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.

Background: Nanomedicine approaches for cancer therapy face significant challenges, including a poor tumor accumulation, limited therapeutic efficacy, and systemic toxicity. We hypothesized that controlling the clustering of poly(acrylic acid-co-maleic acid) (PAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) would enhance their magnetic properties for improved targeting, while enabling a pH-responsive drug release in tumor microenvironments. Methods: PAM-stabilized SPION clusters were synthesized via arrested precipitation, characterized for physicochemical and magnetic properties, and evaluated for doxorubicin loading and pH-dependent release. A dual targeting approach combining antibody conjugation with magnetic guidance was assessed in cellular models, including a novel alternating magnetic field (AMF) pre-treatment protocol. Results: PAM-SPION clusters demonstrated controlled size distributions (60–100 nm), excellent colloidal stability, and enhanced magnetic properties, particularly for larger crystallites (13 nm). The formulations exhibited a pH-responsive drug release (8.5% at pH 7.4 vs. 14.3% at pH 6.5) and a significant enhancement of AMF-triggered release (17.5%). The dual targeting approach achieved an 8-fold increased cellular uptake compared to non-targeted formulations. Most notably, the novel AMF pre-treatment protocol demonstrated an 87% improved therapeutic efficacy compared to conventional post-treatment applications. Conclusions: The integration of targeting antibodies, magnetic guidance, and a pH-responsive PAM coating creates a versatile theranostic platform with significantly enhanced drug delivery capabilities. The unexpected synergistic effect of the AMF pre-treatment represents a promising new approach for improving the therapeutic efficacy of nanoparticle-based cancer treatments.

Graphene-based materials (GBMs) have shown significant promise in cancer therapy due to their unique physicochemical properties, biocompatibility, and ease of functionalization. Their ability to target solid tumors, penetrate the tumor microenvironment (TME), and act as efficient drug delivery platforms highlights their potential in nanomedicine. However, the complex and dynamic nature of the TME, characterized by metabolic heterogeneity, immune suppression, and drug resistance, poses significant challenges to effective cancer treatment. GBMs offer innovative solutions by enhancing tumor targeting, facilitating deep tissue penetration, and modulating metabolic pathways that contribute to tumor progression and immune evasion. Their functionalization with targeting ligands and biocompatible polymers improves their biosafety and specificity, while their ability to modulate immune cell interactions within the TME presents new opportunities for immunotherapy. Given the role of metabolic reprogramming in tumor survival and resistance, GBMs could be further exploited in metabolism-targeted therapies by disrupting glycolysis, mitochondrial respiration, and lipid metabolism to counteract the immunosuppressive effects of the TME. This review focuses on discussing research studies that design GBM nanocomposites with enhanced biodegradability, minimized toxicity, and improved efficacy in delivering therapeutic agents with the intention to reprogram the TME for effective anticancer therapy. Additionally, exploring the potential of GBM nanocomposites in combination with immunotherapies and metabolism-targeted treatments could lead to more effective and personalized cancer therapies. By addressing these challenges, GBMs could play a pivotal role in overcoming current limitations in cancer treatment and advancing precision oncology.