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Supplementry Informtion Lignd exchnge triggered controlled-relese trgeted drug delivery system sed on core shell superprmgnetic mesoporous microspheres cpped with nnoprticles Zhogng Teng, Xingng Zhu, Gengfeng Zheng, Fn Zhng, Yonghui Deng, Lichen Xiu, Wei Li, Qing Yng* nd Dongyun Zho* Deprtment of Chemistry, Shnghi Key Lortory of Moleculr Ctlysis nd Innovtive Mterils, Lortory of Advnced Mterils, Fudn University, Shnghi 2433, PR Chin. School of Life Sciences, Fudn University, 22 Hndn Rod, Shnghi 2433, PR Chin Emil: dyzho@fudn.edu.cn; yngqing68@fudn.edu.cn, Tel: 86-21-5163-25, Fx: 86-21-5163-37

1µm c 5 4 d 3 2 1 15 2 25 3 35 4 45 Dimeter (nm) Figure S1. SEM () nd TEM (, c) imges of mgnetite spheres nd the size distriution (d) of the spheres y mesuring out 15 prticles. The mgnetite prticles were synthesized y solvotherml rection. Briefly,.65 g of FeCl 3,.2 g of trisodium citrte dihydrte nd 1.2 g of sodium cette were dissolved in 2 ml of ethylene glycol under mgnetic stirring. The otined homogeneous yellow solution ws trnsferred to Teflon-lined stinless-steel utoclve with cpcity of ~ 3 ml. The utoclve ws heted to 2 C nd mintined for 1 h, nd then cooled down to room temperture. The otined lck mgnetite prticles were wshed with wter for 5 times, nd then dried in vcuum t 6 C for 12 h.

Electronic Supplementry Mteril (ESI) for Journl of Mterils Chemistry Figure S2. The SEM () nd TEM () imges of the core-shell Fe3O4@nSiO2 spheres prepred using conventionl Stöer method y dispersing the mgnetite Fe3O4 spheres in 5. ml of concentrted mmoni queous solution (25 wt %), 16 l of TEOS, 4 ml of ethnol, nd 1 ml of deionized wter. Figure S3. SEM () nd TEM () imges of the superprmgnetic mesoporous silic microspheres (SMMs) prepred y two-step coting procedures.

1 Intensity (.u.) 11 2 2 4 6 8 1 2 Thet (degree) Figure S4. Low-ngel XRD pttern of the superprmgnetic mesoporous microspheres. Asored Volume (cm 3 /g) 12 1 8 6 4 2..2.4.6.8 1. Reltive pressure(p/p ) dv/dd (cm 3 g -1 nm -1 ).12.1.8.6.4.2. 1 2 3 4 5 Pore dimeter (nm) Figure S5. Nitrogen dsorption-desorption isotherms () nd pore size distriution curves () of the superprmgnetic mesoporous silic microspheres (lck) nd SMM-IONP (red). The decrese of sorption volume t p/p =.3.7 nd the disppering of the mximum pek in pore size distriution plot indicte tht the mesopores of superprmgnetic mesoporous microspheres re cpped y the iron oxide nnoprticles. The hysteresis loop of SMM-IONP t p/p =.8 1 is ttriuted to the ccumultion of iron oxide nnoprticles on the surfces of microspheres.

c d Figure S6. TEM imges of the nnoprticles (Fe 3 O 4 ) detched from the drug delivery system y ddition of sodium citrte solution (2 mm) for 5 (); 1 (); nd 15 min (c). The nnoprticles Fe 3 O 4 detched from the drug delivery system surfce fter ddition of sodium citrte for 15 min (d). Mss (%) 12 1 98 96 94 92 9 1 2 3 4 5 Temperture ( o C) Figure S7. Thermogrvimetric (TG) curves of the iron oxide nnoprticles efore (), nd fter () modified with iminodicetic cid.

Electronic Supplementry Mteril (ESI) for Journl of Mterils Chemistry Mgnetiztion (emu/g) 8 6 4 Mgnetite SMM SMM-IONP 2-2 -4-6 -8-2 -1 1 2 Applied Mgnetic Field (Oe) Figure S8. Room-temperture mgnetiztion curves of the mgnetite Fe3O4 spheres, superprmgnetic mesoporous silic microspheres (SMMs), nd drug delivery system sed on superprmgnetic mesoporous microspheres cped with iron oxide nnoprticles (SMM-IONP). Insert is the photogrphs of the cptured drug delivery system y.4 T mgnet nd the redispersed system y slight shking fter removl of the mgnet. c Figure S9. Photogrphs of two ottles chrged with 15 mg of Rhodmine B-loded drug delivery system dispersed in 2. ml of PBS solution. (), The Rhodmine B-loded drug delivery system collected y externl mgnets; () fter the ddition of (.1 M) sodium citrte to the solution contined in the ottle on the right, pink fluorescence for 15 seconds. Showing relese of Rhodmine B from the encpsulted mtrix; (c) fter the ddition of sodium citrte to the solution for 1.5 h.

Tle S1. Mens, stndrd devitions, nd P-vlues of SGC-791 cells incuted with the superprmgnetic mesoporous silic microspheres (SMMs) nd drug delivery system (SMM-IONP) t different concentrtions for 1 ~ 16 h. control SMM SMSS SMM SMSS SMSS-NPs SMM-IONP 1 SMM-IONP SMSS-NPs.1 1µg/mL mg/ml 1µg/mL.1 mg/ml.1 µg/ml mg/ml 1µg/mL.1 mg/ml men 1 h 1.965.864.985.842 stndrd devition.16.111.79.5 P.61.83.765.7 men 12 h 1.924.836.967.84 stndrd devition.75.19.97.55 P.35.66.494.2 men 16 h 1.973.847.974.845 stndrd devition.13.18.42.64 P.658.37.399.3 Tle S2. Mens, stndrd devitions, nd P-vlues of PC12 cell incuted with the superprmgnetic mesoporous silic microspheres (SMM) nd drug delivery system (SMM-IONP) t different concentrtions for 6 ~ 12 h. control SMM SMSS SMM SMSS SMM-IONP SMSS-NPs SMM-IONP SMSS-NPs.1 1µg/mL mg/ml 1µg/mL.1 mg/ml.1 1µg/mL mg/ml.1 1µg/mL mg/ml men 6 h 1.923.73.89.712 Stndrd deviton.118.11.5.78 P.253.3.19. men 8 h 1.917.798.939.758 Stndrd deviton.71.68.39.13 P.218.14.353.11 men 12 h 1.937.75.899.772 Stndrd deviton.84.84.99.61 P.259.1.171.7

c d e f Figure S1. Fluorescence confocl microgrphs of HeL cells incuted with the rhodmine B-loded drug delivery system. The focl plne ws vried long the Z-xis from () the ottom to (f) the top of the cells. After incuted for 2 h, the microgrphs of the live cells with different focl depth long Z-xis show tht the rhodmine B-loded drug delivery system is indeed internlized y HeL cells.

c d e f Figure S11. Fluorescence confocl microgrphs of SGC-791 cells incuted with the rhodmine B-loded drug delivery system. The focl plne is vried long the Z-xis from () the ottom to (f) the top of the cells. After incuted for 2 h, the microgrphs of the live cells with different focl depth long Z-xis show tht the rhodmine B-loded drug delivery system is indeed internlized y SGC-791 cells.

1 Cell Viility (%) 8 6 4 2 5 1 15 pclitxel ( g/ml) 2 Figure S12. Viility of SGC-791 cells incuted with free pclitxel t different concentrtions.