Actinium-225 (²²⁵Ac) is receiving increased attention for its application in targeted radionuclide therapy, due to the short range of its emitted alpha particles in conjunction with their high linear energy transfer, which lead to the eradication of tumor cells while sparing neighboring healthy tissue. The objective of our study was the evaluation of a gold nanoparticle radiolabeled with ²²⁵Ac as an injectable radiopharmaceutical form of brachytherapy for local radiation treatment of cancer. Au@TADOTAGA was radiolabeled with ²²⁵Ac at pH 5.6 (30 min at 70 °C), and in vitro stability was evaluated. In vitro cytotoxicity was assessed in U-87 MG cancer cells, and in vivo biodistribution was performed by intravenous and intratumoral administration of [²²⁵Ac]²²⁵Ac-Au@TADOTAGA in U-87 MG tumor-bearing mice. A preliminary study to assess therapeutic efficacy of the intratumorally-injected radio-nanomedicine was performed over a period of 22 days, while the necrotic effect on tumors was evaluated by a histopathology study. We have shown that [²²⁵Ac]²²⁵Ac-Au@TADOTAGA resulted in the retardation of tumor growth after its intratumoral injection in U87MG tumor-bearing mice, even though very low activities were injected per mouse. This gold nanoparticle radiopharmaceutical could be applied as an unconventional brachytherapy in injectable form for local radiation treatment of cancer.

Theranostic radioisotope pairs such as Gallium-68 (⁶⁸Ga) for Positron Emission Tomography (PET) and Lutetium-177 (¹⁷⁷Lu) for radioisotopic therapy, in conjunction with nanoparticles (NPs), are an emerging field in the treatment of cancer. The present work aims to demonstrate the ability of condensed colloidal nanocrystal clusters (co-CNCs) comprised of iron oxide nanoparticles, coated with alginic acid (MA) and stabilized by a layer of polyethylene glycol (MAPEG) to be directly radiolabeled with ⁶⁸Ga and its therapeutic analog ¹⁷⁷Lu. ⁶⁸Ga/¹⁷⁷Lu- MA and MAPEG were investigated for their in vitro stability. The biocompatibility of the non-radiolabeled nanoparticles, as well as the cytotoxicity of MA, MAPEG, and [¹⁷⁷Lu]Lu-MAPEG were assessed on 4T1 cells. Finally, the ex vivo biodistribution of the ⁶⁸Ga-labeled NPs as well as [¹⁷⁷Lu]Lu-MAPEG was investigated in normal mice. Radiolabeling with both radioisotopes took place via a simple and direct labelling method without further purification. Hemocompatibility was verified for both NPs, while MTT studies demonstrated the non-cytotoxic profile of the nanocarriers and the dose-dependent toxicity for [¹⁷⁷Lu]Lu-MAPEG. The radiolabeled nanoparticles mainly accumulated in RES organs. Based on our preliminary results, we conclude that MAPEG could be further investigated as a theranostic agent for PET diagnosis and therapy of cancer.

The use of conventional methods for the treatment of cancer, such as chemotherapy or radiotherapy, and approaches such as brachytherapy in conjunction with the unique properties of nanoparticles could enable the development of novel theranostic agents. The aim of our current study was to evaluate the potential of iron oxide nanoparticles, coated with alginic acid and polyethylene glycol, functionalized with the chemotherapeutic agent doxorubicin and the monoclonal antibody bevacizumab, to serve as a nanoradiopharmaceutical agent against breast cancer. Direct radiolabeling with the therapeutic isotope Lutetium-177 (¹⁷⁷Lu) resulted in an additional therapeutic effect. Functionalization was accomplished at high percentages and radiolabeling was robust. The high cytotoxic effect of our radiolabeled and non-radiolabeled nanostructures was proven in vitro against five different breast cancer cell lines. The ex vivo biodistribution in tumor-bearing mice was investigated with three different ways of administration. The intratumoral administration of our functionalized radionanoconjugates showed high tumor accumulation and retention at the tumor site. Finally, our therapeutic efficacy study performed over a 50-day period against an aggressive triple-negative breast cancer cell line (4T1) demonstrated enhanced tumor growth retention, thus identifying the developed nanoparticles as a promising nanobrachytherapy agent against breast cancer.

The aim of this study was to develop a bioimaging probe based on magnetic iron oxide nanoparticles (MIONs) surface functionalized with the copolymer (p(MAA-g-EGMA)), which were radiolabeled with the positron emitter Gallium-68. The synthesis of the hybrid MIONs was realized by hydrolytic condensation of a single ferrous precursor in the presence of the copolymer. The synthesized MagP MIONs displayed an average D_h of 87 nm, suitable for passive targeting of cancerous tissues through the enhanced permeation and retention (EPR) effect after intravenous administration, while their particularly high magnetic content ascribes strong magnetic properties to the colloids. Two different approaches were explored to develop MIONs radiolabeled with ⁶⁸Ga: the chelator-mediated approach, where the chelating agent NODAGA-NHS was conjugated onto the MIONs (MagP-NODAGA) to form a chelate complex with ⁶⁸Ga, and the chelator-free approach, where ⁶⁸Ga was directly incorporated onto the MIONs (MagP). Both groups of NPs showed highly efficient radiolabeling with ⁶⁸Ga, forming constructs which were stable with time, and in the presence of PBS and human serum. Ex vivo biodistribution studies of [⁶⁸Ga]Ga- MIONs showed high accumulation in the mononuclear phagocyte system (MPS) organs and satisfactory blood retention with time. In vivo PET imaging with [⁶⁸Ga]Ga-MagP MIONs was in accordance with the ex vivo biodistribution results. Finally, the MIONs showed low toxicity against 4T1 breast cancer cells. These detailed studies established that [⁶⁸Ga]Ga- MIONs exhibit potential for application as tracers for early cancer detection.

Due to their intriguing emission profile, Terbium-161 (¹⁶¹Tb) radiopharmaceuticals seem to bring significant advancement in theranostic applications to cancer treatment. The combination of ¹⁶¹Tb with nanoscale brachytherapy as an approach for cancer treatment is particularly advantageous and promising. Herein, we propose the application of a hybrid nanosystem comprising gold decorated (Au@TADOTAGA) iron oxide nanoflowers as a form of injectable nanobrachytherapy for the local treatment of breast cancer. More specifically, Au@TADOTAGA and NFAu@TADOTAGA NPs were efficiently radiolabeled with ¹⁶¹Tb, and their in vitro stability was assessed up to 21 d post-radiolabeling. Furthermore, their cytotoxic profile against 4T1 breast cancer cells was evaluated, and their ex vivo biodistribution characteristics were revealed after intratumoral injection in the same animal model. The enhanced retention at the tumor site urged us to evaluate the therapeutic effect of the [¹⁶¹Tb]Tb-NFAu@TADOTAGA nanosystem after intratumoral administration to 4T1-tumor-bearing mice, over a period of 24 days. Three different therapeutic protocols were performed in order to identify which therapeutic approach would offer the optimum results and identify the proposed nanosystem as a promising nanoscale brachytherapy agent.

Gold nanoparticles (AuNPs) have been extensively studied in cancer treatment research since they have special physicochemical characteristics such as facile surface functionalization with various chemical groups, low toxicity, favorable biocompatibility, and the ability to passively accumulate in tumors through the enhanced permeability and retention (EPR) effect. Prostate cancer cells exhibit an overexpression of the Prostate-Specific Membrane Antigen (PSMA), which therefore represents an ideal candidate for the development of nanoplatforms targeting PSMA overexpressed on these cells. Lutetium-177 (¹⁷⁷Lu) is a β-particle emitter with a half-life of 6.7 days. This radionuclide is very promising for the development of theranostic platforms as it emits β⁻ particles, which are suitable for therapy, and γ-photons, capable of SPECT imaging. The combination of ¹⁷⁷Lu with AuNPs functionalized with PSMA for targeted delivery offers a promising tool for both diagnosis and therapy of prostate cancer. In this study, we focused on the synthesis and in vitro evaluation of PSMA-targeted AuNPs radiolabeled with ¹⁷⁷Lu. The AuNPs were functionalized with the TADOTAGA chelator, which enables effective radiolabeling with the radiometal, as well as with a PSMA molecule, which comprises the PSMA targeting moiety (vehicle) of the nanoconstruct. Radiolabeling of the functionalized AuNPs with ¹⁷⁷Lu was fast and robust. Subsequent studies focused on the in vitro stability and cellular interaction with two prostate cancer cell lines with different PSMA expression levels, in both 2D and 3D cell cultures, to assess effective targeting. Results indicate that radiolabeled AuNPs exhibit selective interaction with PSMA-expressing cells and present a stronger in vitro cytotoxic effect when functionalized with the PSMA molecule, confirming their potential as theranostic agents and warranting further investigation in LNCaP tumor-bearing mice.