A Novel Approach for Pancreatic Cancer Therapy: Cell-Membrane–Coated Radioactive Gold Nanoparticles
Abstract
Purpose
To establish, for the first time, a biomimetic nanobrachytherapy platform using radioactive gold nanoparticles coated with PANC-1 cell membrane m198AuNP. This study evaluates their physicochemical properties, nanoscale dose deposition, and feasibility for selective in vitro application as a targeted treatment for pancreatic cancer.
Methods
198AuNP was produced by neutron irradiation of metallic gold in the IEA-R1 reactor, followed by chemical dissolution to form the radioactive precursor for nanoparticle synthesis via the Turkevich method. PANC-1 membranes were extracted via differential ultracentrifugation and validated by BCA protein quantification. Cell membranes were coated onto both 198AuNPand non-radioactive AuNP (controls) using mechanical extrusion through 100 and 200 nm polycarbonate membranes. Physicochemical characterization was performed by DLS, zeta potential analysis, and TEM. Monte Carlo simulations were employed to model nanoscale dose deposition within concentric shells (from 1 nm to 1 μm) surrounding the source. Cytotoxicity of non-radioactive AuNP and mAuNP was assessed in PANC-1 cells using MTS assays (490 nm absorbance).
Results
Experimental synthesis yielded stable 198AuNP with an average diameter of 35.4 ± 0.4 nm. Following membrane coating, the particle size increased to 48.3 ± 0.9 nm, accompanied by a shift in zeta potential from −32.4 mV to −21.5 mV, confirming successful encapsulation of the radioactive core with a PANC-1 membrane. MC simulations showed the highest absorbed dose localized within the 1 nm membrane region, ensuring high-energy deposition at the target site while minimizing distal damage. MTS assays demonstrated no significant cytotoxicity associated with non-radioactive AuNP, with or without cell membrane coating, confirming the biocompatibility of the platform components.
Conclusion
This work demonstrates the first production of cell-membrane–coated radioactive nanoparticles. The findings highlight the potential of m198AuNP as a novel nanobrachytherapy strategy for pancreatic cancer, supporting future evaluation of targeting specificity, post-decay membrane integrity, therapeutic effectiveness and feasibility toward future in vivo evaluation.