Targeted Inhibition of Lymphovascular Invasion Formation with CREKA Peptide-Modified Silicasomes to Boost Chemotherapy in Bladder Cancer

Despite its significant clinical efficacy as a first-line treatment for advanced bladder cancer, cisplatin-based chemotherapy provides a limited benefit for patients with lymphovascular invasion (LVI), which is characterized by the presence of tumor emboli within blood vessels and associated with en...

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Bibliographic Details
Published in:Nano letters 2024-08, Vol.24 (33), p.10186-10195
Main Authors: Wu, Zhouliang, Li, Bozhao, Qie, Yunkai, Wu, Suying, Qi, Feilong, Chu, Tianjiao, Nie, Guangjun, Hu, Hailong
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cell Line, Tumor
Cisplatin - chemistry
Cisplatin - pharmacology
Cisplatin - therapeutic use
Humans
Mice
Nanoparticles - chemistry
Neoplasm Invasiveness - prevention & control
Oligopeptides
Peptides, Cyclic - chemistry
Peptides, Cyclic - pharmacology
Peptides, Cyclic - therapeutic use
Silicon Dioxide - chemistry
Tumor Microenvironment - drug effects
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - pathology
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Summary:Despite its significant clinical efficacy as a first-line treatment for advanced bladder cancer, cisplatin-based chemotherapy provides a limited benefit for patients with lymphovascular invasion (LVI), which is characterized by the presence of tumor emboli within blood vessels and associated with enhanced cisplatin resistance and metastatic potential. Notably, platelets, a critical component of LVI, hinder the delivery of chemotherapeutic agents to tumors and facilitate metastasis. Consequently, platelet function inhibition holds the potential to disrupt LVI formation, as well as augment the antitumor activity of cisplatin. Herein, we developed a tumor microenvironment-targeted nanodrug with lipid-coated mesoporous silica nanoparticles (silicasomes) that synergistically combines cisplatin with an antiplatelet agent, tirofiban, for bladder cancer treatment. The customized nanodrug can concurrently prevent LVI formation and enhance the chemotherapeutic efficacy without significant adverse effects. This study supports the integration of chemotherapy and antiplatelet therapy via a silicasome-based nanosystem as a highly promising strategy for bladder cancer management.
ISSN:1530-6984
1530-6992
1530-6992
DOI:10.1021/acs.nanolett.4c02485