation copolymerization of zwitterionic sulfobetaine methacrylate(SBMA)monomer and disulfide bond-containing crosslinker N,N’-bis(acryloyl)cystamine(BAC)without adding any surfactants.The stability,biodegradability,cellular uptake,blood circulation,immunogenic response,and accumulation in tumor tissues of these nanogels were investigated.Finally,the antitumor efficacy of doxorubicin-loaded nanogels and the safety of nanogels were evaluated.The results demonstrated that PSBMA nanogels was stable in 10 % FBS solution and displayed superior long circulation in blood and induced no immunogenic responses.At 48 h after the first injection,the blood retention of nanogles was still as high as 21.3 % ID/g and the second injection could not weaken the blood half time.More importantly,PSBMA nanogels could favorably accumulated in tumors(10.7 % ID/g)and ship the therapeutic agents to ensure high cytotoxicity to the tumor cells.The PSBMA-DOX group exhibited the strongest tumor growth inhibition efficacy among all the treatment groups,the tumor inhibition rate was 90% which was superior to free DOX.In situ TUNEL analysis demonstrated that the most cell apoptosis and the highest apoptotic rate of tumor cells were found in the PSBMA-DOX group which was also supportive of the excellent antitumor therapeutic effect.In conclusion,the biodegradable zwitterionic PSBMA nanogels with superior blood circulation time may provide a promising platform for effective anticancer therapy.