Technetium-99m Radiolabeled Carboplatin Polymeric Nanoparticlesfor Imaging and Treatment of Epithelial Ovarian Cancer
Introduction: Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy due to its typically late diagnosis and high recurrence rates. Conventional carboplatin-based therapies are limited by systemic toxicity and chemoresistance. To overcome these barriers, we developed a theranostic system based on Pluronic F-127 nanomicelles encapsulating carboplatin and radiolabeled with technetium-99m (99ᵐTc), aiming for targeted delivery, sustained drug release, and concurrent imaging capability. Materials and Methods: Carboplatin-loaded Pluronic nanomicelles were prepared by direct dissolution and characterized via dynamic light scattering (DLS), scanning and cryo-electron microscopy (SEM, Cryo-SEM), and energy-dispersive X-ray spectroscopy (EDS). Drug release was assessed by UV-Vis spectrophotometry. In vitro cytotoxicity was evaluated on SK-OV-3 cells using MTT assays. Nanomicelles were radiolabeled with 99ᵐTc, and radiochemical purity/stability were confirmed by TLC. in vivo pharmacokinetics, biodistribution, and biochemical safety profiles were studied in Wistar and Balb/c mice using gamma counting and serum assays. Results: Nanomicelles exhibited a mean diameter of 274.4 nm with low PDI (0.051), spherical morphology, and high encapsulation efficiency. EDS confirmed homogeneous platinum distribution. The release profile showed a biphasic kinetic with ≈96% cumulative release in 25 h. Cytotoxicity assays revealed time- and dose-dependent effects, with the nanoformulation showing superior or comparable efficacy to free carboplatin. Radiolabeling efficiency exceeded 90% and remained stable for 24 h. Pharmacokinetic modeling indicated a prolonged half-life (12.73 h), extensive volume of distribution, and slow systemic clearance. Biodistribution favored renal elimination with minimal off-target accumulation. Biochemical analyses indicated no significant hepatotoxicity or nephrotoxicity, though elevated lipase suggested potential pancreatic involvement. Discussion: The PLU-carboplatin nanomicelles demonstrated physicochemical robustness, sustained-release kinetics, and effective in vitro cytotoxicity. Radiolabeling with 99ᵐTc enabled simultaneous biodistribution tracking, affirming their theranostic potential. Pharmacokinetic and safety profiles support the feasibility of this nanoformulation as a targeted therapeutic and diagnostic platform for EOC, warranting further translational development. Conclusion: Technetium-99m radiolabeled Pluronic F-127 nanomicelles encapsulating carboplatin exhibit desirable theranostic characteristics, including structural integrity, controlled drug release, dual cytotoxic and imaging capacity, and minimal systemic toxicity. These findings position the system as a promising candidate for targeted therapy and real-time monitoring in epithelial ovarian cancer and justify its advancement to more complex preclinical models.
Authors
- Derya İlem‐Özdemir (ORCID: https://orcid.org/0000-0002-1062-498X)
- Luciana Magalhães Rebêlo Alencar (ORCID: https://orcid.org/0000-0001-8210-2016)
- Claudiana de Jesus Felismino
- Pierre Basílio Almeida Fechine (ORCID: https://orcid.org/0000-0002-7822-2354)
- Marília Amável Gomes Soares (ORCID: https://orcid.org/0000-0003-2390-8428)
- Pedro Filho Noronha Souza (ORCID: https://orcid.org/0000-0003-2524-4434)
- Natália Cristina Gomes-da-Silva (ORCID: https://orcid.org/0000-0002-9088-6671)
- Eduardo Ricci-Junior
- Natália Mayumi Andrade Yoshiara
- Ralph Santos-Oliveira
Institutions
- Universidade Federal do Rio de Janeiro (BR)
- Universidade Federal do Ceará (BR)
- Ege University (TR)
- Nuclear Engineering Institute (BR)
- Universidade Federal do Maranhão (BR)
Publication Details
- Journal
- Current Medicinal Chemistry
- Published
- 2026-06-17
- DOI
- https://doi.org/10.2174/0109298673430469260212173838
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.00