PEGylated gold nanostars (pAuNSs) and their radioactive surrogate (¹¹¹In–DTPA–pAuNS), with unique physiochemical properties, are thought to be a promising agent for image-guided photothermal therapy (PTT).

Colorectal cancer is one of the major causes of cancer-related death in Taiwan and worldwide. Patients with peritoneal metastasis from colorectal cancer have reduced overall survival and poor prognosis. Hybrid protein-inorganic nanoparticle systems have displayed multifunctional applications in solid cancer theranostics. In this study, a gold nanocore-encapsulated human serum albumin nanoparticle (Au@HSANP), which is a hybrid protein-inorganic nanoparticle, and its radioactive surrogate ¹¹¹In-labeled Au@HSANP (¹¹¹In-Au@HSANP), were developed and their biological behaviors were investigated in a tumor/ascites mouse model. ¹¹¹In-Au@HSANP was injected either intravenously (iv) or intraperitoneally (ip) in CT-26 tumor/ascites-bearing mice. After ip injection, a remarkable and sustained radioactivity retention in the abdomen was noticed, based on microSPECT images. After iv injection, however, most of the radioactivity was accumulated in the mononuclear phagocyte system. The results of biodistribution indicated that ip administration was significantly more effective in increasing intraperitoneal concentration and tumor accumulation than iv administration. The ratios of area under the curve (AUC) of the ascites and tumors in the ip-injected group to those in the iv-injected group was 93 and 20, respectively. This study demonstrated that the ip injection route would be a better approach than iv injections for applying gold-albumin nanoparticle in peritoneal metastasis treatment.

Cartilage damage, a common cause of osteoarthritis, requires medical imaging for accurate diagnosis of pathological changes. However, current instruments can acquire limited imaging information due to sensitivity and resolution issues. Therefore, multimodal imaging is considered an alternative strategy to provide valuable images and analyzes from different perspectives. Among all biomaterials, gold nanomaterials not only exhibit outstanding benefits as drug carriers, in vitro diagnostics, and radiosensitizers, but are also widely used as contrast agents, particularly for tumors. However, their potential for imaging cartilage damage is rarely discussed. In this study, we developed a versatile iodinated gadolinium-gold nanomaterial, AuNC@BSA-Gd-I, and its radiolabeled derivative, AuNC@BSA-Gd-131I, for cartilage detection. With its small size, negative charge, and multimodal capacities, the probe can penetrate damaged cartilage and be detected or visualized by computed tomography, MRI, IVIS, and gamma counter. Additionally, the multimodal imaging potential of AuNC@BSA-Gd-I was compared to current multifunctional gold nanomaterials containing similar components, including anionic AuNC@BSA, AuNC@BSA-I, and AuNC@BSA-Gd as well as cationic AuNC@CBSA. Due to their high atomic numbers and fluorescent emission, AuNC@BSA nanomaterials could provide fundamental multifunctionality for imaging. By further modifying AuNC@BSA with additional imaging materials, their application could be extended to various types of medical imaging instruments. Nonetheless, our findings showed that each of the current nanomaterials exhibited excellent abilities for imaging cartilage with their predominant imaging modalities, but their versatility was not comparable to that of AuNC@BSA-Gd-I. Thus, AuNC@BSA-Gd-I could be served as a valuable tool in multimodal imaging strategies for cartilage assessment.

The Ras/PI3K/ERK signaling network is frequently mutated and overactivated in various human cancers. Focal adhesion kinase (FAK) is commonly overexpressed in several cancer types and has been implicated in treatment resistance mechanisms. A positive feedback loop between Ras, PI3K, the cytoskeleton, and FAK was previously shown to drive Ras signaling excitability. In this study, we investigated the effectiveness of targeting Ras signaling excitability by concurrently inhibiting FAK and PI3K in cervical and pancreatic cancer cells, which depend on activation Ras/PI3K signaling. We found that the combination of FAK and PI3K inhibitors synergistically suppressed the growth of cervical and pancreatic cancer cell lines through increased apoptosis and decreased mitosis. PI3K inhibitors alone caused only a transient suppression of downstream AKT activity and paradoxically increased FAK signaling in cancer cells. The addition of an FAK inhibitor effectively counteracted this PI3K-inhibitor-induced FAK activation. Furthermore, PI3K inhibitors were found to activate multiple receptor tyrosine kinases (RTKs), including insulin receptor, IGF-1R, EGFR, HER2, HER3, AXL, and EphA2. Taken together, our results suggest that FAK inhibition is necessary to counteract the compensatory RTK activation induced by PI3K inhibitors, thereby achieving more effective suppression of cancer cell growth. These findings highlight the therapeutic potential of combined FAK and PI3K inhibition in cancer treatment.

Fibroblast activation protein (FAP) is overexpressed in a variety of cancers, making it an attractive target for bifunctional chelator-based radiopharmaceuticals. This study initially aimed to assess the effect of chelator structure on the biodistribution of ²⁰³Pb/²¹²Pb-labeled FAP inhibitor (FAPI) bioconjugates. However, suboptimal in vivo biodistribution and imaging results suggested the bioconjugate was unstable. RadioHPLC analysis of urine samples suggest the thiourea bond, formed during conjugation between an amine on the biomolecule, and an isothiocyanate-functionalized chelator, is unstable in vivo, resulting in detachment of the radiometal-chelator complex from the targeting vector, resulting in poor tumor accumulation. To determine whether this instability was specific to the FAPI system, a peptide-based (Cyclic melanocyte stimulating hormone, CycMSH) bioconjugate targeting the melanocortin-1 receptor was synthesized using the same thiourea linkage. Identical metabolites were observed, supporting the hypothesis that thiourea bonds are unstable in vivo with this theranostic isotope pair. Subsequently, the effect of bioconjugation chemistry, specifically thiourea and amide bonds, on the stability and biodistribution of ²⁰³Pb/²¹²Pb-labeled bioconjugates was assessed. Modifying the bioconjugation linker to be an amide bond, formed by utilizing a chelate containing an active ester instead of an isothiocyanate, led to significantly improved in vitro and in vivo stability, as demonstrated by radioHPLC and biodistribution and imaging studies in both models. These findings highlight the importance of the choice of bioconjugation chemistry in the development of lead-based radiopharmaceuticals and emphasize the importance of selecting stable linkages to ensure optimal radiometal retention and tumor targeting.