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Imaging and Downstaging Bladder Cancer with the 177Lu-Labeled Bioorthogonal Nanoprobe
Yueping Li1, Shanshan Shan1, Ruru Zhang1
1State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, P. R. China.
Abstract:
Efforts on bladder cancer treatment have been shifting from extensive surgery to organ preservation in the past decade. To this end, we herein develop a multifunctional nanoagent for bladder cancer downstaging and bladder-preserving therapy by integrating mucosa penetration, reduced off-target effects, and internal irradiation therapy into a nanodrug. Specifically, an iron oxide nanoparticle was used as a carrier that was coated with hyaluronic acid (HA) for facilitating mucosa penetration. Dibenzocyclooctyne (DBCO) was introduced into the HA coating layer to react through bioorthogonal reaction with azide as an artificial receptor of bladder cancer cells, to improve the cellular internalization of the nanoprobe labeled with 177Lu. Through magnetic resonance imaging, the targeted imaging of both nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) was realized after intravesical instillation of the multifunctional probe, both NMIBC and MIBC were found downstaged, and the metastasis was inhibited, which demonstrates the potential of the multifunctional nanoprobe for bladder preservation in bladder cancer treatment.
Insights
A new nanoagent aids bladder cancer treatment by enabling organ preservation. This nanodrug targets and images tumors, downstages cancer, and inhibits metastasis, offering a bladder-preserving therapy option.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanomedicine
Background:
- Bladder cancer treatment is evolving towards organ preservation over extensive surgery.
- Developing targeted therapies that minimize side effects is crucial for bladder preservation.
Purpose of the Study:
- To develop a multifunctional nanoagent for bladder cancer downstaging and bladder-preserving therapy.
- To integrate mucosa penetration, reduced off-target effects, and internal irradiation into a single nanodrug.
Main Methods:
- An iron oxide nanoparticle coated with hyaluronic acid (HA) was used as a carrier.
- Dibenzocyclooctyne (DBCO) was introduced for bioorthogonal reaction with azide receptors on cancer cells.
- The nanoprobe was labeled with 177Lu for internal irradiation and imaged using magnetic resonance imaging (MRI).
Main Results:
- The nanoagent demonstrated effective mucosa penetration and targeted imaging of nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) via intravesical instillation.
- Both NMIBC and MIBC were successfully downstaged.
- Inhibition of metastasis was observed, indicating reduced off-target effects.
Conclusions:
- The multifunctional nanoprobe shows significant potential for bladder preservation in bladder cancer treatment.
- The integrated approach of targeted imaging, downstaging, and internal irradiation offers a promising bladder-preserving therapeutic strategy.
