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. 2023 Jan 19:18:339-351.
doi: 10.2147/IJN.S387409. eCollection 2023.

The Combined Effect of Nanobubble-IR783-HPPH-Affibody Complex and Laser on HER2-Positive Breast Cancer

Wenbin Cai #  1   2 , Wei Lv #  1   3 , Li Meng  2 , Yunyou Duan  1 , Li Zhang  1
Affiliations

The Combined Effect of Nanobubble-IR783-HPPH-Affibody Complex and Laser on HER2-Positive Breast Cancer

Wenbin Cai et al. Int J Nanomedicine. .

Abstract

Introduction: Nanobubble is an innovative ultrasound contrast agent that triggers the development of targeted imaging of HER2-positive breast cancer by combining with HER2 affibody and IR783. HPPH is a second-generation photosensitiser that is effective in treating tumours. Hence, the nanobubble-IR783-HPPH-affibody (NIHA) complex demonstrates considerable potential in the treatment of HER2-positive breast cancer.

Methods: We fabricated the NIHA complex via an advanced thin-film hydration method and detected its characteristics such as particle size, morphology, stability, and cytotoxicity. Moreover, the effect of NIHA complex with laser on HER2-positive breast cancer was confirmed via in vitro and in vivo experiments.

Results: The NIHA complex was spheroid, stable and exhibited no cytotoxicity; moreover, its particle size was 524.8 ± 53.3 nm (n = 5). In combination with laser treatment, NIHA complex reduced the cell viability and tumour volume, induced apoptosis of HER2-positive breast cancer cells, and prolonged survival of nude mice.

Conclusion: The newly prepared NIHA complex with laser treatment has the potential on treating HER2-positive breast cancer.

Keywords: HER2; HPPH; breast cancer; laser; nanobubbles.

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Conflict of interest statement

The authors declare that they have no competing interests in this work.

Figures

Figure 1
Figure 1
Schematic diagram of the nanobubble-IR783-HPPH-affibody (NIHA) complex formation and behaviour in the tumour tissue. The NIHA complex penetrates the blood vessel of the tumour tissue and target specific HER2-positive cancer cells and killed the cancer cells via ROS effect under laser exposure.
Figure 2
Figure 2
The particle size of the nanobubble-IR783-HPPH complex (A) and the NIHA complex (B). (C) The TEM results of the NIHA complex. (D) The fluorescence microscopy image of the NIHA complex.
Figure 3
Figure 3
Stability and cytotoxicity. The diameter (A) and the concentration (B) stability of the NIHA complex at 4 °C (*P < 0.05 indicated statistically significant differences compared with those observed at 1 min). In vitro cytotoxicity for various concentrations of HPPH (C) and IR783 (D) determined by using the CCK-8 assay (*P < 0.05 indicates statistically significant differences compared with normal cells).
Figure 4
Figure 4
The targeting ability of the NIHA complex. The CLSM images of BT-474 cells incubated with the NIHA complex (up) and the nanobubble-Dil-HPPH complex (down). Bar, 50 μm.
Figure 5
Figure 5
(A) Cell viability of BT-474 cells detected via CCK-8. (B) The apoptotic ratio of BT-474 cells detected via Annexin-V flow cytometry. **P < 0.01 compared with the NIHA-laser group.
Figure 6
Figure 6
CLSM images of BT-474 cells in the NIHA-laser, NIHA, laser, and the control groups. The nuclei of the apoptosis cells were stained by using PI (depicted as red fluorescence). Bar, 30 μm.
Figure 7
Figure 7
(A) The NIRF imaging of xenografts in nude mice after injection of the NIHA complex. (B) The ultrasound contrast-enhanced imaging of xenografts in nude mice before and after injection of the NIHA complex.
Figure 8
Figure 8
In vitro fluorescence imaging of the tumour, heart, liver, spleen, lung, kidney, and lymph at different time points after NIHA complex injection.
Figure 9
Figure 9
Tumour growth inhibition and cumulative survival of mice assessed in various treatment groups. (A) Tumour volume growth of each group. (B) The cumulative survival of mice in each group.
Figure 10
Figure 10
H&E assay performed for the sections of tumour, heart, kidney, liver, spleen, and lung in the five different groups. Bar, 100 μm.
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