Kam W Leong

Kam W Leong
Duke University | DU

About

567
Publications
72,654
Reads
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41,765
Citations
Citations since 2016
133 Research Items
18330 Citations
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201620172018201920202021202205001,0001,5002,0002,500
201620172018201920202021202205001,0001,5002,0002,500
201620172018201920202021202205001,0001,5002,0002,500

Publications

Publications (567)
Article
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We propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells (APCs) for adoptive cell therapy (ACT). Microfiber scaffolds coated with dendritic cell (DC) membrane replicate physicochemical properties of dendritic cells specific for T cell activation such as rapid recognition by T cells, long duration of T cell tetherin...
Article
Activating macrophages for cancer immunotherapy has attracted intensive attention in recent years, but faces two major challenges. First, tumor-associated macrophages (TAMs) are predominately pro-tumorigenic M2 phenotype. Second, the phagocytosis of macrophages to cancer cells is severely inhibited by the upregulation of ‘don’t eat me’ signals. In...
Article
Photodynamic therapy (PDT) relies on the generation of cytotoxic singlet oxygen (¹O2) from an otherwise nontoxic photosensitizer accumulated in tumor tissue to treat cancer. However, PDT of uveal melanoma, the most common adult intraocular cancer, using potent porphyrin derivatives as photosensitizers has shown limited therapeutic efficacy due to l...
Preprint
Full-text available
Spatially-resolved gene expression profiling provides valuable insight into tissue organization and cell-cell crosstalk; however, spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for a rigorous interpretation of cell states and do not utilize associated his...
Article
Photothermal therapy (PTT) is an effective treatment modality that is highly selective for tumor suppression and is a hopeful alternative to traditional cancer therapy. However, PTT-induced inflammatory responses may result in undesirable side effects including increased risks of tumor recurrence and metastasis. Here we developed multifunctional Mn...
Article
Microbiota-based therapeutics offer innovative strategies to treat inflammatory bowel diseases (IBDs). However, the poor clinical outcome so far and the limited flexibility of the bacterial approach call for improvement. Inspired by the health benefits of probiotics in alleviating symptoms of bowel diseases, we designed bioartificial probiotics to...
Article
MicroRNA (miRNA)-based gene therapy is a robust approach to treating human cancers. However, the low target specificity and safety issues associated with viral vectors have limited the clinical use of miRNA therapeutics. In the present study, we aimed to develop a biocompatible nanocarrier to deliver the tumor suppressor miR-30a-5p for gene therapy...
Article
As a surging public health crisis, obesity and overweight predispose individuals to various severe comorbidities contributed by the accompanying chronic inflammation. However, few options exist for tackling chronic inflammation in obesity or inhibiting depot-specific adiposity. Here, we report that polycationic polyamidoamine (PAMAM) treatment can...
Article
Neural stem cells (NSC) have tremendous potential for therapeutic regeneration of diseased or traumatized neural tissues, including injured spinal cord. However, transplanted NSC suffer from low cell survival and uncontrolled differentiation, limiting in vivo efficacy. Here we tackle this issue by delivery through silk‐collagen protein hydrogels th...
Article
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Chemotherapy, although effective against primary tumors, may promote metastasis by causing the release of proinflammatory factors from damaged cells. Here, polymeric nanoparticles that deliver chemotherapeutics and scavenge proinflammatory factors simultaneously to inhibit chemotherapy‐induced breast cancer metastasis are developed. The cationic na...
Article
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Periodontitis is a common type of inflammatory bone loss and a risk factor for systemic diseases. The pathogenesis of periodontitis involves inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. After establishing the correlation of cell-free DNA (cfDNA) level with periodontitis in patient samp...
Preprint
Full-text available
Carbon nanotubes (CNTs) offer attractive attributes that are useful in innovative biomaterial design for neuroscience research due to their nanoscale features, modifiable chemical functionalities, and tunable electrical properties. In this study, we developed a simple and cost-effective fabrication method for advanced surface-modified cell culture...
Preprint
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Strategies that hijack selective proteins of interest (POIs) to the intracellular protein recycling machinery for targeted protein degradation (TPD) have recently emerged as powerful tools for undruggable targets in biomedical research and the pharmaceutical industry. However, targeting any new POI with current TPD tools requires laborious case-by-...
Preprint
The efficacy of immunotherapeutic treatment protocols to enable immune cell mediated treatment of cancer is significantly modulated in the presence of tumor microenvironment (TME) which is a key factor in providing both a physical barrier and immunosuppressive stimuli. Herein, we developed a recirculating, high-throughput microfluidic cell array to...
Article
Cell reprogramming can satisfy the demands of obtaining specific cell types for applications such as tissue regeneration and disease modeling. Here we report the reprogramming of human fibroblasts to produce chemically-induced osteogenic cells (ciOG), and explore the potential uses of ciOG in bone repair and disease treatment. A chemical cocktail o...
Article
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Living bacteria therapies have been proposed as an alternative approach to treating a broad array of cancers. In this study, we developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery. Based on a small RNA screen of capsular biosynthesis p...
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Radiotherapy is essential for treating unresectable or metastatic breast cancer, but radiotherapy‐induced tumor cell death generates small extracellular vesicles (sEVs) that promote tumor regrowth and metastasis following treatment. Here cationic nanosheets with a high sEVs‐binding capacity that suppress sEVs‐induced tumor regrowth and metastasis f...
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Bacterial infection and excessive inflammation following abdominal injury can cause life‐threatening complications that lead to multiple organ failure and death. Removing bacteria and proinflammatory factors—which are predominantly negatively charged—from the wound site with a cationic, antibiotic‐containing hydrogel wound dressing is therefore a p...
Article
We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shel...
Article
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Conventional approaches to developing biomaterials and implants require intuitive tailoring of process variables, long development cycles, and high expenses. To meet the biomedical and clinical demands, it is critical to accelerate the production of personalized implantable biomaterials and biomedical devices. Building on the Materials Genome Initi...
Article
Inflammation plays an important role in the response to danger signals arising from damage to our body and in restoring homeostasis. Dysregulated inflammatory responses occur in many diseases, including cancer, sepsis and autoimmunity. The efficacy of anti-inflammatory drugs, developed for the treatment of dysregulated inflammation, can be potentia...
Article
Millions of COVID-19 patients have succumbed to respiratory and systemic inflammation. Hyperstimulation of toll-like receptor (TLR) signaling has been shown to be a key driver of immunopathology following infection by viruses. We found that severely ill COVID-19 patients in the Intensive Care Unit (ICU) display hallmarks of such hyper-stimulation w...
Article
A therapeutic strategy that targets multiple proinflammatory factors in inflammatory bowel disease (IBD) with minimal systemic side effects would be attractive. Here, we develop a drug-free, biodegradable nanomedicine that acts against IBD by scavenging proinflammatory cell-free DNA (cfDNA) and reactive oxygen species (ROS). Polyethylenimine (PEI)...
Preprint
Full-text available
DiGeorge Syndrome, or 22q11.2 deletion syndrome (22q11.2 DS), is a genetic disorder caused by microdeletions in chromosome 22, impairing the function of endothelial cells (EC) and/or mural cells and leading to deficits in blood vessel development such as abnormal aortic arch morphology, tortuous retinal vessels, and tetralogy of Fallot. The mechani...
Article
Spinal cord injury (SCI) creates an inflammatory microenvironment characterized by damage-associated molecular patterns (DAMPs) and immune cell activation that exacerbate secondary damage and impair neurological recovery. Here we develop an immunoregulatory hydrogel scaffold for treating SCI that scavenges DAMPs and slowly releases the anti-inflamm...
Article
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Implanted biomaterials have transformed healthcare and the treatment of injury and disease, but their influence on the local immune landscape remains unclear. Here we discovered that degradation-resistant titanium-based implants establish an immunosuppressive microenvironment by recruiting myeloid cells, including monocytes, macrophages, neutrophil...
Article
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The blood–brain barrier (BBB) is important in the normal functioning of the central nervous system. An altered BBB has been described in various neuropsychiatric disorders, including schizophrenia. However, the cellular and molecular mechanisms of such alterations remain unclear. Here, we investigate if BBB integrity is compromised in 22q11.2 delet...
Article
Treatments that target single mediators of sepsis have failed to reduce its high mortality rate. Here we developed multifunctional tannic acid-Zn²⁺-gentamicin nanoparticles (TA-Zn-Gen NPs) that target multiple mediators of sepsis to improve sepsis treatment. TA-Zn-Gen NPs with lower gentamicin content possessed net negative surface charge but still...
Preprint
Recent advances in therapeutic modulation of human microbiota have driven new efforts to engineer living microbial medicines using synthetic biology. However, a long-standing challenge for live bacterial therapies is balancing the high dose required to achieve robust efficacy with the potential for sepsis. Here, we developed a genetically encoded m...
Article
Design of micro- or nanocarriers for drug delivery has primarily been focused on properties such as hydrophobicity, biodegradability, size, shape, surface charge, and toxicity, so that they can achieve optimal delivery with respect to drug loading, release kinetics, biodistribution, cellular uptake, and biocompatibility. Incorporation of stimulus-s...
Preprint
Full-text available
The impact of long-term opioid exposure on the embryonic brain is crucial to healthcare due to the surging number of pregnant mothers with an opioid dependency. Current studies on the neuronal effects are limited due to human brain inaccessibility and cross-species differences among animal models. Here, we report a model to assess cell-type specifi...
Article
Janus metallic mesoporous silica nanoparticles (JMMSNs) possess biphasic geometries of distinct compositions or anisotropic structures that provide unique optical, magnetic, thermal, and electric properties for combined diagnosis and therapy in a potentially synergistic and stimuli-responsive manner. Here, we review the recent progress in the ratio...
Article
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Leukemia stem cells (LSCs) sustain the disease and contribute to relapse in acute myeloid leukemia (AML). Therapies that ablate LSCs may increase the chance of eliminating this cancer in patients. To this end, we used a bioreducible lipidoid-encapsulated Cas9/single guide RNA (sgRNA) ribonucleoprotein [lipidoid nanoparticle (LNP)–Cas9 RNP] to targe...
Article
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Silver nanoclusters (AgNCs) have outstanding physicochemical characteristics, including the ability to interact with proteins and DNA. Given the growing number of diagnostic and therapeutic applications of AgNCs, we evaluated the impact of AgNCs on DNA replication and DNA damage response in cell-free extracts prepared from unfertilized Xenopus laev...
Article
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Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicit...
Article
The radiotherapy enhancement effect of numerous nanosensitizers is based on the excessive production of reactive oxygen species (ROS), and only a few systematic reviews have focused on the key strategy in nanosensitizer-mediated radiotherapy. To clarify the mechanism underlying this effect, it is necessary to understand the role of ROS in radiosens...
Article
Circulating cell-free DNA (cfDNA) released by damaged cells causes inflammation and has been associated with the progression of sepsis. One proposed strategy to treat sepsis is to scavenge this inflammatory circulating cfDNA. Here, we develop a cfDNA-scavenging nanoparticle (NP) that consists of cationic polyethylenimine (PEI) of different molecula...
Article
Atherosclerosis begins with the accumulation of cholesterol‐carrying lipoproteins on blood vessel walls and progresses to endothelial cell dysfunction, monocyte adhesion, and foam cell formation. Endothelialized tissue‐engineered blood vessels (TEBVs) have previously been fabricated to recapitulate artery functionalities, including vasoconstriction...
Article
Full-text available
The COVID-19 pandemic has aggravated a preexisting epidemic: the opioid crisis. Much literature has shown that the circumstances imposed by COVID-19, such as social distancing regulations, medical and financial instability, and increased mental health issues, have been detrimental to those with opioid use disorder (OUD). In addition, unexpected neu...
Preprint
Full-text available
Periodontitis is a common type of inflammatory bone loss and is a risk factor for systemic diseases. The pathogenesis of periodontitis relies on inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. Here we demonstrate that cell-free DNA (cfDNA) is correlated with periodontitis in patient sampl...
Article
Full-text available
Chemotherapy causes off‐target toxicity and is often ineffective against solid tumors. Targeted and on‐demand release of chemotherapeutics remains a challenge. Here, cancer‐cell‐membrane‐coated mesoporous organosilica nanoparticles (MONs) containing X‐ray‐ and reactive oxygen species (ROS)‐responsive diselenide bonds for controlled release of doxor...
Article
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In article number 2004385, Dan Shao, Kam W. Leong, Wen‐fei Dong, and co‐workers present cancer‐cell‐membrane‐coated mesoporous organosilica nanoparticles for radiation‐responsive drug delivery and cancer chemo‐immunotherapy. Under low‐dose X‐ray radiation, such biomimetic nanotherapeutics exhibit degradation‐controlled drug release and induced stro...
Article
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Light is a particularly appealing tool for on‐demand drug delivery due to its noninvasive nature, ease of application, and exquisite temporal and spatial control. Great progress is achieved in the development of novel light‐driven drug delivery strategies with both breadth and depth. Light‐controlled drug delivery platforms can be generally categor...
Article
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Recent advances in CRISPR present attractive genome‐editing toolsets for therapeutic strategies at the genetic level. Here, a liposome‐coated mesoporous silica nanoparticle (lipoMSN) is reported as an effective CRISPR delivery system for multiplex gene‐editing in the liver. The MSN provides efficient loading of Cas9 plasmid as well as Cas9 protein/...
Article
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Drug screening in oncology, especially for triple-negative breast cancer (TNBC), has high demand but remains unsatisfactory. Currently available models are either nonrepresentative of the complex tumor microenvironment or only suitable for low throughput screening, resulting in a low-yield success for drug development. To tackle these issues, the L...
Article
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Cancer immunotherapy using cancer vaccines has shown great potential in the prevention and treatment of cancer. Here, we report an implantable autologous blood clot scaffold for enhanced cancer vaccination. It comprises a gel-like fibrin network formed by coagulation of blood to trap a large number of red blood cells. Upon implantation, the cross-l...
Article
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To reduce excessive scarring in wound healing, electrospun nanofibrous meshes, composed of haloarchaea-produced biodegradable elastomer poly(3-hydroxybutyrate- co-3-hydroxyvalerate) (PHBV), are fabricated for use as a wound dressing. Three PHBV polymers with different 3HV content are used to prepare either solution-cast films or electrospun nanofib...
Article
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Controlled release of CRISPR-Cas9 ribonucleoprotein (RNP) and codelivery with other drugs remain a challenge. We demonstrate controlled release of CRISPR-Cas9 RNP and codelivery with antitumor photosensitizer chlorin e6 (Ce6) using near-infrared (NIR)– and reducing agent–responsive nanoparticles in a mouse tumor model. Nitrilotriacetic acid–decorat...
Article
Cartilage defect is difficult to heal due to its avascular properties. Implantation of mesenchymal stem cell is one of the most promising approach for regenerating cartilage defects. Here we prepared polymeric nanofibrils decorated with cartilage-derived decellularized extracellular matrix (dECM) as a chondroinductive scaffold material for cartilag...
Article
Full-text available
Severe sepsis represents a common, expensive, and deadly health care issue with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis would help develop new therapeutic strategies against severe sepsis. In this study, we identified the crucial role of cell-free DNA (cfDNA) in the regulation of the Toll...
Article
Full-text available
Elevated cell-free DNA (cfDNA) levels in the plasma and synovial fluid of rheumatoid arthritis (RA) patients are proposed to be pathologically relevant. However, direct evidence to support this perception is lacking, and molecular feature of the cfDNA molecules with assumed pathological function is not well characterized. Here, we confirm remarkabl...
Article
Radiation dosimeters are critical for accurately assessing the levels of radiation exposure of tumor sites and surrounding tissues and for optimizing therapeutic interventions as well as for monitoring environmental exposure. To fill the need for a simple, user-friendly and inexpensive dosimeter, we designed an innovative colorimetric nanosensor-ba...
Article
Salmon calcitonin (sCT) is a potent calcium-regulating peptide hormone and widely applied for the treatment of some bone diseases clinically. However, the therapeutic usefulness of sCT is hindered by the frequent injection required owing to its short plasma half-life and therapeutic need for high dose. Oral delivery is a popular modality of adminis...
Article
Full-text available
In critical limb ischemia (CLI), overproduction of reactive oxygen species (ROS) and impairment of neovascularization contribute to muscle damage and limb loss. Cerium oxide nanoparticles (CNP, or ‘nanoceria’) possess oxygen-modulating properties which have shown therapeutic utility in various disease models. Here we show that CNP exhibit pro-angio...
Article
Liraglutide is a GLP-1 receptor agonist recently approved for Type-II diabetes (T2D) treatment with superior hypoglycemic effect while also improving cardiovascular function for the patients. However, its application has been limited by its short half-life (~13 h), which requires daily injections to maintain effective drug concentrations in blood,...