Background: The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (¹²⁵I/¹³¹I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with ¹³¹I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with ¹⁸ F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin. Results: SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when ¹³¹I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg ¹³¹I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism. Conclusion: The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials. Graphical

The so-far used Ga-68- or F-18-labelled tracers are of a relative short time window in differentiating tumor fibrosis. SPECT applicable imaging probe, ^99mTc-HYNIC-FAPI-04, was synthesized and evaluated in tumor cells and animal models of FAP-positive glioma and FAP-negative hepatoma, and then compared with ¹⁸F-FDG or ⁶⁸Ga-FAPI-04 PET/CT. The radio-labeling rate of ^99mTc-HYNIC-FAPI-04 was greater than 90%, and the radiochemical purity was >99% after purification with sep-pak C18 column. In vitro cell uptake experiments of ^99mTc-HYNIC-FAPI-04 showed good FAP binding specificity, and the cellular uptake significantly decreased when blocked by DOTA-FAPI-04, reflecting the similar targeting mechanism of HYNIC-FAPI-04 and DOTA-FAPI-04. SPECT/CT imaging showed that U87MG tumor was distinguishable and of a high uptake of ^99mTc-HYNIC-FAPI-04 (2.67 ± 0.35 %ID/mL at 1.5 h post injection (h P.I.), while tumor signal of FAP-negative HUH-7 was as low as 0.34 ± 0.06 %ID/mL. At 5 h P.I., U87MG tumor was still distinguishable (1.81 ± 0.20 %ID/mL). In comparison, although U87MG tumor was of obvious ⁶⁸Ga-FAPI-04 uptake and clearly visible at 1 h P.I., the tumorous radioactive signals were fuzzy at 1.5 h P.I. ^99mTc-HYNIC-FAPI-04 specifically bound to FAP-positive tumors and qualified with the ability of evaluating tumor fibrosis over longer time windows.

A transocular infection has been proved as one of the main approaches that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) invades the body, and angiotensin‐converting enzyme 2 (ACE2) plays a key role in this procedure. Dynamic and quantitative details on virus distribution are lacking for virus prevention and drug design. In this study, a radiotraceable pseudovirus packed with an enhanced green fluorescent protein (EGFP) gene, ¹²⁵I‐CoV, was prepared and inoculated in the unilateral eye of humanized ACE2 (hACE2) mice or ACE2‐knockout (ACE2‐KO) mice. Single‐photon emission computed tomography/computed tomography images were acquired at multiple time points to exhibit ACE2‐dependent procedures from invasion to clearance. Positron emission tomography (PET) and western blot were performed to quantify ACE2 expression and verify the factors affecting transocular infection. For the transocular infection of coronavirus (CoV), the renin–angiotensin–aldosterone system (RAAS), lungs, intestines, and genital glands were the main targeted organs. Due to the specific anchor to ACE2‐expressed host cells, virus concentrations in genital glands, liver, and lungs ranked the top three most and stabilized at 3.75 ± 0.55, 3.30 ± 0.25, and 2.10 ± 0.55% inoculated dose (ID)/mL at 48 h post treatment. Meanwhile, ACE2‐KO mice had already completed the in vivo clearance. In consideration of organ volumes, lungs (14.50 ± 3.75%ID) and liver (10.94 ± 0.71%ID) were the main in‐store reservoirs of CoV. However, the inoculated eye (5.52 ± 1.85%ID for hACE2, 5.24 ± 1.45%ID for ACE2‐KO, p > 0.05) and the adjacent brain exhibited ACE2‐independent virus infection at the end of 72 h observation, and absolute amount of virus played a key role in host cell infection. These observations on CoV infection were further manifested by infection‐driven intracellular EGFP expression. ACE2 PET revealed an infection‐related systematic upregulation of ACE2 expression in the organs involved in RAAS (e.g., brain, lung, heart, liver, and kidney) and the organ that was of own local renin–angiotensin system (e.g., eye). Transocular infection of CoV is ACE2‐dependent and constitutes the cause of disturbed ACE2 expression in the host. The brain, genital glands, and intestines were of the highest unit uptake, potentially accounting for the sequelae. Lungs and liver were of the highest absolute amount, closely related to the respiratory diffusion and in vivo duplication. ACE2 expression was upregulated in the short term after infection with CoV. These visual and quantitative results are helpful to fully understanding the transocular path of SARS‐CoV‐2 and other CoVs.