This study demonstrates a new candidate for targeted magnetic resonance imaging (MRI) contrast agent (CA) based on holmium nanoparticles. MRI is one of the most powerful diagnostic tools in cancer diagnosis which enables anatomical images of soft tissues with a resolution much higher than other imaging techniques. Holmium has been known for its high magnetic moment which can improve MRI signals as T2-MRI CA. This research focuses on modifying folic acid (FA) on the surface of polyethyelene glycol coated- holmium nanoparticles to deliver holmium nanoparticles selectively to the cancer-overexpressed FA receptors, such as cervical cancer. Their preparation and characterization with several analytical instruments such as transmission electron microscopy to observe their shape and size, thermal gravimetric analysis, ultraviolet and infrared spectroscopies to investigate the FA and polyethylene glycol molecules on nanoparticles are also included. From the results, morphology images show a narrow size distribution below 20 nm after the functionalization of polyethyelene glycol-coated holmium nanoparticles with and without FA modification. Based on ultraviolet and infrared spectrum analysis, the presences of FA and polyethylene glycol molecules on nanoparticles were also identified. The typical peaks of FA at around 280 and 360 nm were found on FA-modified nanoparticles spectras. In addition, infrared spectroscopy results at around 2800 cm^–1 originated from polyethylene glycol molecules on nanoparticles was also observed. Furthermore, based on a preliminary cytotoxicity study, there are no significant differences between polyethylene glycol-coated nanoparticles modified with and without FA in terms of toxicity. Based on these results, FA-modified holmium nanoparticles showed promising preliminary results to be utilized as targeted MRI CA for diagnostic purposes.

Gadolinium (Gd) nanoparticles (NPs) are increasingly considered as a viable alternative to clinically employed Gd chelates in magnetic resonance imaging (MRI). The utilisation of these materials as contrast agents offers several advantages including lower toxicity, prolonged circulation time, and a sufficiently high Gd content, thereby enhancing disease imaging during MRI diagnosis. Therefore, this study synthesised Gd NPs using the hydrothermal method based on the response surface methodology Box-Behnken design (RSM-BBD) to determine the optimal conditions. In this experimental design, three independent variables, the mass of Gd₂O₃ (g), the synthesis temperature (°C) and time (h), were optimised to obtain sufficiently sized nanoparticles for further biomedical applications. In addition, polyethene glycol-6000 (PEG-6000) was used as a stabiliser to form uniformly sized nanoparticles. The optimal conditions were 0.4910 g of Gd₂O₃, a temperature of 180 °C, and a synthesis time of 7 h. Characterisation by scanning electron microscope-energy dispersive X-ray (SEM-EDX) and transmission electron microscope (TEM) demonstrated that the Gd NPs were spherical with a size range below 20 nm. Fourier transform infrared (FTIR) spectroscopy identified PEG molecules with low intensity on the Gd NPs and the obtained zeta potential value was +36.7±0.802 mV. The RSM-BBD analysis applied in this study facilitated the determination of the optimal synthesis conditions.

Combination of therapies is a common strategy in cancer treatment. Such combined therapies only have merit provided that there is superior therapeutic outcome with fewer side effects, compared to single therapies. Here, this work explores the possibility to combine chemotherapy with radionuclide therapy using polymeric micelles as a delivery vehicle. For this purpose, this work prepares poly(ε-caprolactone-b-ethylene oxide) (PCL-PEO) micelles and load them simultaneously with paclitaxel (PTX) and ¹⁷⁷Lu(III). This work chooses a 3D tumor spheroid composed of glioblastoma cells (U87) to evaluate the combined treatment. The diffusion of the micelles in the spheroid is investigated by confocal laser scanning microscopy (CLSM) and light-sheet fluorescence microscopy (LSFM). The results show that the micelles are able to penetrate deep into the spheroid within 24 h of incubation and mainly accumulated around or in the lysosomes once in the cell. Subsequently, this work evaluates the cell killing efficiency of the single treatments (PTX or ¹⁷⁷Lu(III)) versus combined treatment (PTX + ¹⁷⁷Lu(III)) by measuring the growth of the spheroids as well as by performing a cell-viability assay. The results indicate that the combined therapy achieves a superior therapeutic outcome with better cell growth inhibition and cell killing efficiency compared to the single treatments.

Radiation therapy has made tremendous progress in oncology over the last decades due to advances in engineering and physical sciences in combination with better biochemical, genetic and molecular understanding of this disease. Local delivery of optimal radiation dose to a tumor, while sparing healthy surrounding tissues, remains a great challenge, especially in the proximity of vital organs. Therefore, imaging plays a key role in tumor staging, accurate target volume delineation, assessment of individual radiation resistance and even personalized dose prescription. From this point of view, radiotherapy might be one of the few therapeutic modalities that relies entirely on high-resolution imaging. Magnetic resonance imaging (MRI) with its superior soft-tissue resolution is already used in radiotherapy treatment planning complementing conventional computed tomography (CT). Development of systems integrating MRI and linear accelerators opens possibilities for simultaneous imaging and therapy, which in turn, generates the need for imaging probeswith therapeutic components. In this review, we discuss the role of MRI in both external and internal radiotherapy focusing on the most important examples of contrast agents with combined therapeutic potential.