Purpose Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A proposed new strategy for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in-situ release after implantation. This in silico study investigates the intra-tumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials An experimentally determined intra-tumoral diffusion coefficient (D) for 10 nm nanoparticles was employed to estimate D for other sizes using the Stoke-Einstein equation. GNP concentration profiles, obtained using D, were then employed to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel using dose-painting by numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation is carried out as a function of GNP size for clinically applicable low dose rate brachytherapy sources: I-125, Pd-103, Cs-131. Results Results showed that dose enhancement to tumor voxels/sub-volumes during brachytherapy can be customized by varying the sizes of GNP released or eluted from the GBS. For example, using 7 mg/g GNP concentration, significant DEF (> 20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNPs sizes of 2 nm, 5 nm, 10 nm, 20 nm, 30 nm 50 nm, and 80 nm when treating with I-125. Conclusions Analyses show that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. The findings provide a useful reference for further work towards potential development of a new brachytherapy application with in-situ dose-painting administered via gold-nanoparticle eluters, for prostate cancer.

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated both on the right and left flank of each mouse, with the left tumor representing metastasis. The mice were randomized and divided into eight cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another similar four cohorts at 0 Gy. IGRT and Computed Tomography (CT) imaging were performed using a small animal radiation research platform (SARRP). Tumor volume measurements for both flank tumors and animal survival was assessed over 25 weeks. Tumor volume measurements showed significantly enhanced inhibition in growth for the right flank tumors of mice in the cohort treated with SRBs loaded with CD40 mAbs and IGRT. Results also suggest that the use of polymeric SRBs with CD40 mAbs without RT could generate an immune response, consistent with previous studies showing such response when using anti-CD40. Overall, 60% of mice treated with SRBs showed complete tumor regression during the observation period, compared to 10% for cohorts administered with anti-CD40 mAbs, but no SRB. Complete tumor regression was not observed in any other cohorts. The findings justify more studies varying RT doses and quantifying the immune-cell populations involved when using SRBs. Such SRBs could be developed to replace currently used RT biomaterials, allowing not only for geometric accuracy during RT, but also for extending RT to the treatment of metastatic lesions.

No abstract