Design, synthesis and investigation of a targetedtransport system composed of mesoporous silica nanoparticlesfor in vitro and in vivo delivery of oxaliplatin tocolorectal cancer cells

Background: A major challenge in successful cancer chemotherapyis achieving specific drug accumulation at the tumorsite. Due to the lack of specification and solubility of many drugmolecules, patients must take large doses to obtain the therapeuticeffects needed to treat the disease. The development of Smartnano carrier-based drug delivery systems has resulted from thenonspecific distribution and uncontrollable release of drugs inconventional drug delivery systems (CDDSs). Mesoporous silicananoparticle (MSN) has emerged as a promising candidateto overcome some problems. Due to their unique and biocompatiblestructure, MSNs ensure controlled and sustainable drugrelease and can be modified for targeted drug delivery. For thisaim, we used aptamer-conjugated nanoparticles against epcampositivecells for active targeting.Materials and Methods: Initially, the colorectal anticancerdrug, oxaliplatin, was loaded in MSNs, and its release at thephysiological pH was blocked via the gold gatekeepers. Polyethyleneglycol was used to increase the biocompatibility ofnanoparticles in blood circulation. Moreover, EpCAM aptamerwas used for the selective delivery of oxaliplatin to colorectalcancer cells (HT-۲۹). The in vitro tests performed include cellularinternalization, MTT assay, and evaluation of the cell deathmechanism. Tumor-inhibitory effects of the NPs were also examinedin vivo on immunocompromised female C۵۷BL/۶ mice.Results: The results indicated that the targeted nanocarrierscontaining the aptamer had high cytotoxicity and cellular uptakein colorectal cancer cells (HT-۲۹) compared to the Ep-CAM-negative CHO cells. The in vivo results in the C۵۷BL/۶mouse model bearing CRC also demonstrated that the targetednanocarrier could increase oxaliplatin accumulation in the tumorsite and reduced tumor growth compared to the control andnon-targeted nanocarrier.Conclusion: A targeted nanocarrier platform based on MSNs which can effectively deliver oxaliplatin to human CRC cells,can increase anticancer effects while reducing the side effects.

کلیدواژه ها:

CRC ، CDDSs ، Aptamer ، MSNs ، ph-sensitivegatekeeper