Exploring the role of RPS2 in muscle-invasive bladder cancer progression and resistance: A nanovesicle-based therapeutic approach

Jiarun Zhang; Hongxu Zhou; Jia Li; Tao Liu; Xiaolong Hou; Xiaoxiao Xu; Yue Zhao; Hao Zhang; Yuanjun Jiang

doi:10.1016/j.jpha.2026.101628

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Article Navigation > Journal of Pharmaceutical Analysis > 2026 > Accepted Manu

Jiarun Zhang, Hongxu Zhou, Jia Li, Tao Liu, Xiaolong Hou, Xiaoxiao Xu, Yue Zhao, Hao Zhang, Yuanjun Jiang. Exploring the role of RPS2 in muscle-invasive bladder cancer progression and resistance: A nanovesicle-based therapeutic approach[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101628

Citation:

Jiarun Zhang, Hongxu Zhou, Jia Li, Tao Liu, Xiaolong Hou, Xiaoxiao Xu, Yue Zhao, Hao Zhang, Yuanjun Jiang. Exploring the role of RPS2 in muscle-invasive bladder cancer progression and resistance: A nanovesicle-based therapeutic approach[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101628

Citation:

Jiarun Zhang, Hongxu Zhou, Jia Li, Tao Liu, Xiaolong Hou, Xiaoxiao Xu, Yue Zhao, Hao Zhang, Yuanjun Jiang. Exploring the role of RPS2 in muscle-invasive bladder cancer progression and resistance: A nanovesicle-based therapeutic approach[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101628

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Exploring the role of RPS2 in muscle-invasive bladder cancer progression and resistance: A nanovesicle-based therapeutic approach

doi: 10.1016/j.jpha.2026.101628

Jiarun Zhang^a,
Hongxu Zhou^b,
Jia Li^c,
Tao Liu^a,
Xiaolong Hou^a,
Xiaoxiao Xu^a,
Yue Zhao^{d
,
,},
Hao Zhang^{a
,
,},
Yuanjun Jiang^{a
,
,}

a. Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, China;
b. Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, 110001, China;
c. Department of Health Management, The First Hospital of China Medical University, Shenyang, 110001, China;
d. Department of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang, 110122, China

Funds:

This study was supported by the National Natural Science Foundation of China (Grant Nos.: 82473067 and 82002669) and Liaoning Plan Project of Science and Technology, China (Grant Nos.: 2025-BSLH-416, 2022-MS-190, and 2023JH2/20200136).

Received Date: May 17, 2025
Accepted Date: Apr. 01, 2026
Rev Recd Date: Mar. 30, 2026
Available Online: Apr. 03, 2026

Abstract

Abstract

Chemotherapy resistance in muscle-invasive bladder cancer (MIBC) remains a major clinical challenge, and the role of ribosomal protein S2 (RPS2) has not been fully clarified. This study investigated the mechanistic association between RPS2 and MIBC progression and developed an asparagine-glycine-arginine (NGR)-modified nanovesicle system for targeted RPS2 modulation to reverse chemotherapy resistance. Single-cell RNA sequencing (scRNA-seq) identified distinct tumor subpopulations, and weighted gene co-expression network analysis (WGCNA) revealed gene modules associated with stemness. Differential expression analysis of patients treated with cisplatin highlighted key genes linked to stemness and resistance. In vitro experiments showed that RPS2 inhibition suppressed proliferation and invasion while enhancing cisplatin sensitivity in MIBC cells. The engineered NGR-modified red blood cell (RBC) membrane vesicles (RMVs) encapsulating RPS2 small interfering RNA (siRNA) (NGR-RMVs@si-RPS2) vesicles effectively targeted tumor vasculature, inhibited xenograft growth, and restored cisplatin sensitivity in resistant tumors, demonstrating strong therapeutic potential. These findings establish RPS2 as a critical regulator of MIBC chemoresistance and present NGR-modified nanovesicles as a promising strategy for improving treatment outcomes.
- Muscle-invasive bladder cancer,
- Ribosomal protein S2,
- Tumor vasculature-targeting peptide NGR,
- Chemotherapy resistance,
- Nanovesicle,
- Ribosomal synthesis

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References(42)

References

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