BiVO4/Fe3O4@polydopamine superparticles for tumor multimodal imaging and synergistic therapy

doi:10.1186/s12951-021-00802-x

. 2021 Mar 29;19(1):90.

doi: 10.1186/s12951-021-00802-x.

BiVO₄/Fe₃O₄@polydopamine superparticles for tumor multimodal imaging and synergistic therapy

Ze Wang^#¹, Guan Wang^#², Tingting Kang^#¹, Shuwei Liu¹, Lu Wang³, Haoyang Zou⁴, Yu Chong⁵, Yi Liu⁶

Affiliations

¹ State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012, People's Republic of China.
² Department of Gastroenterology, China-Japan Union Hospital, Jilin University, Changchun, 130033, People's Republic of China.
³ Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, People's Republic of China.
⁴ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130012, People's Republic of China. zzhhyy2004@126.com.
⁵ State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, People's Republic of China. chongyu@suda.edu.cn.
⁶ State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012, People's Republic of China. yiliuchem@jlu.edu.cn.

^# Contributed equally.

PMID: 33781296
PMCID: PMC8008624
DOI: 10.1186/s12951-021-00802-x

BiVO₄/Fe₃O₄@polydopamine superparticles for tumor multimodal imaging and synergistic therapy

Ze Wang et al. J Nanobiotechnology. 2021.

. 2021 Mar 29;19(1):90.

doi: 10.1186/s12951-021-00802-x.

Authors

Ze Wang^#¹, Guan Wang^#², Tingting Kang^#¹, Shuwei Liu¹, Lu Wang³, Haoyang Zou⁴, Yu Chong⁵, Yi Liu⁶

Affiliations

¹ State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012, People's Republic of China.
² Department of Gastroenterology, China-Japan Union Hospital, Jilin University, Changchun, 130033, People's Republic of China.
³ Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, People's Republic of China.
⁴ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130012, People's Republic of China. zzhhyy2004@126.com.
⁵ State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, People's Republic of China. chongyu@suda.edu.cn.
⁶ State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012, People's Republic of China. yiliuchem@jlu.edu.cn.

^# Contributed equally.

PMID: 33781296
PMCID: PMC8008624
DOI: 10.1186/s12951-021-00802-x

Abstract

Background: Despite tremendous progress has been achieved in tumor theranostic over the past decade, accurate identification and complete eradication of tumor cells remain a great challenge owing to the limitation of single imaging modality and therapeutic strategy.

Results: Herein, we successfully design and construct BiVO₄/Fe₃O₄@polydopamine (PDA) superparticles (SPs) for computed tomography (CT)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging and radiotherapy (RT)/photothermal therapy (PTT) synergistic therapy toward oral epithelial carcinoma. On the one hand, BiVO₄ NPs endow BiVO₄/Fe₃O₄@PDA SPs with impressive X-ray absorption capability due to the high X-ray attenuation coefficient of Bi, which is beneficial for their utilization as radiosensitizers for CT imaging and RT. On the other hand, Fe₃O₄ NPs impart BiVO₄/Fe₃O₄@PDA SPs with the superparamagnetic property as a T₂-weighted contrast agent for MR imaging. Importantly, the aggregation of Fe₃O₄ NPs in SPs and the presence of PDA shell greatly improve the photothermal conversion capability of SPs, making BiVO₄/Fe₃O₄@PDA SPs as an ideal photothermal transducer for PA imaging and PTT. By integrating advantages of various imaging modalities (CT/PA/MR) and therapeutic strategies (RT/PTT), our BiVO₄/Fe₃O₄@PDA SPs exhibit the sensitive multimodal imaging feature and superior synergistic therapeutic efficacy on tumors.

Conclusions: Since there are many kinds of building blocks with unique properties appropriating for self-assembly, our work may largely enrich the library of nanomateirals for tumor diagnosis and treatment.

Keywords: BiVO4 nanoparticles; Fe3O4 nanoparticles; Multimodal imaging; Superparticles; Synergy therapy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
TEM and HRTEM characterizations of BiVO₄ NPs, Fe₃O₄ NPs, BiVO₄/Fe₃O₄ SPs and BiVO₄/Fe₃O₄@PDA SPs. TEM images of (a) BiVO₄ NPs, (b) Fe₃O₄ NPs, (c) BiVO₄/Fe₃O₄ SPs and (d) BiVO₄/Fe₃O₄@PDA SPs. Inset in (a) and (b): size distributions and HRTEM images of BiVO₄ and Fe₃O₄ NPs. Inset in (c) and (d): size distributions of BiVO₄/Fe₃O₄ SPs and BiVO₄/Fe₃O₄@PDA SPs

**Fig. 2**
Photothermal conversion capability characterizations of BiVO₄/Fe₃O₄@PDA SPs. Temperature increments vs. the proportions of Fe₃O₄ in BiVO₄/Fe₃O₄@PDA SPs (200 µg/mL SPs; 1 W/cm² irradiation) (a), the power densities of incident laser (200 µg/mL BiVO₄/Fe₃O₄-2@PDA SPs) (b), the concentrations of SPs (BiVO₄/Fe₃O₄-2@PDA SPs; 1 W/cm² irradiation) (c). The molar ratios of BiVO₄:Fe₃O₄ in SPs from BiVO₄/Fe₃O₄-1 to BiVO₄/Fe₃O₄-3 are 10.5:1, 5.4:1 and 3.6:1

**Fig. 3**
CT/MRI/PA imaging properties of BiVO₄/Fe₃O₄@PDA SPs in vitro and in vivo. a In vitro CT images and HU values of BiVO₄/Fe₃O₄@PDA SPs and iobitridol solution at different concentrations. b In vitro T₂-weighted MR images and T₂ relaxation rates of BiVO₄/Fe₃O₄@PDA SPs at different concentrations. c In vitro PA images and PA values of BiVO₄/Fe₃O₄@PDA SPs at different concentrations. In vivo CT (d), MR (e) and PA (f) images of mice bearing KB tumors obtained before and after intratumoral injection of BiVO₄/Fe₃O₄@PDA SPs

**Fig. 4**
Synergistic cancer treatment properties of BiVO₄/Fe₃O₄@PDA SPs in vitro. a Clonogenic assay of KB cells under different treatments (NIR: 0.33 W/cm² and 10 min; X-ray: 6 Gy). b Survival fraction of KB cells under different treatments (NIR: 0.33 W/cm² and 10 min; X-ray: 6 Gy). c Survival fraction of KB cells under different treatments and X-ray dose. d ROS production in KB cells under different treatments (scale bar is 200 µm). e γ-H2AX staining in KB cells under different treatments (scale bar is 40 µm). P-values were calculated by one-way ANOVA: *P < 0.05, **P < 0.01

**Fig. 5**
Synergistic cancer treatment properties of BiVO₄/Fe₃O₄@PDA SPs in vivo. Mice are randomly divided into 7 groups with 5 mice in each group. a Relative tumor volume curves of mice during 16 d. b Average tumor weights at the end of treatment. c Tumor photographs at the end of treatment. d Body weight curves of mice during 16 d. e Photographs of mice at the end of treatment. f H&E staining of tumor at the end of treatment (scale bar is 50 µm). P-values were calculated by one-way ANOVA: *P < 0.05, **P < 0.01

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References

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[1] Bernier J, Hall EJ, Giaccia A. Radiation oncology: a century of achievements. Nat Rev Cancer. 2004;4:737–47. doi: 10.1038/nrc1451. - DOI - PubMed

[2] Bernier J, Hall EJ, Giaccia A. Radiation oncology: a century of achievements. Nat Rev Cancer. 2004;4:737–47. doi: 10.1038/nrc1451. - DOI - PubMed

[3] Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer. 2008;8:545–54. doi: 10.1038/nrc2419. - DOI - PubMed

[4] Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer. 2008;8:545–54. doi: 10.1038/nrc2419. - DOI - PubMed

[5] Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer R. 2016;5:288–300. doi: 10.21037/tlcr.2016.06.07. - DOI - PMC - PubMed

[6] Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer R. 2016;5:288–300. doi: 10.21037/tlcr.2016.06.07. - DOI - PMC - PubMed

[7] Weichselbaum RR, Liang H, Deng L, Fu Y. Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol. 2017;14:365–79. doi: 10.1038/nrclinonc.2016.211. - DOI - PubMed

[8] Weichselbaum RR, Liang H, Deng L, Fu Y. Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol. 2017;14:365–79. doi: 10.1038/nrclinonc.2016.211. - DOI - PubMed

[9] Atun R, Jaffray DA, Barton MB, Bray F, Baumann M, Vikram B, Hanna TP, Knaul FM, Lievens Y, Lui TYM, Milosevic M, O’Sullivan B, Rodin DL, Rosenblatt E, Van DJ, Yap ML, Zubizarreta E, Gospodarowicz M. Expanding global access to radiotherapy. Lancet Oncol. 2015;16:1153–86. doi: 10.1016/S1470-2045(15)00222-3. - DOI - PubMed

[10] Atun R, Jaffray DA, Barton MB, Bray F, Baumann M, Vikram B, Hanna TP, Knaul FM, Lievens Y, Lui TYM, Milosevic M, O’Sullivan B, Rodin DL, Rosenblatt E, Van DJ, Yap ML, Zubizarreta E, Gospodarowicz M. Expanding global access to radiotherapy. Lancet Oncol. 2015;16:1153–86. doi: 10.1016/S1470-2045(15)00222-3. - DOI - PubMed

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BiVO₄/Fe₃O₄@polydopamine superparticles for tumor multimodal imaging and synergistic therapy

Affiliations

BiVO₄/Fe₃O₄@polydopamine superparticles for tumor multimodal imaging and synergistic therapy

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