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Peer-reviewedCC BYCancer Nanotechnology

Tumor-targeted nanobubbles delivering PFP/siFGFR1 for US imaging and overcoming enzalutamide-resistant in prostate cancer

  • Weimin Dong1
  • Zhiming Zhang1
  • Zhengming Su1
  • Henghui Zhang1
  • Yiqiao Huang1
  • Guohao Zeng1
  • Maozhi Xiao1
  • Kaiyue Tang1
  • Weide Zhong2
  • Xianhan Jiang1
  1. 1Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University
  2. 2Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First Peoples Hospital, School of Medicine, South China University of Technology
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Abstract

Enzalutamide (ENZ) resistance has emerged as a critical therapeutic hurdle in advanced prostate cancer (PCa) management. This study aims to investigate the potential of ultrasound-guided nanobubble-mediated co-delivery of small interfering RNA targeting fibroblast growth factor receptor 1 (siFGFR1) and ENZ to overcome ENZ resistance in PCa. The nanobubbles (PFP-ENZ@siRNA-NBs-RGD) were characterized for particle size, zeta potential, and morphology. Their biocompatibility was confirmed via hemolysis assays. In vitro, selective targeting of PCa cells was observed, and the system exhibited minimal toxicity to normal cells while effectively inhibiting ENZ-resistant PCa. Under ultrasound, ENZ and siFGFR1 downregulated AR/PSA, p-PI3K/p-Akt/p-mTOR and P-gp, and modulated apoptotic-related proteins (Caspase-3/Bax upregulated, Bcl-2 downregulated). Additionally, apoptosis rates were significantly increased. In vivo, tumor growth was reduced, with concurrent suppression of p-PI3K/p-Akt/p-mTOR, P-gp downregulation, and apoptotic-related protein modulation in tumor tissues, validating in vitro mechanisms. Moreover, no adverse effects were observed. These findings suggest that the ultrasound-guided co-delivery of siFGFR1 and ENZ via nanobubbles represents a promising strategy to combat ENZ-resistant prostate cancer.

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Cite

BibTeXRIS
BibTeX
@article{dong2026tumortargeted,
  title = {{Tumor-targeted nanobubbles delivering PFP/siFGFR1 for US imaging and overcoming enzalutamide-resistant in prostate cancer}},
  author = {Weimin Dong and Zhiming Zhang and Zhengming Su and Henghui Zhang and Yiqiao Huang and Guohao Zeng and Maozhi Xiao and Kaiyue Tang and Weide Zhong and Xianhan Jiang},
  journal = {Cancer Nanotechnology},
  year = {2026},
  month = jul,
  doi = {10.1186/s12645-026-00409-7},
  url = {https://doi.org/10.1186/s12645-026-00409-7},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Tumor-targeted nanobubbles delivering PFP/siFGFR1 for US imaging and overcoming enzalutamide-resistant in prostate cancer
AU  - Weimin Dong
AU  - Zhiming Zhang
AU  - Zhengming Su
AU  - Henghui Zhang
AU  - Yiqiao Huang
AU  - Guohao Zeng
AU  - Maozhi Xiao
AU  - Kaiyue Tang
AU  - Weide Zhong
AU  - Xianhan Jiang
PY  - 2026
DA  - 2026/07/01
JO  - Cancer Nanotechnology
DO  - 10.1186/s12645-026-00409-7
UR  - https://doi.org/10.1186/s12645-026-00409-7
AB  - Enzalutamide (ENZ) resistance has emerged as a critical therapeutic hurdle in advanced prostate cancer (PCa) management. This study aims to investigate the potential of ultrasound-guided nanobubble-mediated co-delivery of small interfering RNA targeting fibroblast growth factor receptor 1 (siFGFR1) and ENZ to overcome ENZ resistance in PCa. The nanobubbles (PFP-ENZ@siRNA-NBs-RGD) were characterized for particle size, zeta potential, and morphology. Their biocompatibility was confirmed via hemolysis assays. In vitro, selective targeting of PCa cells was observed, and the system exhibited minimal toxicity to normal cells while effectively inhibiting ENZ-resistant PCa. Under ultrasound, ENZ and siFGFR1 downregulated AR/PSA, p-PI3K/p-Akt/p-mTOR and P-gp, and modulated apoptotic-related proteins (Caspase-3/Bax upregulated, Bcl-2 downregulated). Additionally, apoptosis rates were significantly increased. In vivo, tumor growth was reduced, with concurrent suppression of p-PI3K/p-Akt/p-mTOR, P-gp downregulation, and apoptotic-related protein modulation in tumor tissues, validating in vitro mechanisms. Moreover, no adverse effects were observed. These findings suggest that the ultrasound-guided co-delivery of siFGFR1 and ENZ via nanobubbles represents a promising strategy to combat ENZ-resistant prostate cancer.
SN  - 1868-6958
SN  - 1868-6966
ER  -