Width-Consistent Mesoporous Silica Nanorods with a Precisely Controlled Aspect Ratio for Lysosome Dysfunctional Synergistic Chemotherapy/Photothermal Therapy/Starvation Therapy/Oxidative Therapy
journal contributionposted on 19.05.2020, 13:05 by Junna Lu, Fengyu Liu, Hongjuan Li, Yongqian Xu, Shiguo Sun
Although differently shaped mesoporous silica is widely studied, the formation of width-consistent mesoporous silica nanorods (MSNRs) with a precisely controlled aspect ratio (AR: length/width) is challenging and has not been reported. Herein, width-consistent (100 nm) MSNRs with ARs of 2, 3, 4, 6, 8, and 10 were obtained by increasing the concentrations while maintaining the molar ratio of cetyltrimethylammonium bromide (CTAB) and tetraethyl orthosilicate (TEOS). The results demonstrated that the as-prepared MSNR with an AR of 6 (AR6) possesses high cellular-uptake efficiency and drug-loading capacity. Thus, AR6-based cancer-cell-targeting nanosystems were designed. These nanosystems encapsulated doxorubicin (DOX) into the porous channel of AR6, adsorbed glucose oxidase (GOx), and then formed a polydopamine (PDA) layer for Siramesine (Siram, a lysosome dysfunctional drug) adsorption and folic acid modification. In this design, the PDA shell could prevent the leakage of loading components and keep the activity of GOx during delivery while achieving an on-demand drug release in the targeted location and photothermal therapy under near-infrared irradiation. The increase in temperature was highly beneficial for elevating the catalytic efficiency of GOx, accelerating the consumption of intracellular glucose, and generating a relatively high level of cytotoxic H2O2, all of which enhanced starvation and oxidative therapies. Siram was employed to inhibit lysosomal metabolism and accompany GOx to reach a dual-enhanced starvation therapy effect. In addition, DOX entered the nucleus and altered DNA for chemotherapy. The results showed that the nanosystems have superior therapeutic efficacy against cancer cells and not much toxicity to normal cells. Therefore, this study provides a novel strategy for lysosome dysfunctional synergistic chemotherapy/photothermal therapy/starvation therapy/oxidative therapy based on MSNR.
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near-infrared irradiationlysosome dysfunctionalTEOSPDA shellWidth-Consistent Mesoporous Silica Nanorodsintracellular glucoseDOXdual-enhanced starvation therapy effectCTABoxidative therapiesas-prepared MSNRnovel strategyAR 6-based cancer-cell-targeting nanosystemsphotothermal therapycytotoxic H 2 O 2loading componentson-demand drug releasefolic acid modificationtetraethyl orthosilicatecancer cellsmesoporous silicaglucose oxidaseTherapydrug-loading capacityDNAlysosomal metabolismwidth-consistent mesoporous silica nanorodscetyltrimethylammonium bromidecellular-uptake efficiencylysosome dysfunctional drugControlled Aspect Ratioaspect ratiomolar ratioGOxnanosystems encapsulated doxorubicin