Closing the loop in nanotheranostics: from ¹²⁴I separation to intrinsically radiolabeled platinum nanoparticles for potential PET/CT-guided photothermal therapy

Abstract

Closing the loop in nanotheranostics, we integrate radionuclide production with functional nanomedicine through mesoporous alumina based radiochemical separation of no-carrier-added (NCA) ¹²⁴I and its direct incorporation into protein functionalized platinum nanoparticles. The intrinsically radiolabeled [¹²⁴I]I-Pt@GA shows high labeling efficiency, excellent stability, quantitative PET imaging, and effective photothermal cancer cell ablation.

---

Nanotheranostics has emerged as a compelling approach for precision oncology, bringing diagnosis and therapy together within a single platform, especially when combined with quantitative imaging tools such as positron emission tomography (PET).^1–4 Among the available PET radionuclides, ¹²⁴I is particularly well suited for tracking nanoparticle biodistribution because of its relatively long half-life.^5–9 However, its broader use has been limited by challenges in both radiochemical separation and integration with nanomaterials. Conventionally, ¹²⁴I is recovered from irradiated targets by dry distillation, a method that is technically demanding and requires specialized infrastructure.^10,11 In contrast, mesoporous alumina-based chromatography offers a simpler and more robust alternative for isolating ¹²⁴I under milder conditions, with clear potential for direct nanoparticle labeling.^12,13 Despite these advances, a coherent strategy that directly connects radionuclide separation with functional nanotheranostic design for PET-guided photothermal therapy is still lacking. Conventionally, radionuclide production, radiochemical purification, nanoparticle synthesis, and radiolabeling are performed as separate and sequential operations, often requiring additional processing steps and repeated optimization. Such compartmentalized workflows increase complexity and can impede efficient translation of radionuclides into functional nanotheranostic systems.

Here, we address this gap by bringing together radionuclide production, efficient separation, and functional nanoplatform design within a single framework. ¹²⁴I was produced via the ¹²⁴Te (p,n) ¹²⁴I reaction using a natural TeO₂ target under 14 MeV proton irradiation, followed by its isolation using a mesoporous alumina-based chromatographic method developed in this work.^12,13 By linking radioisotope production, radiochemical separation, nanomaterial fabrication, and multimodal imaging-guided therapy within a single workflow, this study closes the loop between radiochemical processing and nanotheranostic design. The separated ¹²⁴I was then directly incorporated into gum arabic glycoprotein functionalized platinum nanoparticles (Pt@GA NPs) (Fig. 1a). This intrinsic radiolabeling approach affords high labeling efficiency while preserving the physicochemical integrity and photothermal properties of the NPs. The resulting system enables quantitative PET imaging alongside effective photothermal therapy, offering a streamlined route from radioisotope production and separation to image guided treatment.

Fig. 1 (a) Schematic illustration of synthesis of Pt@GA NPs followed by radiolabeling with ¹²⁴I having potential for PET guided PTT. (b) Particle size distribution plot of Pt@GA NPs from DLS. (c) HRTEM image of Pt@GA NPs. The insets of the image display the SAED pattern and a magnified view of the Pt@GA NPs. (d) Particle size distribution plot of Pt@GA NPs from TEM.

Mesoporous alumina, prepared via a solid-state mechanochemical route as reported earlier, was employed as the chromatographic medium for ¹²⁴I separation.^12,13 The irradiated target was dissolved in 0.1 M NaOH, adjusted to near-neutral pH (∼6), and passed through a compact column. Under these conditions, ¹²⁴I was selectively retained, while other species were removed by washing with water, followed by elution using dilute NaOH (0.01 M) (Fig. S1). Gamma spectrometry revealed no detectable extraneous radionuclides (other than that of other iodine radioisotopes produced due to use of the natural TeO₂ target) (Fig. S2), indicating high radionuclidic purity. Complementary ICP-AES analysis of the decayed fraction showed Te levels below 0.01 ppm, further confirming the suitability of the isolated ¹²⁴I for subsequent radiopharmaceutical applications.

Protein functionalized Pt NPs were prepared by reducing chloroplatinic acid in the presence of gum arabic, resulting in a stable aqueous dispersion. The particles showed an average hydrodynamic size of 22.06 ± 0.15 nm with a low polydispersity index (PDI) (Fig. 1b), while TEM images revealed smaller, quasi-spherical Pt cores of 4.8 ± 1.4 nm (Fig. 1c and d). XRD analysis confirmed the formation of crystalline Pt with a face centred cubic structure (Fig. S5), and XPS measurements indicated that platinum is predominantly present in the metallic state,^14,15 along with surface functionalities associated with the gum arabic coating (Fig. S8) (details are given in the SI). The presence of gum arabic helps maintain colloidal stability and improves biocompatibility, making the nanoplatform suitable for subsequent biological and therapeutic studies.

The photothermal performance of Pt@GA NPs was evaluated under 808 nm laser irradiation at different concentrations and power densities. A rapid increase in temperature was observed for the NPs, with concentrations of 0.5 and 1.0 mg mL⁻¹ reaching the therapeutic window (∼42–44 °C) within a few minutes, while lower concentrations showed a more modest response (Fig. 2a). In contrast, deionized water under identical conditions exhibited only a minimal temperature rise, confirming that the heating originates from the NPs (Fig. S10).

Fig. 2 (a) Photothermal curves of Pt@GA NPs at different concentrations under 808 nm laser irradiation at a power of 0.68 W. (b) Photothermal curves of 0.5 mg mL⁻¹ of Pt@GA NPs at different powers of the 808 nm laser. (c) Recycling heating capability of 0.5 mg mL⁻¹ Pt@GA NPs at a power of 0.68 W. (d) IR thermograms of 0.5 mg mL⁻¹ of Pt@GA NP solution showing an increase in temperature under 808 nm laser irradiation at 0.68 W power.

The temperature increase depended on both the concentration of NPs and laser power, with higher power leading to faster heating (Fig. 2b). Importantly, the Pt@GA NPs maintained consistent heating behaviour over multiple irradiation cycles, indicating good photothermal stability (Fig. 2c). The heating capability of 0.5 mg mL⁻¹ Pt@GA NPs was also confirmed by the colour change observed in the IR thermograms (Fig. 2d). Together, these results show that the Pt@GA NP system can efficiently convert near-infrared light into heat in a controlled and reproducible manner.

The biological response of Pt@GA NPs was evaluated in A549 cells to assess both cell viability and photothermal therapeutic effect. The NPs alone showed minimal cytotoxicity, with cell viability remaining above 90% even at higher concentrations after 48 h incubation, indicating good biocompatibility (Fig. S12a). In contrast, upon exposure to 808 nm laser irradiation, a marked decrease in cell viability was observed, demonstrating a clear photothermal effect (Fig. S12b). This response was concentration dependent, with higher concentrations of NPs leading to greater cell death under irradiation. Microscopy images further supported these findings, showing noticeable changes in cell morphology and reduced cell density only in the groups treated with both Pt@GA NPs and laser irradiation (Fig. S12c). Cells treated with NPs alone or laser irradiation alone largely retained their normal morphology. Together, these results confirm that Pt@GA NPs are well tolerated under dark conditions but become effective therapeutic agents upon near-infrared irradiation. While the present biological evaluations establish the efficacy of the Pt@GA NPs as photothermal agents, more detailed mechanistic studies on the various cell death pathways will be undertaken in future work to elucidate the specific cellular pathways involved in treatment-induced cell death.

With a stable and functionally active nanoplatform in hand, we next examined radiolabeling with ¹²⁴I. The strong affinity of iodide for noble metal surfaces enabled direct labeling of Pt@GA NPs without additional chelators.^16,17 Iodide formed stable Pt–I bonds through chemisorption on the platinum surface by simple incubation of the NPs with the separated ¹²⁴I, with radiochemical yields consistently above 99% as confirmed by size exclusion chromatography (Fig. S13). Consistent with this, the resulting [¹²⁴I]I-Pt@GA NPs showed good stability in both phosphate buffered saline and human serum, retaining more than 94% of the activity over 7 days, suggesting a strong association of ¹²⁴I with the surface of NPs (Fig. S14).

In vitro PET imaging provided a clear and quantifiable signal from the radiolabeled NPs across different activity levels (Fig. 3a). In parallel, CT imaging showed a concentration dependent increase in contrast, consistent with the high X-ray attenuation of Pt (Fig. 3b and c). These observations collectively imply that [¹²⁴I]I-Pt@GA NPs offer a dual PET/CT imaging platform, without compromising their photothermal therapeutic potential.

Fig. 3 (a) In vitro PET images of [¹²⁴I]I-Pt@GA NPs at different activity levels of ¹²⁴I. (b) CT images of Pt@GA NPs at varying concentrations, where water was used as the control. (c) Plot of mass concentration versus Hounsfield units (HU) demonstrating a linear relationship, indicating concentration dependent X-ray attenuation.

The combined outcomes of this research demonstrate a cohesive strategy that bridges radionuclide production and separation processes with the engineering and application of functional nanomaterials. The use of mesoporous alumina enables a straightforward and mild approach for obtaining high-purity ¹²⁴I, which can be directly integrated with Pt@GA NPs without additional modification. At the same time, the NPs retain their photothermal properties and show good biocompatibility, while also supporting stable radiolabeling for quantitative PET imaging. The additional CT contrast further extends the system toward multimodal imaging.

Rather than treating these steps independently, this work brings them into a single workflow, offering a practical path from radioisotope production to image-guided photothermal therapy. More broadly, this approach highlights how radiochemical processing can be considered as part of nanomaterial design and may be extended to other radionuclides and nanoplatforms.

Author contributions

Sanchita Ghosh: writing – original draft, validation, formal analysis, data curation, and investigation. Rajwardhan N. Ambade: data curation. Ramu Ram: data curation. Kanhu C Barick: data curation and formal analysis. Apurav Guleria: data curation and formal analysis. Suresh Chand Sharma: data curation. Minati Nayak: data curation. Amit Kunwar: data curation and formal analysis. Kaustava Bhattacharya: data curation and formal analysis. Rubel Chakravarty: writing – review & editing, supervision, project administration, and conceptualization.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information is available. See DOI: https://doi.org/10.1039/d6na00347h.

Acknowledgements

The authors acknowledge that research at the Bhabha Atomic Research Centre (BARC) is part of the ongoing activities of the Department of Atomic Energy (DAE), Government of India, and is fully supported through internal funding. The authors sincerely thank Dr Y. K. Bhardwaj (Associate Director, Radiochemistry and Isotope Group, BARC), Dr T. Das (Head, Radiopharmaceuticals Division, BARC), Mr N. S. Baghel (Head, Radiation Medicine Centre (G), BARC), Dr N. Choudhury (Head, Chemistry Division, BARC), Dr V. Sudarsan (Head, Radiation and Photochemistry Division, BARC) and Dr S. Chakraborty (Head, Radiochemicals Section, Radiopharmaceuticals Division, BARC) for their constant encouragement and support. The authors also thank the staff members of the BARC–TIFR Pelletron facility for their assistance in the irradiation of the target. The authors acknowledge the Sophisticated Analytical Instrument Facility (SAIF), Indian Institute of Technology Bombay, for providing TEM imaging support.

References

1. W. Hu, X. Wang, Y. Feng, Y. Wang, H. Wang, L. Feng, B. Yang, Y. Gao, D. Jiang and M. Li, ACS Appl. Mater. Interfaces, 2025, 17, 56704–56718.
2. J. Sun, L. Li, W. Cai, A. Chen and R. Zhang, ACS Appl. Bio Mater., 2021, 4, 5312–5323.
3. N. Priyadarshni, R. Singh and M. K. Mishra, Cancer Lett., 2024, 587, 216710.
4. M. A. B. Saddique, M. D. Amjad, H. Tahir and K. Sajid, in Nanotheranostics and Precision Oncology, Elsevier, 2026, pp. 431–462.
5. V. V. Belov, A. A. Bonab, A. J. Fischman, M. Heartlein, P. Calias and M. I. Papisov, Mol. Pharmaceutics, 2011, 8, 736–747.
6. J. Y. Lee and J. H. Park, New J. Chem., 2025, 49, 19472–19478.
7. T. Krönke, K. Kopka and C. Mamat, RSC Med. Chem., 2025, 16, 1856–1864.
8. D. Kersting, W. Jentzen, P. Fragoso Costa, M. Sraieb, P. Sandach, L. Umutlu, M. Conti, F. Zarrad, C. Rischpler, W. P. Fendler, K. Herrmann and M. Weber, Sci. Rep., 2021, 11, 17477.
9. S. Takyu, H. Ikeda, H. Wakizaka, F. Nishikido, K.-i. Matsumoto, H. Tashima, H. Suzuki, Y. Funaki, H. Watabe and M. Takahashi, Appl. Phys. Express, 2023, 16, 116001.
10. P. Bzowski, D. Borys, K. Gorczewski, A. Chmura, K. Daszewska, I. Gorczewska, A. Kastelik-Hryniewiecka, M. Szydło, A. d'Amico and M. Sokół, EJNMMI Phys., 2022, 9, 41.
11. K. Kumar and A. Ghosh, Molecules, 2021, 26, 414.
12. R. Chakravarty, J. Bahadur, S. Lohar, S. Jadhav, D. Sen and S. Chakraborty, SN Appl. Sci., 2021, 3, 77.
13. R. Chakravarty, J. Bahadur, S. Lohar, H. D. Sarma, D. Sen, R. Mishra, S. Chakraborty and A. Dash, Microporous Mesoporous Mater., 2019, 287, 271–279.
14. C. He, S. Sankarasubramanian, A. Ells, J. Parrondo, C. Gumeci, M. Kodali, I. Matanovic, A. K. Yadav, K. Bhattacharyya and N. Dale, ACS Catal., 2021, 11, 7006–7017.
15. D. Tyagi, K. Scholz, S. Varma, K. Bhattacharya, S. Mali, P. Patil and S. Bharadwaj, Int. J. Hydrogen Energy, 2012, 37, 3602–3611.
16. S. Ghosh, D. Banerjee, A. Guleria and R. Chakravarty, Nucl. Med. Biol., 2024, 138, 108947.
17. M. P. Soriaga, Chem. Rev., 1990, 90, 771–793.

---