pH-Responsive Erdafitinib Liposomes with FGFR3 Targeting for Intravesical Bladder Cancer Therapy
- 1School of Biomedical Engineering, Fourth Military Medical University, Xi’an 710032, China
- 2Medical Innovation Center, Fourth Military Medical University, Xi’an 710032, China
- 3Department of Pharmaceutics and Pharmacy Administration, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China
Abstract
Fibroblast growth factor receptor 3 (FGFR3) is a key oncogenic driver in bladder cancer (BCa). Although erdafitinib, the pioneering FGFR3 inhibitor, is approved for clinic use, its oral administration frequently causes inadequate therapeutic effect and side effects. Here, we report a pH-responsive and erdafitinib-loaded liposomal nanosystem with surface modification of anti-FGFR3 antibodies (Phl-erda@Ab), which demonstrates improved antitumor effects in intravesical instillation therapy. In RT112 cells, we evaluated targeted uptake and antiproliferative activity. In vivo, we assessed intravesical retention, antitumor efficacy, and histopathological markers (TUNEL, Ki67) in a BCa xenograft BALB/C nude mouse model, alongside systemic safety profiling. The Phl-erda@Ab exhibited sharp pH sensitivity, releasing 49% of the drug payload within 1 h at pH 5.3 while maintaining minimal release at pH 7.4 and 6.5. Liposome retention after intravesical instillation was doubled compared with non-targeted Phl-erda in mice. The Phl-erda@Ab intravesical therapy demonstrated effective antitumor activity, including maximal necrosis, the highest TUNEL-positive apoptotic index, and the lowest Ki67 proliferation index, compared to other groups. No significant pathological damage to major organs was observed. In summary, Phl-erda@Ab enables FGFR3-targeted, pH-triggered intravesical delivery with enhanced intravesical retention, improved antitumor activity, and favorable local safety, providing preclinical evidence to support clinical translation in FGFR3-overexpressing BCa.
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BibTeX
@article{liang2026phresponsive,
title = {{pH-Responsive Erdafitinib Liposomes with FGFR3 Targeting for Intravesical Bladder Cancer Therapy}},
author = {Hongxia Liang and Galong Li and Wenli Zhang and Wei Wang and Dongyan Li and Yuanyuan Cheng and Minghui Song and Xiaopan Xu and Hongbing Lu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209014},
url = {https://www.mdpi.com/1422-0067/27/20/9014},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - pH-Responsive Erdafitinib Liposomes with FGFR3 Targeting for Intravesical Bladder Cancer Therapy
AU - Hongxia Liang
AU - Galong Li
AU - Wenli Zhang
AU - Wei Wang
AU - Dongyan Li
AU - Yuanyuan Cheng
AU - Minghui Song
AU - Xiaopan Xu
AU - Hongbing Lu
PY - 2026
DA - 2026/10/11
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209014
UR - https://www.mdpi.com/1422-0067/27/20/9014
AB - Fibroblast growth factor receptor 3 (FGFR3) is a key oncogenic driver in bladder cancer (BCa). Although erdafitinib, the pioneering FGFR3 inhibitor, is approved for clinic use, its oral administration frequently causes inadequate therapeutic effect and side effects. Here, we report a pH-responsive and erdafitinib-loaded liposomal nanosystem with surface modification of anti-FGFR3 antibodies (Phl-erda@Ab), which demonstrates improved antitumor effects in intravesical instillation therapy. In RT112 cells, we evaluated targeted uptake and antiproliferative activity. In vivo, we assessed intravesical retention, antitumor efficacy, and histopathological markers (TUNEL, Ki67) in a BCa xenograft BALB/C nude mouse model, alongside systemic safety profiling. The Phl-erda@Ab exhibited sharp pH sensitivity, releasing 49% of the drug payload within 1 h at pH 5.3 while maintaining minimal release at pH 7.4 and 6.5. Liposome retention after intravesical instillation was doubled compared with non-targeted Phl-erda in mice. The Phl-erda@Ab intravesical therapy demonstrated effective antitumor activity, including maximal necrosis, the highest TUNEL-positive apoptotic index, and the lowest Ki67 proliferation index, compared to other groups. No significant pathological damage to major organs was observed. In summary, Phl-erda@Ab enables FGFR3-targeted, pH-triggered intravesical delivery with enhanced intravesical retention, improved antitumor activity, and favorable local safety, providing preclinical evidence to support clinical translation in FGFR3-overexpressing BCa.
SN - 1422-0067
ER -