Verification of a simplified aneurysm dimensionless flow parameter to predict intracranial aneurysm rupture status.

OBJECTIVES: Aneurysm number (An) is a novel prediction tool utilising parameters of pulsatility index (PI) and aneurysm geometry. An has been shown to have the potential to differentiate intracranial aneurysm (IA) rupture status. The objective of this study is to investigate the feasibility and accuracy of An for IA rupture status prediction using Australian based clinical data. METHODS: A retrospective study was conducted across three tertiary referral hospitals between November 2017 and November 2020 and all saccular IAs with known rupture status were included. Two sets of An values were calculated based on two sets of PI values previously reported in the literature. RESULTS: Five hundred and four IA cases were included in this study. The results demonstrated no significant difference between ruptured and unruptured status when using An ≥ 1 as the discriminator. Further analysis showed no strong correlation between An and IA subtypes. The area under the curve (AUC) indicated poor performance in predicting rupture status (AUC1=0.55 and AUC2=0.56). CONCLUSIONS: This study does not support An ≥ 1 as a reliable parameter to predict the rupture status of IAs based on a retrospective cohort. Although the concept of An is supported by hemodynamic aneurysm theory, further research is needed before it can be applied in the clinical setting. ADVANCES IN KNOWLEDGE: This study demonstrates that the novel prediction tool, An, proposed in 2020 is not reliable and that further research of this hemodynamic model is needed before it can be incorporated into the prediction of intracranial aneurysm rupture status.

Postamplifying Cas12a Activation through Hybridization Chain Reaction-Triggered Fluorescent Nanocluster Formation for Ultrasensitive Nucleic Acid Detection.

CRISPR/Cas12a-based biosensing is advancing rapidly; however, achieving sensitive and cost-effective reporting of Cas12a activation remains a challenge. In response, we have developed a label-free system capable of postamplifying Cas12a activation by integrating hybridization chain reaction (HCR) and DNA-copper nanoclusters (DNA-CuNCs). The trans-cleavage of Cas12a triggers a silenced HCR, leading to the in situ assembly of fluorescent DNA-CuNCs, allowing for the turn-on reporting of Cas12a activation. Without preamplification, this assay can detect DNA with a detection limit of 5 fM. Furthermore, when coupled with preamplification, the system achieves exceptional sensitivity, detecting the monkeypox virus (MPXV) plasmid at 1 copy in human serum. In a MPXV pseudovirus-based validation test, the obtained results are in agreement with those obtained by qPCR, reinforcing the robustness of this method. Our study represents the first effort to manipulate DNA-CuNC formation on HCR for highly sensitive and cost-effective reporting of Cas12a, resulting in an efficient synthetic biology-enabled sensing platform for biosafety applications.

CRISPR/Cas14 provides a promising platform in facile and versatile aptasensing with improved sensitivity.

CRISPR is reshaping biosensing technology due to its programmability, sensitivity, and specificity. Most current CRISPR-based biosensors are developed based on Cas12 and Cas13, while the biosensing potentials of the newly discovered Cas14 have not been fully elucidated yet. Herein, a fluorometric biosensor named HARRY (highly sensitive aptamer-regulated Cas14 R-loop for bioanalysis) was developed. The diblock ssDNA is designed to contain the activator sequence of Cas14 and the aptamer sequence of specific targets. In the absence of targets, the ssDNA activates Cas14a, then the Cas14a trans-cleavages the fluorescent reporter, causing fluorescence enhancement. In the presence of the targets, ssDNA-target assembly is formed via aptamer interaction, resulting in the inhibition of Cas14a activation. HARRY can detect ATP, Cd2+, histamine, aflatoxin B1, and thrombin with detection limits at the low-nanomolar level, which shows improvement compared with Cas12a-based aptasensors in sensitivity and versatility. We reasoned that the improvement is derived from the ssDNA specificity of Cas14a and found that the detection limit of HARRY is correlated to the binding affinities of aptamers. This study unlocks the potential of Cas14a in versatile aptasensing, which may inspire the development of CRISPR-based biosensors from the Cas14a branch.

Time-resolved fluorescence determination of albumin using ZnGeO:Mn luminescence nanorods modified with polydopamine nanoparticles.

A novel time-resolved fluorescence (TRF) pobe is constructed to detect human serum albumin (HSA) by exploiting ZnGeO:Mn persistent luminescence nanorods (ZnGeO:Mn PLNRs) and polydopamine nanoparticles (PDA NPs). HSA-induced dynamic quenching leads to the fluorescence decrease of ZnGeO:Mn PLNRs, providing the basis for quantitative analysis of HSA. The excellent photo-thermal conversion performance of PDA NPs is helpful to the collision process between ZnGeO:Mn PLNRs and HSA, inducing significant improvement of sensitivity. HSA is quantified by measuring time-resolved fluorescence at 540 nm under excitation of 250-nm light. Under optimal conditions, HSA in the linear range 0.1-100 ng mL-1 are detected by this PDA-mediated ZnGeO:Mn probe with high sensitivity and selectivity, and the detection limit is 36 pg mL-1 (3σ/s). The RSD for the quantification of HSA (5 ng mL-1, n = 11) is 5.2%. The practicability of this TRF probe is confirmed by accurate monitoring HSA contents in urine samples, giving rise to satisfactory spiking recoveries of 96.2-106.0%.

The 100 most cited articles in the endovascular treatment of brain arteriovenous malformations.

BACKGROUND: The literature base for endovascular treatment of brain arteriovenous malformations (BAVMs) has grown exponentially in recent decades. Bibliometric analysis has been used to identify impactful articles in other medical specialties. The aim of this citation analysis was to identify and characterize the top 100 most cited articles in the field of endovascular BAVM treatment. METHODS: The top-cited papers were identified by searching selected keywords ("endovascular treatment," "interventional treatment," "brain arteriovenous malformation," "emboliz(s)ation") on the Web of Science platform. The top 100 articles were ranked according to their number of citations. Each article was further evaluated to obtain predefined characteristics including citation(s) per year, year of publication, authorship, journal-title and impact factor, article topics, article type, and level of evidence. RESULTS: The top 100 most cited articles for endovascular BAVM treatment were published between 1960 and 2014. The total number of citations for these articles ranged from 56 to 471 (median 85.5). Most articles (76%) were published between 1990 and 2009 in three journals (56%), originated in the USA (52%) followed by France (16%). The most common topic related to embolization agents and the majority of articles constituted level IV or V evidence. CONCLUSIONS: This study provides a comprehensive overview of the most cited articles in the field of endovascular BAVM treatment. Our analysis recognizes key contributions from authors and institutions in the field and leads to a better understanding of the evidentiary framework for BAVM treatment.

Rational Engineering of the DNA Walker Amplification Strategy by Using a Au@Ti3C2@PEI-Ru(dcbpy)32+ Nanocomposite Biosensor for Detection of the SARS-CoV-2 RdRp Gene.

The detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for preventing and controlling infectious diseases and disease treatment. In this work, a Au@Ti3C2@PEI-Ru(dcbpy)32+ nanocomposite-based electrochemiluminescence (ECL) biosensor was rationally designed, which realized sensitive detection of the RNA-dependent RNA polymerase (RdRp) gene of SARS-CoV-2. In addition, a DNA walker was also used to excise the hairpin DNAs under the action of Nb.BbvCI endonuclease. Furthermore, model DNA-Ag nanoclusters (model DNA-AgNCs) were used to quench the initial ECL signal. As a result, the ECL biosensor was used to sensitively detect the SARS-CoV-2 RdRp gene with a detection range of 1 fM to 100 pM and a limit of detection of 0.21 fM. It was indicated that the ECL biosensor had a great application potential for clinical medical detection. Furthermore, the DNA walker amplification also played a reliable candidate strategy for other detection methods.

Cardiorespiratory arrest after iso-osmolar iodinated contrast injection: A case report of contrast-induced encephalopathy following contrast-enhanced computed-tomography.

RATIONALE: Contrast-induced encephalopathy (CIE) is a rare complication caused by administration of intravascular contrast media and characterized by acute reversible neurological disturbance. Most of the CIE cases are reported after arterial administration of contrast media such as during cerebral or coronary angiographies, yet only a few articles have reported CIE secondary to intravenous contrast. A case of CIE secondary to intravenous contrast administration is reported here. PATIENT CONCERNS: A 68-year-old man was admitted to our hospital for contrast-enhanced chest computed-tomography (CT) examination due to suspected pulmonary nodules. After CT examination, the patient lost consciousness and experienced a cardiorespiratory arrest. An emergency plain brain CT was done immediately which showed abnormal cortical contrast enhancement and cerebral sulci hyperdensity. DIAGNOSES: After excluding other differential diagnoses such as electrolytes imbalance, hypo/hyperglycemia, cardiogenic pathologies and other neurological emergencies such as cerebral hemorrhage, cerebral infarction, the final diagnosis of CIE was made. INTERVENTIONS: The patient was admitted to the intensive care unit for further management. A series of supportive treatments were arranged. OUTCOMES: Follow-up visits at the outpatient clinic showed no lasting neurological deficits. LESSONS: CIE should be considered as 1 of the differential diagnoses for a patient with acute neurologic symptoms after iodinate contrast administration. Neuroradiological imaging examinations are essential to rule out other etiologies such as acute cerebral infarction or intracranial hemorrhage.

Synthesis of a novel 89Zr-labeled HER2 affibody and its application study in tumor PET imaging.

BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues, etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89Zr-labeled HER2 affibody, [89Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. RESULTS: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [89Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2 ± 1.9%, and the radiochemical purity was higher than 95%. The total synthesis time was only 30 min. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe was highly retained in SKOV-3 xenografts even for 48 h. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5% IA/g during 48 h postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels ( ~ 1% IA/g). The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. CONCLUSION: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [89Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.

PET imaging of a 68Ga labeled modified HER2 affibody in breast cancers: from xenografts to patients.

OBJECTIVE: Overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancers provides promising opportunities for imaging and targeted therapy. Developing HER2 targeted positron emission tomography (PET) probes might be benefit for management of the disease. Small high-affinity scaffold proteins, affibodies, are ideal vectors for imaging HER2 overexpressed tumors. Despite of the initial success on development of 18F labeled ZHER2:342 affibody, the tedious synthesis producers, low yields and unfavorable pharmacokinetics may hinder the clinical use. 68Ga is an attractive positron emitter for PET imaging. A simple preparation of 68Ga labeled ZHER2:342 analog, 68Ga-NOTA-MAL-Cys-MZHER2:342, was reported in the study. The in vivo performances of the tracer for assessing HER2 status in breast cancers were also evaluated. METHODS: NOTA-MAL conjugated Cys-MZHER2:342 was radiolabeled with 68Ga. The probe was evaluated by in vitro tests including stability and cell binding studies in breast cancer cells with different HER2 levels. In vivo evaluation was performed in mice bearing tumors using microPET imaging and biodistribution experiments. A PET/CT imaging study was initially performed in patients with breast cancers. RESULTS: The tracer was synthesized in a straightforward chelation method with satisfactory non-decay corrected yield (81±5%) and radiochemical purity (>95%). In vivo micro-PET imaging showed that HER2 high levels expressed BT474 xenografts were more clear visualized than HER2 low levels expressed MCF-7 tumors (16.12 ± 2.69 ID%/g vs 1.32 ± 0.19 ID%/g at 1 h post-injection). The outcome was consistent with the immunohistochemical analysis. No significant radioactivity was accumulated in healthy tissues (less than 2% ID/g) except kidneys. In a preliminary clinical study, 68Ga-NOTA-MAL-Cys-MZHER2:342 PET imaging allowed more high-contrast detection of HER2 positive primary tumors (maximum standardized uptake value = 2.16±0.27) than those in HER2 negative primary focus (maximum standardized uptake value = 0.32±0.05). No detectable side-effects were found. CONCLUSION: In summary, this study indicates the significant efficiency of the 68Ga labeled HER2 affibody. Preclinical and clinical studies support the possibility of monitoring HER2 levels in breast cancers using 68Ga-NOTA-MAL-Cys-MZHER2:342. ADVANCES IN KNOWLEDGE: The research investigated the feasibility of a 68Ga labeled HER2 affibody modified with a hydrophilic linker for breast cancer PET imaging. Favorable outcomes showed that the probe might be valuable for determining HER2 status of the disease.

Primary thoracic neuroblastoma in an adult: A rare case report.

RATIONALE: Neuroblastoma is one of the most common malignant tumors in childhood, which mainly occurs in adrenal glands and peripheral sympathetic nerve system. Neuroblastoma occurring in adulthood is rare, and adults with neuroblastoma arising from thorax are exceedingly rare. A case of neuroblastoma that originated from thorax was reported, and was treated by resection operation. PATIENT CONCERNS: A 46-year-old woman was admitted to our hospital with left side chest pain for 5 days. Laboratory examinations were all normal. Chest computerized tomogram (CT) showed a lesion with clear boundary that was located at the left dorsal pleura. The nature of the mass was heterogeneous, showing slight heterogeneous enhancement after contrast and there was no obvious necrosis. DIAGNOSES: Based on the morphologic and immunohistochemical features, the tumor diagnosis was favorable for neuroblastoma. INTERVENTIONS: A resection operation was carried out. OUTCOMES: Three years postoperative, no sign of recurrence or metastasis has been observed. LESSONS: Primary neuroblastoma in adulthood is rare and has poor prognosis. Resection can be an important treatment option, and combining with other methods like chemotherapy, stem cell transplantation, the survival rate may be improved.

Nanoparticle ferritin-bound erastin and rapamycin: a nanodrug combining autophagy and ferroptosis for anticancer therapy.

Ferroptosis and autophagy are the two forms of the regulation of cell death that play important roles in cancer therapy. However, little is known about the combination of the therapeutic effects of ferroptosis and autophagy in cancer therapy. Here, in this study, we constructed a novel carrier-free nanodrug called nanoparticle ferritin-bound erastin and rapamycin (NFER). The NFER nanodrug was prepared by the emulsification technique; it exhibited an average size of 78.8 nm and zeta potential of -25.9 ± 3.3 mV. Controllable drug encapsulation efficiency and loading ratios in NFER could be obtained. This nanodrug showed high stability in both water and PBS for several days. The release studies demonstrated that rapamycin and erastin could reach equilibrium after 24 h and 36 h, respectively; the maximum values of the released percentages of both reached beyond 30%. An in vitro study revealed that NFER showed robust ferroptosis-inducing capability by the downregulation of glutathione peroxidase-4 (GPX4) and lipid peroxidation accumulation. The autophagy process induced by rapamycin in NFER also played an important role in strengthening ferroptosis. The selective cancer cell killing ability of NFER was verified in cancer cells and normal cells. The ferroptosis-induced cytotoxicity was confirmed through several ferroptosis and autophagy inhibitors. Furthermore, the NFER nanodrug showed an improved control of tumor recurrence in the 4T1 tumor resection model. In summary, these results demonstrated that NFER exhibited excellent properties as a nanodrug, and the cell death induced by NFER was through an autophagy-associated ferroptosis pathway. This study based on protein nanodrug-induced autophagy-associated ferroptosis would provide a new insight into cancer therapy.

Combinatory effects of vaccinia virus VG9 and the STAT3 inhibitor Stattic on cancer therapy.

The recombinant vaccinia virus VG9 and the STAT3 inhibitor Stattic were combined to kill cancer cells via both oncolytic activity and inhibition of STAT3 phosphorylation in cells. The combinatory anti-tumour activity of these compounds was superior to the activity of VG9 or Stattic alone in vivo. The inhibition of tumour growth occurred via increased apoptosis and autophagy pathways. Furthermore, the combinatory anti-tumour activity was more efficient than that of VG9 or Stattic alone on xenografts, especially in nude mice.

Self-Assembling Nonconjugated Poly(amide-imide) into Thermoresponsive Nanovesicles with Unexpected Red Fluorescence for Bioimaging.

Nonconjugated red fluorescent polymers have been increasingly studied to improve the biocompatibility and penetration depth over conventional fluorescent materials. However, the accessibility of such polymers remains challenging due to the scarcity of nonconjugated fluorophores and lacking relevant mechanism of red-shifted fluorescence. Herein, we discovered that the combination of hydrogen bonding and π-π stacking interactions provides nonconjugated poly(amide-imide) with a large bathochromic shift (>100 nm) from blue-green fluorescence to red emission. The amphiphilic PEGylated poly(amide-imide) derived from in situ PEGylation self-assembled into nanovesicles in water, which isolated the aminosuccinimide fluorophore from the solvents and suppressed the hydrogen bonds formation between aminosuccinimide fluorophores and water. Therefore, the fluorescence of PEGylated poly(amide-imide) in water was soundly retained. Furthermore, the strong hydrogen bonding and hydrophobic interactions with water provided PEGylated poly(amide-imide) with a reversible thermoresponsiveness and presented a concentration-dependent behavior. Finally, accompanied by the excellent biostability and photostability, PEGylated poly(amide-imide) exhibited as a good candidate for cell imaging.

Evaluation of A Novel GLP-1R Ligand for PET Imaging of Prostate Cancer.

BACKGROUND: Glucagon-like peptide 1 receptor (GLP-1R) is an important biomarker for diagnosis and therapy of the endocrine cancers due to overexpression. Recently, in human prostate cancer cell lines the receptor was also observed, therefore it may be a potential target for the disease. 18F-Al-NOTA-MAL-Cys39- exendin-4 holds great promise for GLP-1R. Therefore, the feasibility of the 18F-labeled exendin-4 analog for prostate cancer imaging was investigated. METHODS: New probe 18F-Al-NOTA-MAL-Cys39-exendin-4 was made through one-step fluorination. Prostate cancer PC3 cell xenograft model mice were established to primarily evaluate the imaging properties of the tracer via small animal PET studies in vivo. Pathological studies and Western Blots were also performed. RESULTS: PC-3 prostate xenografts were clearly imaged under baseline conditions. At 30 and 60 min postinjection, the tumor uptakes were 2.90±0.41%ID/g and 2.26±0.32 %ID/g respectively. The presence of cys39-exendin-4 significantly reduced the tumor uptake to 0.82±0.10 %ID/g at 60 min p.i. Findings of ex vivo biodistribution studies were similar to those of in vivo PET imaging. The tumors to blood and muscles were significantly improved with the increase of time due to rapid clearance of the tracer from normal organs. Low levels of radioactivity were also detected in the GLP-1R positive tumor and normal organs after coinjection with excessive unlabeled peptides. Immunohistochemistry and Western Blots results confirmed that GLP-1R was widely expressed in PC-3 prostate cancers. CONCLUSION: 18F-Al labeled exendin-4 analog might be a promising tracer for in vivo detecting GLP-1R positive prostate cancer with the advantage of facile synthesis and favorable pharmacokinetics. It may be useful in differential diagnosis, molecularly targeted therapy and prognosis of the cancers.

Targeting HER2-positive gastric cancer with a novel 18F-labeled ZHER2:342 probe.

To realize the diagnosis of HER2-positive gastric cancer via PET imaging, herein, a new kind of 18F-labeled HER2 affibody probe was created; the bifunctional maleimide derivative 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-MAL) was first coupled to a polypeptide, and the resulting compound was subsequently labeled with the 18FAl complex. The binding characteristics of the probe were assessed using both in vitro studies and in vivo microPET imaging and biodistribution experiments. Immunohistochemical staining was performed to confirm the expression level of HER2 in the studied cell lines and tumors. The probe was successfully produced with the radiochemical purity of more than 95%. The NCI N87 cell-associated radioactivity was 19.31 ± 1.01% AD, and it decreased to 0.83 ± 0.04% AD per 106 cells after blocking HER2 as early as 15 minutes post-incubation (p < 0.05). A competition binding assay between radiolabeled and non-radioactive affibody molecules with NCI N87 indicated that the IC50 was 8.10 nM. The microPET imaging and biodistribution of human gastric cancer xenografts demonstrated that the probe could specifically accumulate in tumors at early time points. Protein detection confirmed a strong HER2 expression in NCIN87 and a weak HER2 expression in SGC7901. In conclusion, 18FAl-NOTA-MAL-Cys-GGGRDN(M0)-ZHER2:342 was successfully prepared via a one-step method. The favorable preclinical data showed specific and effective tumor targeting capacity of the proposed probe; this revealed that the probe proposed herein might have potential application in gastric cancer imaging.

Doxorubicin loaded ferritin nanoparticles for ferroptosis enhanced targeted killing of cancer cells.

In recent years, ferroptosis has been investigated widely as a new form of cell death. Development of nanodrugs for ferroptosis induction in cancer cells may be a promising approach for cancer treatment. Here, we developed a type of nanoparticle consisting of the antitumor drug doxorubicin and exogenous ferritin. The drug loading process did not change the size of ferritin obviously. And this nanoparticle could induce the accumulation of ROS and cell ferroptosis for transferrin receptor overexpressed tumor cell, HT29. The ferroptosis process was also confirmed using inhibitors for ferroptosis. The cytotoxicity of this nanoparticle is similar to that of free DOX. This study provides a new strategy for targeting and killing transferrin receptor overexpressed tumor cells.

Age-related change of GLP-1R expression in rats can be detected by [18F]AlF-NOTA-MAL-Cys39-exendin-4.

The glucagon-like peptide-1 receptor (GLP-1R) has been demonstrated as a potential therapeutic target for some neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. Besides, its distribution and density in brain regions are closely associated with cognition, motor function, learning and memory. Given the relationship between age and these neurological diseases, we firstly examined the influences of age on GLP-1R expression using [18F]AlF-NOTA-MAL-Cys39-exendin-4 microPET imaging. The image showed that GLP-1R expression in nearly all regions of the brain of aged rats was evidently lower than that of normal rats. Significant differences were found in olfactory, striatum, hypothalamus, substantial nigra, and hippocampus, which have inseparable relations with some mental and neurological diseases such as PD and AD. Data obtained from biodistribution and immunohistochemistry staining also confirmed the image results. Taken together, these results illustrated decreased expression of GLP-1R in the brain of aged rats can be detected by [18F]AlF-NOTA-MAL-Cys39-exendin-4, which implied GLP-1R as a reliable target and GLP-1R PET imaging could be a promising technology in the field of neurological diseases.

Polyphenol-Poloxamer Self-Assembled Supramolecular Nanoparticles for Tumor NIRF/PET Imaging.

Self-assembled supramolecular nanoparticles have remarkable benefits in bioimaging and drug delivery. Here it is first reported that polyphenol and poloxamer self-assemble supramolecular nanoparticles (PPNPs). PPNPs are fabricated by multivalent hydrogen bonding between tannic acid and Pluronic F-127 together with hydrophobic interactions of poly(propylene oxide) chains, to be applied in tumor near-infrared fluorescence (NIRF) imaging and positron emission tomography (PET) imaging. With near-infrared fluorescent dyes such as IR780 encapsulated via hydrophobic interactions, PPNPs are used in NIRF imaging. PPNPs with excess phenolic hydroxyl groups chelating positron emitting radionuclide 89 Zr function as a PET contrast agent. The in vivo results show surprisingly higher fluorescence intensity in tumors than in other tissues. In addition, PPNPs exhibit good biocompatibility in various cell lines and do not induce hemolysis in vitro. In this study, it is demonstrated that biodegradable and biocompatible PPNPs are an excellent bimodal contrast agent for in vivo tumor imaging.

Theranostic radioiodine-labelled melanin nanoparticles inspired by clinical brachytherapy seeds.

Radioiodine is widely used in nuclear medicine, mainly serving as a tracer and therapeutic agent, and benefits from its various radioactive isotopes of iodine including I-123, I-124, I-125, I-131 and so on. Melanin is a natural material widely dispersed in the human skin, hair and eyes. The excellent biocompatibility and multifunctional abilities of melanin make it a perfect carrier for biomedical applications. Here, we fabricated theranostic radioiodine-labelled melanin nanoparticles (MNPs) through a novel Ag-I two-step method. The Ag-I labelling method for MNP radioiodine-labelling has advantages including a faster labelling time, higher labelling yield, and higher stability than the chloramine-T oxidation method reported previously. The obtained MNP-Ag-131I can be used for both single-photon emission computed tomography and Cherenkov radiation imaging. The ß-rays of 131I also make it a good candidate as a cancer cell killer. The theranostic properties of this nanoparticle were also proved in a xenograft tumor model in vivo. In summary, this study provides a new concept for radioiodine labelling nanoparticles, which can be further investigated in various imaging and radiotherapy applications with different radioactive isotopes of iodine.