Supporting Information (SI) for: Renal Clearable Peptide Functionalized NaGdF 4 Nanodots for. High-Efficiency Tracking Orthotopic Colorectal Tumor in

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1 Supporting Information (SI) for: Renal Clearable Peptide Functionalized NaGdF 4 Nanodots for High-Efficiency Tracking Orthotopic Colorectal Tumor in Mouse Hongda Chen, a,c Xiaodong Li, b Fuyao Liu, a Huimao Zhang*,b and Zhenxin Wang*,a a State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, , P. R. China. wangzx@ciac.ac.cn (ZW); Fax: (+86) b Department of Radiology, the First Hospital of Jilin University, Changchun , P. R. China huimaozhanglinda@163.com. c University of Chinese Academy of Sciences, Beijing , P. R. China 1 Additional Experimental Section 2 Additional Figures S1-S12 3 Additional Table S1-S3 4 Additional References

2 1 Additional Experimental Section Synthesis of oleate-capped NaGdF 4 Nanodots: The oleate-capped NaGdF 4 Nanodots were synthesized according to a previously reported method with slight modifications. S1-S3 Typically, 0.5 ml GdCl 3 (1.6 M) aqueous solutions were injected in a 100 ml flask, and dried by heating. Then, oleic acid (4 ml) and 1-octadecene (15 ml) were added into the flask. The mixture was heated to 150 C under argon atmosphere to obtain a homogeneous solution. After cooling to 50 C, a methanol solution (10 ml) containing NH 4 F (3 mmol) and NaOH (2.5 mmol) was slowly added into the solution and stirred overnight. And then the methanol was evaporated and the solution was degassed for 10 min. Subsequently, the temperature of the mixture was increased to 250 C at a rate of 10 C min -1 and maintained at 250 C for 10 min under argon protection. After cooling to room temperature, the as-prepared NaGdF 4 Nanodots were collected by centrifugation (10000 rpm for 10 min), and washed with ethanol (10 ml, three times). Finally, the NaGdF 4 Nanodots were redispersed in cyclohexane (10 ml).

3 2 Additional Figures S1-S9 Figure S1 XPS survey spectra of hydrophobic oleate-nagdf 4 nanodots (a) and hydrophilic ppeptide-nagdf 4 nanodots (b).

4 Figure S2 EDS analysis of hydrophobic oleate-nagdf 4 nanodots (black line) and hydrophilic ppeptide-nagdf 4 nanodots (red line), respectively.

5 Figure S3 FTIR spectra of hydrophobic oleate-nagdf 4 nanodots (black line) and hydrophilic ppeptide-nagdf 4 nanodots (red line), respectively.

6 Figure S4. TGA curves of ppeptide-nagdf 4 nanodots and tryptone-nagdf 4 nanodots.

7 Figure S5. The HDs of ppeptides-nagdf4 nanodots in the PBS with different ph values. The HDs are 11.7 ± 1.3, 10.1 ± 1.2, 7.5 ± 0.6, and 8.7 ± 0.5 for ph 5.0, 6.0, 7.0 and 8.0, respectively.

8 Figure S6 Digital photographs of 1 mg ml -1 ppeptide-nagdf 4 nanodots in different dispersing media including water (a), PBS (ph=7.4, b), 0.9% NaCl solution (c) and DMEM supplemented with 10% FBS (d), respectively.

9 Figure S7 The relative viabilities of SW620 cells as a function of the concentrations of ppeptide-nagdf 4 nanodots in culture medium. Error bars mean standard deviations (n = 5).

10 Figure S8 The histology analysis of drug induced orthotopic colorectal tumor.

11 Figure S9 (a) In vivo MR images of BALB/C mouse bearing drug induced orthotopic colorectal tumor after intravenous injection of tryptone-nagdf 4 nanodots (10 mg Gd kg -1 body) at different timed intervals (pre-injection (0), 1, 2, and 24 h post-injection), respectively. (b) Digital photograph of the rectum with tumor. (c) Corresponding data analysis of MR measurements. The tumor site was marked by circle. Error bars mean standard deviations (n = 5).

12 Figure S10 (a) In vivo MR images of BALB/C mouse bearing drug induced orthotopic colorectal tumor after intravenous injection of ppeptide-nagdf 4 nanodots (2.0 mg Gd kg -1 body) at different timed intervals (pre-injection (0), 1, 2, and 24 h post-injection), respectively. (b) Digital photograph of the rectum with tumor. (c) Corresponding data analysis of MR measurements. The tumor site was marked by circle. Error bars mean standard deviations (n = 5).

13 Figure S11 TEM micrograph of ppeptide-nagdf 4 nanodots which were found in the mouse urine.

14 Figure S12 Biodistribution of Gd element in main organs of mice. The organs of mice bearing drug induced orthotopic colorectal tumor were harvested at 1, 2 and 24 h post-intravenous injection of ppeptide-nagdf 4 nanodots. As a control, the organs of health mice were harvested at 24 h post-intravenous injection of ppeptide-nagdf 4 nanodots. The concentration of ppeptide-nagdf 4 nanodots is 10 mg Gd kg -1 body.

15 3 Additional Table S1-S3 Table S1 The HD and Zeta potential of ppeptides-nagdf 4 nanodots with different dispersants. Dispersant Zeta potential (mv) HD (nm) Water 8.24 ± ± 0.1 PBS 7.32 ± ± % NaCl solution 9.45 ± ± 2.0 DMEM with 10% FBS ± ± 2.3 The ppeptides-nagdf 4 nanodots have negative surface charge and relative large HD in DMEM with 10% FBS because the ppeptides-nagdf 4 nanodots can interact with proteins in FBS.

16 Table S2 The blood hematology analysis of healthy mouse at 30 day post-injection of a single dose of ppeptide-nagdf 4 nanodots (Gd content: 10 mg kg -1 body) in NaCl solution (0.9 wt%). Hematological Units Control Treatment WBC 10 9 /L 9.38 ± ± 0.69 RBC /L 9.77 ± ± 0.98 HGB g/l ± ± MCV fl ± ± 6.74 MCH pg ± ± 1.84 MCHC g/l ± ± PLT 10 9 /L ± ± PDW fl ± ± 0.82

17 Table S3 The blood biochemical assay of healthy mouse at 30 day post-injection of a single dose of ppeptide-nagdf 4 nanodots (Gd content: 10 mg kg -1 body) in NaCl solution (0.9 wt%). Biochemistry Units Control Treatment AST U/L ± ± 15.8 ALT U/L 44.7 ± ± 7.2 TP g/l 73.5 ± ± 5.7 BUN mmol/l 7.24 ± ± 0.84 CRE μmol/l 36.8 ± ± 3.86

18 4 Additional References S1. N. J. J. Johnson, W. Oakden, G. J. Stanisz, R. S. Prosser and F. C. J. M. van Veggel, Chem. Mater., 2011, 23, S2. F. Liu, X. He, J. Zhang, H. Zhang and Z. Wang, Small, 2015, 11, S3. H. Xing, S. Zhang, W. Bu, X. Zheng, L. Wang, Q. Xiao, D. Ni, J. Zhang, L. Zhou, W. Peng, K. Zhao, Y. Hua and J. Shi, Adv. Mater., 2014, 26,