Study On Molecularly Imprinted Nanoparticles-based Cancer Targeted Therapy

As one of the diseases with the heighest morbidity and mortality rate in the world,cancer seriously threatens human life and health.At present,the clinical treatment of cancer mainly includes surgical treatment,chemotherapy and radiotherapy.Chemotherapy and radiotherapy,which are not specific to tumor,can cause serious damage to normal tissues and cells while killing cancer cells,so the effectiveness of cancer treatment is severely restricted by the serious toxicity and side effects of these two therapies.Tumor targeted therapy using therapeutic agents which can specifically target tumors and then kill cancer cells or targeted drug carriers which can deliver chemotherapeutic or radiotherapeutic drugs to tumors.The proposed treatment method breaks the limitations of traditional cancer treatment methods and provides new possibilities for precise treatment of cancer.Nowadays,targeted cancer therapy mainly relies on antibodies,aptamers and peptides.However,these biomacromolecules generally have some obvious shortcomings,such as difficulty in preparation,poor stability and high price,which limit their application in targeted cancer therapy.Therefore,there is an urgent need to develop new tumor targeted therapy materials which can overcome these shortcomings.Molecularly imprinted polymers(MIPs)have shown great potential in targeted cancer therapy due to their high affinity and selectivity to target molecules.On the other hand,they are easy to prepare,stable in nature and low cost However,the application of molecularly imprinted polymers in the field is still in its infancy,and new research results are urgently needed to prove its application value.In recent years,our group has developed a series of universal and convenient boronate affinity molecular imprinting methods based on boronate affinity molecular imprinting technology,which has been successfully applied to the recognition and detection of glycoproteins and saccharides.Among them,the boronate affinity-based controllable oriented surface imprinting method developed by our group can adjust the thickness of imprinting layer by controlling the imprinting time.In addition,the molecular imprinted polymers prepared by using glycoprotein’s characteristic glycans or epitope peptides as imprinting templates can specifically recognize glycoproteins and their characteristic fragments.Combine the boronate affinity molecular imprinting technology developed by our group and fluorescence imaging technology together,we designed some novel molecularly imprinted polymers which can be used for targeted imaging and therapy of cancer.Firstly,we present molecularly imprinted nanoparticles that can block the HER2 signaling pathway and thereby inhibit the growth of HER2 positive breast cancer.The molecularly imprinted nanoparticles(NPs)were prepared using glycans of HER2 as imprinting templates.The NPs can specifically recognize HER2 positive breast cancer by binding the glycans of HER2,but has no significant binding effect on other HER2 negative cells.Meanwhile,because of their bigger size as compared with the EGFR members,once binding with HER2,the glycan-imprinted NPs will block the dimerization of HER2 with other EGFR members due to steric hindrance,resulting in blocking of the downstream signaling pathways and thereby inhibition of the growth of HER2 positive breast cancer.Both experiments at the cell level and the animal level indicated that the glycan-imprinted NPs can specifically target HER2 and inhibit the growth of HER2 positive cancer.The work provids strong evidence for the application of MIPs in the field of targeted cancer therapy,and further demonstrats the important potential of MIPs in the field of targeted cancer therapy.In another work,we constructed a tumor targeted drug delivery system based on boronate affinity oritend surface imprinting technology.Sialic acid(SA)which was overexpressed on most of cancer cell membrane and 5’-deoxy-5-fluorocytidine(5’-DFCR)which was intermediate of capecitabine and can be converted into active drug 5-fluorouracil in cells were chosen as dual templates in imprinting process.The obtained MIPs can deliver the drugs to SA overexpress ed cancer cells and release the drugs in slightly acidic tumor environment.The tumor targeted drug delivery system will reduce the toxicity and side effects of chemotherapeutic drugs,having important application prospects in cancer targeted therapy.