Search Results (15)

Background/Objectives: Magnetic nanoparticles have emerged as powerful tools for biomedical imaging, targeted drug delivery, and hyperthermia therapy. Magnetic particle imaging (MPI) is among the most promising technologies built around its properties: a radiation-free, quantitative tomographic modality that detects superparamagnetic iron oxide nanoparticles (SPIONs) directly against a biologically silent background. This review synthesizes MPI’s physical principles, nanoparticle design strategies, and preclinical applications within the broader landscape of magnetic material engineering for biomedical use. Methods: A systematic review was conducted covering MPI signal generation and image reconstruction, nanoparticle core synthesis and surface coating approaches, and preclinical applications, spanning cell tracking, oncological imaging, vascular perfusion, neuroimaging, and MPI-guided theranostics. Studies were selected to provide quantitative benchmarks and direct comparisons with competing modalities where available. Results: MPI delivers signal-to-background ratios above 1000:1, iron-mass linearity at R² ≥ 0.99, regardless of tissue depth, and acquisition rates up to 46 volumes per second. Tracer architecture—encompassing single-core particles, multicore nanoflowers, and stimuli-responsive cluster designs—is the primary determinant of sensitivity, environmental robustness, and theranostic capability. Preclinical results include detection of cell populations in the low thousands, earlier ischaemia identification than diffusion-weighted MRI, real-time drug release quantification, and spatially confined tumour hyperthermia. Three translational bottlenecks are identified: the absence of a clinically approved tracer with optimal relaxation dynamics, hardware performance losses when scaling to human-bore systems, and overestimation of passive tumour accumulation in murine models. Conclusions: MPI illustrates how progress in magnetic material design directly expands clinical imaging and theranostic possibilities. Successful translation will require indication-driven, interdisciplinary development that integrates materials science, scanner engineering, and regulatory strategy in parallel. Full article

Objectives: This study aimed to evaluate the setup accuracy and intrafractional geometric stability of surface-guided radiation therapy (SGRT) under frameless immobilization in lung cancer radiotherapy and to assess its clinical utility in a relatively large patient cohort. Materials and Methods: A total of 678 treatment fractions from 52 patients with primary non-small cell lung cancer (NSCLC), treated between October 2024 and November 2025, were retrospectively analyzed. Patient setup was performed using SGRT with the Identify system, and cone-beam computed tomography (CBCT) served as the reference for internal target localization Intrafractional setup displacements, center-of-mass (COM) shifts, residual setup errors, and intrafractional clinical target volume (CTV) variations were evaluated. Spatial agreement between planned and intrafractional tumor volumes was quantified using the Dice Similarity Coefficient (DSC). Results: The mean CBCT-based intrafractional shifts were −0.01 mm (vertical), 0.03 mm (longitudinal), and 0.01 mm (lateral), indicating negligible systematic errors. The greatest variability was observed in the longitudinal direction (standard deviation, 1.32 mm), with a maximum displacement of 4.58 mm. COM-based analysis demonstrated near-zero mean displacements in all directions, with standard deviations ranging from 0.01 to 0.02 mm. DSC values ranged from 0.91 to 0.98, with a mean of 0.96, indicating excellent spatial agreement between planned and intrafractional tumor volumes. Residual setup errors were predominantly within ±1 mm, and the mean intrafractional CTV volume change was minimal (0.27 cm³). Conclusions: SGRT-based frameless lung cancer radiotherapy demonstrated high setup accuracy and robust intrafractional geometric stability. Although slightly greater variability was observed in the longitudinal direction, overall positional deviations and volumetric changes remained within clinically acceptable limits. These findings support the feasibility of integrating SGRT with CBCT-guided radiotherapy and suggest potential benefits for workflow efficiency and planning target volume margin optimization. Full article

Background: Boron neutron capture therapy (BNCT) represents a highly selective therapeutic modality for recalcitrant cancers, leveraging the nuclear reaction initiated by thermal neutron capture in boron-10 (¹⁰B) to deliver high-linear energy transfer radiation (α-particles and ⁷Li ions) directly within tumor cell boundaries. However, the widespread clinical adoption of BNCT is critically hampered by the pharmacological challenge of achieving sufficiently high, tumor-selective intracellular ¹⁰B concentrations (20–50 μg of ¹⁰B/g tissue). Conventional small-molecule boron carriers often exhibit dose-limiting non-specificity, rapid systemic clearance, and poor cellular uptake kinetics. Methods: To overcome these delivery barriers, we synthesized and characterized a novel dual-modality nanoplatform based on highly biocompatible, functionalized graphene oxide (GO). This platform was structurally optimized via covalent conjugation with high-boron content carborane clusters (dodecacarborane derivatives) for enhanced BNCT efficacy. Crucially, the nanocarrier was further decorated with plasmonic gold nanostructures (AuNPs), endowing the system with intrinsic surface-enhanced Raman scattering (SERS) properties, enabling real-time, high-resolution intracellular tracking and quantification. Results: We evaluated the synthesized GO@Carborane@Au nanoplatforms for their stability, cytotoxicity, and internalization characteristics. Cytotoxicity assays demonstrated excellent biocompatibility against the non-malignant human keratinocyte line (HaCaT) while showing selective toxicity (upon irradiation, if tested) and high cellular uptake efficiency in the aggressive human glioblastoma tumor cell line (T98G). The integrated plasmonic component allowed for the successful, non-destructive monitoring of nanoplatform delivery and accumulation within both HaCaT and T98G cells using SERS microscopy, confirming the potential for pharmacokinetic and biodistribution studies in vivo. Conclusions: This work details the successful synthesis and preliminary in vitro validation of a unique graphene oxide-based dual-modality nanoplatform designed to address the critical delivery and monitoring challenges of BNCT. By combining highly efficient carborane delivery with an integrated photonic trace marker, this system establishes a robust paradigm for next-generation theranostic agents, significantly advancing the potential for precision, image-guided BNCT for difficult-to-treat cancers like glioblastoma. Full article

Purpose: This study aimed to compare QoL outcomes among patients undergoing active breathing control (ABC), voluntary deep inspiration breath hold (vDIBH), and surface-guided radiation therapy (SGRT). Methods: This was a non-randomized, three-arm clinical trial in which 55 patients were sequentially allocated to ABC (n = 19), SGRT (n = 20), or vDIBH (n = 16). QoL was assessed using the European Organization for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30) at baseline, treatment completion, and 6–8 weeks post-treatment. Linear regression was used to compare changed scales in QoL domains across groups. A p-value of <0.05 was considered statistically significant. Results: Baseline QoL scores were high across all groups, with physical functioning being the highest-rated domain and global health status the lowest. Fatigue, pain, and insomnia were the most highly reported symptoms at all time points. At 6–8 weeks, social functioning improved significantly in SGRT compared to vDIBH (16.67 vs. −12.50, p = 0.0053). Patients in the vDIBH group reported significantly increased pain compared to ABC at 6–8 weeks (p = 0.0240). No other significant differences were observed in QoL changes between the groups. Conclusions: The three breath-hold techniques maintained overall QoL with no differences between the groups, except for pain between vDIBH and ABC and social functioning for vDIBH and SGRT both at 6–8 weeks of follow-up. Despite the limitations of this study, each breath-hold technique has demonstrated comparable impact on QoL in patients with left-sided breast cancer and each could be used as a viable option with respect to QoL. Full article

Background: Gross tumor volume (GTV) segmentation of Nasopharyngeal Carcinoma (NPC) crucially determines the precision of image-guided radiation therapy (IGRT) for NPC. Compared to other cancers, the clinical delineation of NPC is especially challenging due to its capricious infiltration of the adjacent rich tissues and bones, and it routinely requires multimodal information from CT and MRI series to identify its ambiguous tumor boundary. However, the conventional deep learning-based multimodal segmentation method suffers from limited prediction accuracy and frequently performs as well as or worse than single-modality segmentation models. The limited multimodal prediction performance indicates defective information extraction and integration from the input channels. This study aims to develop a 3D Gaussian-prompted Diffusion Model (3DG-PDM) for more clinically targeted information extraction and effective multimodal information integration, thereby facilitating more accurate and clinically interpretable GTV segmentation for NPC. Methods: We propose a 3D-Gaussian-Prompted Diffusion Model (3DGS-PDM) that operates NPC tumor contouring in multimodal clinical priors through a guided stepwise process. The proposed model contains two modules: a Gaussian Initialization Module that utilizes a 3D-Gaussian-Splatting technique to distill 3D-Gaussian representations based on clinical priors from CT, MRI-t2 and MRI-t1-contract-enhanced-fat-suppression (MRI-t1-cefs), respectively, and a Diffusion Segmentation Module that generates tumor segmentation step-by-step from the fused 3D-Gaussians prompts. We retrospectively collected data on 600 NPC patients from four hospitals through paired CT, MRI series and clinical GTV annotations, and divided that dataset into 480 training volumes and 120 testing volumes. Results: Our proposed method can achieve a mean dice similarity cofficient (DSC) of 84.29 ± 7.33, a mean average symmetric surface distance (ASSD) of 1.31 ± 0.63, and a 95th percentile of Hausdorff (HD₉₅) of 4.76 ± 1.98 on primary NPC tumor (GTVp) segmentation, and a DSC of 79.25 ± 10.01, an ASSD of 1.19 ± 0.72 and an HD₉₅ of 4.76 ± 1.71 on metastasis NPC tumor (GTVnd) segmentation. Comparative experiments further demonstrate that our method can significantly improve the multimodal segmentation performance on NPC tumors, with superior advantages over five other state-of-the-art comparative methods. Visual evaluation on the segmentation prediction process and a three-step ablation study on input channels further demonstrate the interpretability of our proposed method. Conclusions: This study proposes a performant and interpretable multimodal segmentation method for GTV of NPC, contributing greatly to precision improvement for NPC therapy treatment. Full article

The advent of nanotechnology has revolutionized the field of medicine, particularly in the development of targeted therapeutic strategies. Among these, radiolabeled nanomaterials have emerged as promising tools for both diagnostic and therapeutic applications, offering precise delivery of radiation to diseased tissues while minimizing damage to healthy ones. Notably, Lutetium-177 (¹⁷⁷Lu) has gained significant attention due to its favorable emission properties and availability that render it suitable for imaging and therapeutic purposes. When integrated with magnetic nano-formulations, ¹⁷⁷Lu-labeled systems combine the benefits of targeted radiation therapy (TRT) with the unique properties of magnetic nanoparticles (MNPs), such as magnetic resonance imaging (MRI) contrast enhancement and magnetically guided drug delivery to address challenges in diagnosis and treatment of diseases, such as cancer. By examining the latest advancements in their design, particularly surface functionalization and bioconjugation strategies, this study aims to highlight their efficacy in targeted therapy, imaging, and theranostic applications. Furthermore, we discuss the current challenges, such as scalability, biocompatibility, and regulatory hurdles, while proposing future directions to enhance their clinical translation. This comprehensive review underscores the transformative potential of ¹⁷⁷Lu-labeled magnetic nano-formulations in precision medicine and their role in shaping the future of therapeutic interventions. Full article

This study aimed to evaluate the placement accuracy and reproducibility of Surface Guided Radiotherapy (SGRT) compared with the conventional tattoo/laser method in patients undergoing radiotherapy for abdominal malignancies. A retrospective analysis was conducted on 43 patients treated with either SGRT (Group A) or the tattoo/laser technique (Group B). Patients in both groups underwent CBCT to quantify the positioning shifts in the vertical (Svrt), lateral (Slat) and longitudinal (Slng) axes, as well as the total shift. Statistical indicators including median, interquartile range (IQR), and range were calculated, and Mann–Whitney U tests were performed due to non-normal data distribution. Median values in all axes were same between groups: Svrt = 0.4 cm, Slat = 0.2 cm, Slng = 0.4 cm. Group A showed a higher total median shift equal to 0.8 cm versus 0.7 cm of Group B. However, IQRs were smaller in the Group B for all directions and total shift, indicating greater method consistency. Statistically significant differences (p < 0.05) were observed in all axes, except the vertical. These findings suggest that, while SGRT achieves comparable median alignment, its use in a highly variable anatomical region such as the abdomen may be associated with greater setup variability. Full article

Nosocomial infections caused by Candida albicans pose serious challenges to healthcare systems due to their persistence on medical surfaces and resistance to conventional disinfectants. This study evaluates antifungal properties of SnO₂ doped with silver and cuprite nanoparticles and WO₃ thin films, as well as cobalt (CoFe₂O₄) and cobalt–nickel (Co_0.5Ni₀.₅Fe₂O₄) ferrite nanoparticles, activated by ultraviolet C (UVC) radiation, direct electric current (up to 100 V), and magnetic fields. SnO₂ films were synthesized by Spray Pyrolysis and WO₃ by Sputtering deposition, Ferrites nanoparticles by sol–gel, while metallic nanoparticles were synthetized via chemical reduction. Characterization consisted mainly of SEM, TEM, and XRD, and their antimicrobial activity was tested against C. albicans. WO₃ films achieved 86.2% fungal inhibition after 5 min of UVC exposure. SnO₂ films doped with nanoparticles reached 100% inhibition when combined with UVC and 100 V. Ferrite nanoparticles alone showed moderate activity (21.9%–40.4%) but exhibited strong surface adhesion to fungal cells, indicating potential for magnetically guided antifungal therapies. These results demonstrate the feasibility of using multifunctional nanomaterials for rapid, non-chemical disinfection. The materials are low-cost, scalable, and adaptable to hospital settings, making them promising candidates for reducing healthcare-associated fungal infections through advanced surface sterilization technologies. Full article

Over the past decade, numerous innovative immunotherapy strategies have transformed the treatment of cancer and improved the survival of patients unresponsive to conventional chemotherapy and radiation therapy. Immune checkpoint inhibition approaches aim to block negative regulatory pathways that limit the function of endogenous T cells, while adoptive cell therapy produces therapeutic T cells with high functionality and defined cancer specificity. While CAR engineering successfully targets cancer surface antigens, TCR engineering enables targeting of the entire cancer proteome, including mutated neo-antigens. To date, TCR engineering strategies have focused on the identification of target cancer antigens recognised by well-characterised therapeutic TCRs. In this review, we explore whether antigen-focused approaches could be complemented by TCR-focused approaches, whereby information of the TCR repertoire of individual patients provides the basis for selecting TCRs to engineer autologous T cells for adoptive cell therapy. We discuss how TCR clonality profiles, distribution in T cell subsets, and bioinformatic screening against continuously improving TCR databases can guide the selection of TCRs for therapeutic application. We further outline in vitro approaches to prioritise TCR candidates to confirm cancer reactivity and exclude recognition of healthy autologous cells, which could provide validation for their therapeutic use even when the target antigen remains unknown. Full article

Objectives: Surface-Guided Radiation Therapy (SGRT) has been widely adopted in breast cancer radiotherapy, particularly for improving setup accuracy and motion management. Recently, its application in lung cancer has attracted growing interest due to similar needs for precision. This study investigates the feasibility and clinical utility of SGRT in lung cancer treatment, focusing on its effectiveness in patient setup and real-time motion monitoring under frameless immobilization conditions. Materials and Methods: A total of 204 treatment records from 17 patients with primary lung cancer who underwent radiotherapy at Korea University Guro Hospital between October 2024 and April 2025 were retrospectively analyzed. Patients were initially positioned using the Identify system (Varian) in the CT suite, with surface data transferred to the treatment room system. Alignment was performed to within ±1 cm and ±2° across six degrees of freedom. Cone-beam CT (CBCT) was acquired prior to treatment for verification, and treatment commenced when the Distance to Correspondence Surface (DCS) was ≤0.90. Setup deviations from the Identify system were recorded and compared with CBCT in three translational axes to evaluate positioning accuracy and PTV displacement. Results and Conclusions: The Identify system was shown to provide high setup accuracy and reliable real-time motion monitoring in lung cancer radiotherapy. Its ability to detect patient movement and automatically interrupt beam delivery contributes to enhanced treatment safety and precision. In addition, even though the maximum longitudinal (Lng) shift reached up to −1.83 cm with surface-guided setup, and up to 1.78 cm (Lat) 5.26 cm (Lng), 9.16 cm (Vrt) with CBCT-based verification, the use of Identify’s auto-interruption mode (±1 cm in translational axes, ±2° in rotational axes) allowed treatment delivery with PTV motion constrained within ±0.02 cm. These results suggest that, due to significant motion in the longitudinal direction, appropriate PTV margins should be considered during treatment planning. The Identify system enhances setup accuracy in lung cancer patients using a surface-guided approach and enables real-time tracking of intra-fractional errors. SGRT, when implemented with systems such as Identify, shows promise as a feasible alternative or complement to conventional IGRT in selected lung cancer cases. Further studies with larger patient cohorts and diverse clinical settings are warranted to validate these findings. Full article

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade. Full article

Background/Objectives: To overcome the side effects of conventional cancer treatment, multifunctional nanoparticles with image-guidance properties are increasingly desired to obtain enhanced therapeutic efficacy without any toxicity of the treatment. Herein, we introduce the potential of Polydopamine Radioimmunotherapy with Image-guided Monitoring and Enhanced (drug) Release System (PRIMERS) to meet the challenges of currently used cancer therapy. Methods: The PDA nanobowls were synthesized using an emulsion-induced interfacial anisotropic assembly method followed by surface modification with high-Z material to obtained the final product PRIMERS. Results: The engineered multifunctional nanosystem “PRIMERS” could serve as fiducial markers with the potential for use in combination cancer therapy. By leveraging the advantages of the excellent surface functionalization capability of PDA, the anisotropic nanostructure (PDA nanobowls) has been successfully functionalized with gadolinium, which shows strong MRI contrast signal both in vitro in phantom and in vivo in animals. The results of anti-cancer drug loading and releasing efficiency of these functionalized nanobowls are presented. Moreover, the gadolinium-coated PDA nanobowls demonstrate the capacity for loading immunotherapy drugs (Anti-CD40) with activated release in acidic pH levels characteristic of the tumor microenvironment, with enhanced release following administration of radiation therapy in vitro. Conclusions: Overall, the results highlight the potential of this new technology for combining radiotherapy with activated image-guided drug delivery, which offers broad opportunities to overcome current challenges in cancer treatment. Full article

The peculiar and rare clinical condition below clearly requires a customized care approach in the context of personalized medicine. An 80-year-old female patient who was subjected in 2018 to surgical removal of a cutaneous Merkel cell carcinoma (MCC) nodule located on the posterior surface of the left thigh and to three subsequent palliative radiotherapy treatments developed a fourth relapse in October 2020, with fifteen nodular metastases located in the left thigh and leg. Since the overall macroscopic disease was still exclusively regionally located and microscopic spread was likely extended also to clinically negative skin of the thigh and leg, we performed an irradiation of the whole left lower extremity. For this purpose the total target (65.5 cm) was divided into three sub-volumes. Dose prescription was 30 Gy in 15 daily fractions. A sequential boost of 10 Gy in 5 daily fractions was planned for macroscopic nodules. Plans were calculated by means of volumetric modulated arc therapy (VMAT) with the field overlap technique. Thanks to this, we obtained a homogeneous dose distribution in the field junction region; avoidance structures were delineated in the central part of the thigh and leg with the aim of achieving an optimal superficial dose painting and to reduce bone exposure to radiation. This case study demonstrates that VMAT allows for a good dose coverage for circumferential cutaneous targets while sparing deeper organs at risk. A reproducible image-guided set-up is fundamental for an accurate and safe dose delivery. However, local treatments such as radiotherapy for very advanced MCC of the lower extremities might have limited impact due to the high probability of systemic progression, as illustrated in this case. Radiation is confirmed as being effective in preventing MCC nodule progression toward skin wounding. Full article

Aim: To test inter-fraction reproducibility, intrafraction stability, technician aspects, and patient/physician’s comfort of a dedicated immobilization solution for Brain Linac-based radiation therapy (RT). Methods: A pitch-enabled head positioner with an open-face mask were used and, to evaluate inter- and intrafraction variations, 1–3 Cone-Beam Computed Tomography (CBCT) were performed. Surface Guided Radiation Therapy (SGRT) was used to evaluate intrafraction variations at 3 time points: initial (i), final (f), and monitoring (m) (before, end, and during RT). Data regarding technician mask aspect were collected. Results: Between October 2019 and April 2020, 69 patients with brain disease were treated: 45 received stereotactic RT and 24 conventional RT; 556 treatment sessions and 863 CBCT’s were performed. Inter-fraction CBCT mean values were longitudinally 0.9 mm, laterally 0.8 mm, vertically 1.1 mm, roll 0.58°, pitch 0.59°, yaw 0.67°. Intrafraction CBCT mean values were longitudinally 0.3 mm, laterally 0.3 mm, vertically 0.4 mm, roll 0.22°, pitch 0.33°, yaw 0.24°. SGRT intrafraction mean values were: i_, m_, f_ longitudinally 0.09 mm, 0.45 mm, 0.31 mm; i_, m_, f_ laterally 0.07 mm, 0.36 mm, 0.20 mm; i_, m_, f_ vertically 0.06 mm, 0.31 mm, 0.22 mm; i_, m_, f_ roll 0.025°, 0.208°, 0.118°; i_, m_, f_ pitch 0.036°, 0.307°, 0.194°; i_, m_, f_ yaw 0.039°, 0.274°, 0.189°. Conclusions: This immobilization solution is reproducible and stable. Combining CBCT and SGRT data confirm that 1 mm CTV-PTV margin for Linac-based SRT was adequate. Using open-face mask and SGRT, for conventional RT, radiological imaging could be omitted. Full article

Nanomedicines’ inability to penetrate throughout the entire volume of a tumor due to heterogeneous distribution within the tumor mass remains a crucial limiting factor for a vast range of theranostic applications, including image-guided radiation therapy. Despite many studies conducted on the topic having shown the efficacy and biocompatibility of colloidal gold nanoparticles (GNPs), the biological effects of GNPs in the tumor microenvironment, including the particle–protein interaction and the consequent impact on cellular pathways and contrast enhancement remain unclear. In this regard, further investigations on how GNP surface passivation affects X-ray attenuation as well as in vivo biodistribution will clarify several aspects still under discussion in the scientific community, which so far have limited the clinical translation of their cancer-related applications. We aim to evaluate the influence of protein surface adsorption on the GNP biodistribution in Lewis lung carcinoma (LLC) tumor-bearing mice using high-resolution computed tomography (CT) pre-clinical imaging. We hypothesize that, by controlling the adsorption of proteins on the GNP surface, we can influence the intratumoral distribution and retention of the particles. GNPs approximately 34 nm in diameter were synthesized with a surface plasmon peak at ~530 nm, surface passivated with bovine serum albumin (BSA) to reduce opsonization and improve colloidal stability, and characterized with standard methods. Modulation of BSA adsorption on the GNPs was observed by tuning the pH of the immobilization medium from acidic to alkaline, which we quantified using Langmuir isotherms. CT phantom imaging was used to determine X-ray attenuation as a function of GNP concentration and surface functionalization. The in vitro study for evaluating the uptake of GNPs by LLC cells highlighted a difference in the internalization depending on the surface functionalization. In both cases, macropinocytosis was the trafficking mechanism, but while endosomes with citrate-GNPs can be found in different stages of maturation, cells treated with BSA-GNPs presented larger vesicles up to 1 μm in diameter. The in vivo study was performed by injecting intratumorally, concentrating GNPs into LLC solid tumors grown on the right flank of 6-week-old female C57BL/6 mice. Ten days post-injection, follow-up assessments with CT imaging showed the distribution and retention of the particles in the tumor. CT attenuation quantification based on bioimaging analysis for each time point was conducted. In vivo results showed significant heterogeneity in the intratumoral biodistribution of GNPs dependent on surface passivation. BSA-GNPs perfused predominately along the tumor periphery with few depositions throughout the entire tumor volume. This response can be explained by the abnormal and heterogeneous vascular structure of the LLC tumor, suggesting perfusion rather than permeability as the limiting factor for tumor accumulation of the GNPs. Despite the perivascular cluster accumulation, the BSA-GNP distribution diverged from that obtained after unpassivated, citrate-GNP intratumoral injections. In conclusion, our investigations have shown that surface passivation of GNPs is able to influence the mechanism of cellular uptake in vitro and their in vivo intratumoral diffusion, highlighting the spatial heterogeneity of the solid tumor. Full article