Xiaoyuan Chen

National Institutes of Health | NIH · National Institute of Biomedical Imaging and Bioengineering (NIBIB)

[This corrects the article DOI: 10.1371/journal.pone.0162601.].

Conspectus"Theranostics" is a portmanteau that links the fields of therapeutics and diagnostics; it describes a personalized medical approach with the expectation to improve the prognosis for cancer patients while reducing the risk of adverse effects that is currently commonly seen for many systemic cancer therapies. Theranostic radioligands can de...

Purpose: Recent studies suggest that 68Ga-FAPI PET/CT demonstrated superiority over 18F-FDG PET/CT in the evaluation of various cancer types, especially in gastric cancer (GC). By comprehensively reviewing and analysing the differences between 68Ga-FAPI and 18F-FDG in GC, some evidence is provided to foster the broader clinical application of FAPI...

Mild photothermal therapy (mPTT) has emerged as a highly promising approach for tumor ablation. However, the heat‐induced overexpression of heat shock proteins (HSPs) limits its efficacy by increasing cellular temperature tolerance. Herein, a self‐catalytically enhanced mild PTT strategy that directly disrupts the structure of HSPs to restore tumor...

Inflammatory diseases (IDs) are a general term that covers all diseases in which chronic inflammation perform as the major manifestation of pathogenesis. Traditional therapies based on the anti‐inflammatory and immunosuppressive drugs and are palliative with the short‐term remission. The emerging of nanodrugs has been reported to solve the potentia...

Molecular fluorophores emitting in the second near‐infrared (NIR‐II, 1000–1700 nm) window with strong optical harvesting and high quantum yields hold great potential for in vivo deep‐tissue bioimaging and high‐resolution biosensing. Recently, J‐aggregates are harnessed to engineer long‐wavelength NIR‐II emitters and show unique superiority in tumor...

Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of lipids and immune cells in plaques built up inside artery walls. Docosahexaenoic acid (DHA, 22:6n-3), an omega-3 polyunsaturated fatty acid (PUFA), which exerts anti-inflammatory and antioxidant properties, has long been purported to be of therap...

The past few decades have witnessed explosive development in drug delivery systems. However, in vivo delivery suffers from non-specific distribution in non-targeted organs or tissues, which may cause undesired side effects and even genotoxicity. Here, we report a general strategy that enables tuning the tropism of polymersomes for liver- and spleen...

Cardiovascular and cerebrovascular diseases (CCVDs) are two major vasculature‐related diseases that seriously affect public health worldwide, which can cause serious death and disability. Lack of targeting effect of the traditional CCVD treatment drugs may damage other tissues and organs, thus more specific methods are needed to solve this dilemma....

Immunotherapy has made remarkable strides in cancer therapy over the past decade. However, such emerging therapy still suffers from the low response rates and immune-related adverse events. Various strategies have been developed to overcome these serious challenges. Thereinto, sonodynamic therapy (SDT), as a non-invasive treatment, has received eve...

Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to d...

ConspectusDevelopment of multifunctional nanoparticles (NPs) with desired properties is a significant topic in the field of nanotechnology and has been anticipated to revolutionize cancer diagnosis and treatment modalities. The surface character is one of the most important parameters of NPs that can directly affect their in vivo fate, bioavailabil...

Acute methicillin resistant Staphylococcus aureus (MRSA) pneumonia is one of the most frequently seen lung infection diseases with high morbidity and mortality. It is urgent to explore an efficient antibacterial strategy owing to the increase of drug resistance, virulence, and pathogenicity of MRSA. It was found that Fe3O4 can induce ferroptosis in...

The role of prostate-specific membrane antigen (PSMA) targeted molecular imaging and radionuclide therapy in prostate cancer is well known. PSMA is also overexpressed in the neovasculature of a number of solid tumors, including renal cell carcinoma (RCC). Several studies have demonstrated the diagnostic utility of PSMA PET imaging in the setting of...

The immunologically “cold” microenvironment of triple negative breast cancer results in resistance to current immunotherapy. Here, we reveal the immunoadjuvant property of gas therapy with cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation to augment aggregation-induced emission (AIE)-active luminogen (AIEgen)-ba...

The metabolic reprogramming of tumors requires high levels of adenosine triphosphate (ATP) to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature helps in tumor ablation, it frequently leads to severe side effects. Therefore, improving the therapeutic response and promoting heal...

Rationale: Early discovery, accurate diagnosis, and staging of lung cancer is essential for patients to receive appropriate treatment. PET/CT has become increasingly recognized as a valuable imaging modality for these patients, but there remains room for improvement in PET tracers. We aimed to evaluate the feasibility of using [⁶⁸Ga]Ga-FAPI-RGD, a...

Fluorescence imaging (FLI), a non‐invasive, real‐time, and highly sensitive imaging modality, allows for investigating the molecular/cellular level activities to understand physiological functions and diseases. The emergence of the second near‐infrared window (NIR‐II, 1000–1700 nm) has endowed fluorescence imaging with deeper tissue penetration and...

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and Arg-Gly-Asp (RGD) peptides have been extensively investigated for imaging of FAP- and integrin αvβ3-positive tumors. In this study, a FAPI-RGD heterodimer was radiolabeled with 68Ga and evaluated in patients with cancer. We hypothesized that the heterodimer, recognizing both FA...

The metabolic reprogramming of tumors requires high levels of adenosine triphosphate (ATP) to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature helps in tumor ablation, it frequently leads to severe side effects. Therefore, improving the therapeutic response and promoting heal...

Purpose Evans blue as an albumin binder has been widely used to improve pharmacokinetics and enhance tumor uptake of radioligands, including prostate-specific membrane antigen (PSMA) targeting agents. The goal of this study is to develop an optimal Evans blue-modified radiotherapeutic agent that could maximize the absolute tumor uptake and tumor ab...

Ferrous iron (Fe ²⁺ ) has more potent hydroxyl radical (⋅OH)‐generating ability than other Fenton‐type metal ions, making Fe‐based nanomaterials attractive for chemodynamic therapy (CDT). However, because Fe ²⁺ can be converted by ferritin heavy chain (FHC) to nontoxic ferric form and then sequestered in ferritin, therapeutic outcomes of Fe‐mediate...

Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood–brain barrier. Therefore,...

Endosomal escape remains a central issue limiting the high protein expression of mRNA therapeutics. Here, we present second near‐infrared (NIR‐II) lipid nanoparticles (LNPs) containing pH activatable NIR‐II dye conjugated lipid (Cy‐lipid) for potentiating mRNA delivery efficiency via a stimulus‐responsive photothermal‐promoted endosomal escape deli...

Endosomal escape remains a central issue limiting the high protein expression of mRNA therapeutics. Here, we present second near‐infrared (NIR‐II) lipid nanoparticles (LNPs) containing pH activatable NIR‐II dye conjugated lipid (Cy‐lipid) for potentiating mRNA delivery efficiency via a s timulus‐responsive p hotothermal‐promoted e ndosomal e scape...

Purpose: Kidney is considered to be one of the dose-limiting organs in peptide receptor radionuclide therapy (PRRT). Amino acid cocktail infusion has been applied to reduce renal absorbed dose by inhibiting the proximal tubular reabsorption of the radiopeptide. An Evans blue-modified 177Lu-labeled octreotate (177Lu-DOTA-EB-TATE) has an extended ci...

Nanomaterials with enzyme‐mimicking properties, coined as nanozymes, are a promising alternative to natural enzymes owing to their remarkable advantages, such as high stability, easy preparation, and favorable catalytic performance. Recently, with the rapid development of nanotechnology and characterization techniques, single atom nanozymes (SAzyme...

Milk-derived extracellular vesicles (mEVs) have been proposed as a potential nanomedicine for intestinal disorders; however, their impact on intestinal barrier integrity in gut inflammation and associated metabolic diseases has not been explored yet. Here, mEVs derived from bovine and human breast milk exert similar protective effects on epithelial...

Atomically precise gold clusters play an important role in the development of high-Z-element-based radiosensitizers, due to their intriguing structural diversity and advantages in correlating structures and properties. However, the synthesis of gold clusters with both water-solubility and single-crystal structure remains a challenge. In this study,...

In vivo crosslinking of nanoparticles is widely used to increase accumulation of therapeutic agents at tumor site for enhanced therapy. However, the components in nanoplatforms usually only play for one role and are independent of each other, unable to amplify their biofunctions. Herein, a complementary functioning tumor microenvironment triggered,...

Emerging as a potent anti-cancer treatment, subcellular targeted cancer therapy has drawn increasing attention, bringing great opportunities for clinical application. In this review, we summarize two targeting strategies for four main subcellular organelles (mitochondria, lysosome, endoplasmic reticulum, and nucleus), including molecule and nanomat...

Ferrous iron (Fe²⁺) has more potent hydroxyl radical (⋅OH)‐generating ability than other Fenton‐type metal ions, making Fe‐based nanomaterials attractive for chemodynamic therapy (CDT). However, because Fe²⁺ can be converted by ferritin heavy chain (FHC) to nontoxic ferric form and then sequestered in ferritin, therapeutic outcomes of Fe‐mediated C...

Rationale: Chemoimmunotherapy is a promising approach in cancer immunotherapy. However, its therapeutic efficacy is restricted by high reactive oxygen species (ROS) levels, an abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME) as well as immune checkpoints for escaping immunosurveillance. Methods: Herein, a new type o...

Nanocatalysts pose great promise as tumor therapeutic agents due to their potent capacity to induce reactive oxygen species (ROS) in tumor microenvironment (TME). Although increasing metal loading can improve the catalytic activity, addressing the dilemma between high metal content and potential systemic biotoxicity it poses still remains a great c...

Ferroptosis has been realized in anticancer drug-induced acute cardiac/kidney injuries (ACI/AKI); however, molecular imaging approach to detect ferroptosis in ACI/AKI is a challenge. We report an artemisinin-based probe (Art-Gd) for contrast-enhanced magnetic resonance imaging of ferroptosis (feMRI) by exploiting the redox-active Fe(II) as a vivid...

Understanding the intricate molecular machinery that governs ferroptosis and leveraging this accumulating knowledge could facilitate disease prevention, diagnosis, treatment, and prognosis. Emerging approaches for the in situ detection of the major regulators and biological events across cellular, tissue, and in living subjects provide a multiscale...

Distinctive upconversion or downshifting of lanthanide nanocrystals holds promise for biomedical and photonic applications. However, either process requires high-energy lasers at discrete wavelengths for excitation. Here we demonstrate that co-sensitization can break this limitation with ultrawide excitation bands. We achieve co-sensitization by em...

The immune checkpoint blockade (ICB) therapy has revolutionized the field of cancer treatment, while low response rates and systemic toxicity limit its clinical outcomes. With the rapid advances in nanotechnology and materials science, various types of biomaterials have been developed to maximize therapeutic efficacy while minimizing side effects b...

Understanding the molecular machinery regulating ferroptosis and leveraging this accumulating knowledge could facilitate disease prevention, diagnosis, treatment, and prognosis. The emerging approaches endowing in situ detection of the major regulators of ferroptosis at the cellular and tissue levels, and in living subjects, provide a multi‐scale p...

The high stability of antibodies and their ability to precisely bind to antigens and endogenous immune receptors, as well as their susceptibility to protein engineering, enable antibody‐based therapeutics to be widely applied in cancer, inflammation, infection, and other disorders. Nevertheless, the application of traditional antibody‐based therape...

Lipid peroxidation (LPO) is one of the most damaging processes in chemodynamic therapy (CDT). Although it is well known that polyunsaturated fatty acids (PUFAs) are much more susceptible than saturated or monounsaturated ones to LPO, there is no study exploring the effect of cell membrane unsaturation degree on CDT. Here, we report a self‐reinforci...

Lipid peroxidation (LPO) is one of the most damaging processes in chemodynamic therapy (CDT). Although it is well known that polyunsaturated fatty acids (PUFAs) are much more susceptible than saturated or monounsaturated ones to LPO, there is no study exploring the effect of cell membrane unsaturation degree on CDT. Here, we report a self‐reinforci...

Ferroptosis plays an important role in tumor inhibition and is a new type of programmed cell death. Recent studies have shown that glutathione (GSH) depletion is an effective method to enhance the therapeutic efficacy of ferroptosis; however, a systematic investigation of the phenomenon is limited. Herein, we provide a facile fluorescence imaging-i...

As a rising generation of nanozymes, single atom enzymes show significant promise for cancer therapy, due to their maximum atom utilization efficiency and well-defined electronic structures. However, it remains a tremendous challenge to precisely produce a heteroatom-doped single atom enzyme with an expected coordination environment. Herein, we dev...

Purpose: Progressive metastatic medullary thyroid carcinoma (MTC) is often characterized by rapid disease progression and poor prognosis, with only few therapeutic options available. Peptide receptor radionuclide therapy (PRRT) has demonstrated remarkable success in the management of gastroenteropancreatic neuroendocrine tumors and has also been s...

Photoimmunotherapy, with spatiotemporal precision and noninvasive property, has provided a novel targeted therapeutic strategy for highly malignant triple‐negative breast cancer (TNBC). However, their therapeutic effect is severely restricted by the insufficient generation of tumor antigens and the weak activation of immune response, which is cause...

Inspired by the attractions of fruit flies to polyamines of rotten food, we developed a facile, bio-orthogonal, supramolecular homing and hunting strategy, relying on the elevated levels of polyamines in tumor as the natural guest cues to attract cucurbit [7] uril (CB[7]) functionalized liposomes to the tumor site, owing to the strong, bio-orthogon...

T cells play a determining role in the immunomodulation and prognostic evaluation of cancer treatments relying on immune activation. While specific biomarkers determine the population and distribution of T cells in tumours, the in situ activity of T cells is less studied. Here we designed T-cell-targeting fusogenic liposomes to regulate and quantif...

Among the few available mRNA delivery vehicles, lipid nanoparticle (LNP) is the most clinically advanced one but requires cumbersome four components and suffers from inflammation‐related side effects which should be minimized for safety. Yet, a certain level of proinflammatory responses and innate immune activation is required to evoke T‐cell immun...

Peptide receptor radionuclide therapy (PRRT) has over the last two decades emerged as a very promising approach to treat neuroendocrine tumors (NETs) with rapidly expanding clinical applications. By chelating a radiometal to a somatostatin receptor (SSTR) ligand, radiation can be delivered to cancer cells with high precision. Unlike conventional ex...

Surgical resection (SR) is the major method for treating invasive or recurrent noninvasive bladder cancer (BC). However, SR still causes additional risks of urinary tract infection, bleeding and some complications that may be life-threatening. Therefore, it is of urgent medical need for new diagnosis and therapy scheme for BC. Herein, we proposed a...

Radiotherapy (RT), including external beam RT and internal radiation therapy, uses high-energy ionizing radiation to kill tumor cells. However, ionizing radiation inevitably damages the surrounding normal tissues. Therefore, it is imperative to develop precision RT for improving the treatment outcome and reducing the adverse effects. Recent breakth...

To surmount the major concerns of commercial small molecule Gd chelates and reported Gd‐based contrast agents (GBCAs) for magnetic resonance imaging (MRI), a new concept of organogadolinium macrochelates (OGMCs) constructed from the coordination between Gd3+ and macromolecules is proposed. A library of macromolecules were screened for Gd3+ coordina...

Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH‐responsive i‐motif DNA‐mediated strategy to tailor the programmable beh...

To investigate the effect of resonant thermal radiation from electric graphene films (GFs) to the immunoactivity of T cells in situ and the benefits to cancer immunotherapy. This work utilizes externally applied GFs to regulate the immunoactivity of T cells through the eminent resonant thermal radiation effect. The GFs are fabricated with high emis...

The therapeutic alliance of ¹⁷⁷Lu radioligand therapy and immune checkpoint blockade (ICB) has gained increasing attention. This study aims to investigate the immunomodulatory effect (targeting‐triggering‐therapy) of ¹⁷⁷Lu‐DOTA‐EB‐cRGDfK (¹⁷⁷Lu‐DER) and to optimize the therapeutic efficacy by combining targeted radionuclide therapy (TRT) and ICB. F...

The development of efficient contrast agents for tumor-targeted imaging remains a critical challenge in the clinic. Herein, we proposed a tumor-derived extracellular vesicle (EV)-mediated targeting approach to improve in vivo tumor imaging using ternary downconversion nanoparticles (DCNPs) with strong near infrared II (NIR-II) luminescence at 1,525...

Fenton reaction-based chemodynamic therapy (CDT), which applies metal ions to convert less active hydrogen peroxide (H2O2) into more harmful hydroxyl peroxide (·OH) for tumor treatment, has attracted increasing interest recently. However, the CDT is substantially hindered by glutathione (GSH) scavenging effect on ·OH, low intracellular H2O2 level,...

We put forward a novel targeting-triggering-therapy (TTT) scheme that combines 64Cu-based targeted radionuclide therapy (TRT) with programmed death-ligand 1 (PD-L1)-based immunotherapy for enhancing therapeutic efficacy. The αvβ3 integrin-targeted 64Cu-DOTA-EB-cRGDfK (64Cu-DER) was synthesized. Flow cytometry, immunofluorescence staining, and RT-qP...