Development of stimuli-responsive nanoprobes with the aim of enabling targeted magnetic resonance imaging and drug delivery for ovarian cancer cells
Objective To fabricate nanoprobes consisting of tumor microenvironment stimuli-responsive mesoporous silicon dioxide@doxorubicin@manganese dioxide(mSiO2@DOX@MnO2)and assess their efficacy in terms of MRI and drug release in ovarian cancer cells.Methods The preparation of MnO2 involved ultrasonic disperion with transferrin serving as both a stabilizer and a targeted agent.The mSiO2@DOX@MnO2 nanoprobes were synthesized through electrostatic interaction utilizing MnO2 nanosheets as a gate.The nanoprobes were subsequently characterized for zeta potential,morphology,drug release kinetics,optical properties,and MRI properties.The cytotoxicity of the nanocomplexes was assessed against HO-8910 ovarian cancer cells and CHO hamster ovarian cells using the cell counting Kit-8(CCK-8)assay.The drug release within tumor cells was investigated using a confocal laser scanning microscope.Furthermore,the MRI imaging effect of the nanoprobes on HO-8910 cells was evaluated.Statistical analysis was performed using one-way analysis of variance and the LSD test.Results The mSiO2@DOX@MnO2 nanoprobes exhibited minimal magnetic resonance signal and a low drug release rate(less than 10%)in a normal physiological microenvironment.However,in the presence of glutathione(GSH),a strong T1 weighted signal was obseved,with a T1 relaxation efficiency of 5.86 mmol/(L·s).It could be observed that in an acidic environment with a pH of 5.0,the release rate of DOX reaches a relatively stable level at approximately 15 h,maintaining around 33%.Under the same condition with a pH of 7.4,the high concentration group exhibits significantly higher GSH release rate compared to the low concentration group,reaching about 55%.The highest release rate is achieved when both pH and GSH concentration are set at 5.0 and 10 mmol/L respectively,reaching up to 80%.The mSiO2@DOX@MnO2 nanoprobe demonstrates potent toxicity against tumor cells while exhibiting minimal toxicity towards normal CHO cells at experimental concentrations.When the DOX content in the mSiO2@DOX@MnO2 nanocomplex was about 100 μg/mL,HO-8910 cell survival rate is only about 24%,whereas CHO cell survival rate remains around 86%.Cell cytotoxicity tests demonstrated significant differences in the survival rates of HO-8910 cells and CHO cells when treated with varying concentrations of mSiO2@DOX@MnO2(P<0.05).When the concentration of manganese ions was 1.12 mmol/L,the T1 relaxation time of the HO-8910 cell group was 467.60±4.45 ms,while that of the CHO cell group was 1681.47±1.88 ms.The T1 values of the HO-8910 cells and CHO cells groups showed significant differences when treated with equivalent concentrations of mSiO2@DOX@MnO2(P<0.05).Conclusion The developed mSiO2@DOX@MnO2 nanoprobe exhibits targeted identification and localization capabilities towards ovarian cancer cells,enabling T1-weighted imaging and precise drug release in acidic tumor microenvironments with high levels of GSH stimulation response,thereby facilitating targeted magnetic resonance imaging and treatment at the cellular level for ovarian cancer.
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