Targeted Accumulation of Reactive Acrolein via Nanoparticle-embedded Reverse Temperature Hydrogel for Bladder Cancer...

Area of Science:

• Biochemistry
• Oncology
• Biomaterials

Background:

• Bladder cancer (BC) recurrence after surgery leads to poor outcomes.
• Intravesical drug instillation for BC is limited by poor retention and obstruction.
• Acetylpolyamine oxidase (PAOX) is suppressed in BC, causing polyamine accumulation.

Purpose of the Study:

• To develop a novel intravesical instillation system for bladder cancer treatment.
• To target the metabolic vulnerability of PAOX deficiency in BC.
• To enhance therapeutic efficacy by prolonging drug retention and inducing cancer cell death.

Main Methods:

• Engineered PAOX/targeting peptide-conjugated nanoparticles.
• Developed a reverse temperature hydrogel for in situ gelation and prolonged retention.
• Utilized multi-platform analysis of patient samples and GEO database to confirm PAOX suppression in BC.

Main Results:

• The nanoparticle-hydrogel system synergistically boosted reactive acrolein synthesis, inducing lethal carbonyl stress.
• Treatment disrupted redox homeostasis, causing mitochondrial dysfunction, lipid peroxidation, and DNA damage.
• Acrolein binding to GAPDH promoted P53 upregulation, facilitating apoptosis in BC cells.

Conclusions:

• This strategy targets tumor-specific metabolic vulnerabilities by enhancing acrolein accumulation.
• The system induces multifaceted cell death, offering a promising new approach for BC treatment.
• The combination of nanoparticles and hydrogels enhances drug retention and therapeutic efficacy.