Supplementary Material

Drug-loaded titanium dioxide nanoparticle coated with tumor targeting polymer as a

sonodynamic chemotherapeutic agent for anti-cancer therapy

Seonil Kima, Sooseok Imb, Eun-Yeong Parkc, Junseok Leea, Chulhong Kimd, Tae-il Kime,*, and

Won Jong Kima,*

a Department of Chemistry, Pohang University of Science and Technology (POSTECH),

Jigok-ro 64, Nam-gu, Pohang 37666, Republic of Korea

*Corresponding author

Email: wjkim@postech.ac.kr

b School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science

and Technology (POSTECH), Jigok-ro 64, Nam-gu, Pohang 37666, Republic of Korea

c Department of Electrical Engineering, Pohang University of Science and Technology

(POSTECH), Pohang, Republic of Korea

d Departments of Creative IT Engineering and Electrical Engineering, Pohang University of

Science and Technology (POSTECH), Pohang, Republic of Korea

e Department of Biosystems & Biomaterials Science and Engineering, College of Agriculture

and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826,

Republic of Korea

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O

OO O513

+BOH

OH

O

x

O

OHOOCHN

yCOOHO OH

H2N

BOH

HOPoly(methyl vinyl ether-alt-

maleic anhydride)(pMVMA)

3-aminophenylboronic acid

(PBA)

1. DMSO, 12 h

2. DIalysis

Poly(pheny boronic acid)(pPBA)

Figure S1. Synthetic procedure of poly(phenylboronic acid) (pPBA).

Figure S2. 1H-NMR spectra of pPBA The molar ratio of conjugated PBA was calculated by

1H NMR (yield: 93%). 1H NMR (Methanol-d4, 500 MHz): 1.6–2.3 (m, –CH2–, 2H); 2.8–3.2

(m, anhydride, 2H); 3.3-3.5 (m, –OCH3, 3H); 3.6–4.0 (m, –CH–, 1H); 7.0–7.8 (m, Ph, 4xH).

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Figure S3. FT-IR spectra of pPBA, pMVMA, and PBA-NH2.

Figure S4. (A) Schematic illustration of pMA@TNP-DOX and pPBA@TNP formation. (B)

DLS size measurement of pMA@TNP-DOX and pPBA@TNP.

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Figure S5. (A) Fluorescence spectra DOX and DOX-TNP with 1 mM DOX equivalence at

ex = 495 nm. (B) Fluorescence spectra of pPBA and pPBA@TNP-DOX with 1 mM PBA at

ex = 300 nm.

Figure S6. Zeta potential measurement of pPBA, TNP, TNP-DOX, and pPBA@TNP-DOX.

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Figure S7. Cytotoxicity of ultrasound irradiation in MCF-7 cell line and MDA-MB-231 cell

line (3 W·cm-2, 1.5 MHz, duty cycle: 20%) analysed by MTT assay.

Figure S8. Flow cytometry of MDA-MB-231 cell line treated with pPBA@TNP-DOX.

pPBA, pMA@TNP-DOX, and pPBA@TNP-DOX. For competition assay, pPBA@TNP-

DOX was co-incubated with PBA-NH2.

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Figure S9. Serum stability of bared TNP and pPBA@TNP-DOX.

DOXpP

BATNP

pPBA@

TNP-DOX

0

20

40

60

Hem

olys

is (%

)

Figure S10. Quantitative hemolysis assay using 1 mM DOX, pPBA, TNP, and pPBA@TNP-

DOX in vitro.

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Figure S11. Ex vivo DOX accumulation. Quantitative analysis of DOX content (total

fluorescence intensity of DOX from each organ) in each organ after treatment of free DOX,

pMA@TNP-DOX and pPBA@TNP-DOX (n=3, *P < 0.05).

Figure S12. Body weight changes of mice for 21 days.

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Figure S13. Representative tumor images at day 21 after i.v. injection

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