Study Of Multiple Responsive Magnetic-targeted Nanoparticles For Controlled Drug Release

Active and effective treatment for diseases is the major goal of mankind over the past 2,000 years.In the past sixty years,the multifunctional drug delivery system has been a hot topic in the biomedical field.The nanocarriers have the characteristics of controllable and modifiable structure,which can be used to modify the carrier for various purposes to achieve high therapeutic effect.For example:monitoring the treatment process,increasing water-solubility of hydrophobic drugs,reducing the leakage of drugs in the systemic circulation process,increasing the specific accumulation of drugs in organs or cells,etc.At present,the controlled release of drugs can be achieved by modifying environmental stimuli responsiveness on the nanocarrier.However,how to improve the curative effect,reduce the toxic and side effects of drugs,and reduce the drug resistance caused by repeated use of drugs are still problems to be solved in nanocarriers.Therefore,we have designed two nanocarriers.At first,a nanocarrier characteristic of acid induced charge reversal and acid/redox/magnetic combinational stimuli-responsiveness was designed.This system exhibits weaker repulsion between the carrier and the cancer cell membrane,resulting in enhanced uptake.After nanocarriers enter the cell,the system exhibits negative-to-positive charge reversal in response to the low intracellular pH value.Moreover,after the uptake,the carrier will be further dissociated by glutathione in cytoplasm via the reduction of the disulfide bond,leading to the rapid release of the encapsulated DOX into the nuclei.In vitro release study expressed the sequent stimulus release profile.The antitumor activity tested in CT26 tumor-bearing mice revealed efficient therapeutic efficacy and as low adverse effect as PBS.H&E staining and immunohistochemical analysis of tumor tissues as well as pathological test of tissue sections of vital organs confirmed the high antitumor activity and low tissue toxicity.Thus,the belief that this system has a good prospect in the field of cancer clinical chemotherapy.In addition,although the designed nanocarrier can help drug selectively release into cancer cells,repeated use of the drug can cause tumor cells to develop drug resistance.Once the drug resistance occurs,the chemotherapy effect of the drug obviously drops,which not only reduces the treatment effect but also causes the waste of the medicine and also brings more pain to the patient.Many studies indicated that selenium(Se)can increase the sensitivity of cancer cells to conventional anticancer drugs.Therefore,we introduced Se NPs into DOX-loaded D-P-MNPs to obtain Se@DOX-loaded D-P-MNPs to increase the sensitivity of cancer cells to DOX.A series of structural characterizations demonstrate that the successful addition of Se NPs.Compared with DOX-loaded D-P-MNPs,significant cytotoxicity improvement was observed in cells experiment due to the Se NPs.In summary,firstly,DOX-loaded D-P-MNPs was designed to improve the curative effect,reduce the toxic and side effects of drugs.Subsequently,in order to reduce the drug resistance and increase the availability of drugs,we developed Se@DOX-loaded D-P-MNPs.We believed that these two nanocarrier would provide some certain application value for the future study.