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  • I am a researcher and an entrepreneur in the science and engineering of biomedicine and healthcare. In 2022, I obtain... moreedit
Background: Multi-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community. However, low accumulation at the tumor sites and quick immune clearance of the... more
Background: Multi-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community. However, low accumulation at the tumor sites and quick immune clearance of the anti-tumor agents are still insurmountable challenges. Hypothetically, cancer cell membrane (CCM) can homologously target the tumor whereas multi-modal therapy can complement the disadvantages of singular therapies. Meanwhile, moderate hyperthermia induced by photothermal therapy can boost the cellular uptake of therapeutic agents by cancer cells. Results: CCM-cloaked indocyanine green (ICG)-incorporated and abraxane (PTX-BSA)-loaded layered double hydroxide (LDH) nanosheets (LIPC NSs) were fabricated for target efficient photo-chemotherapy of colorectal carcinoma (CRC). The CCM-cloaked LDH delivery system showed efficient homologous targeting and cytotoxicity, which was further enhanced under laser irradiation to synergize CRC apoptosis. On the other hand, CCM-cloaking remarkably reduced the uptake of LDH NSs by HEK 293T cells and macrophages, implying mitigation of the side effects and the immune clearance, respectively. In vivo data further exhibited that LIPC NSs enhanced the drug accumulation in tumor tissues and significantly retarded tumor progression under laser irradiation at very low therapeutic doses (1.2 and 0.6 mg/kg of ICG and PTX-BSA), without observed side effects on other organs. Conclusions: This research has demonstrated that targeting delivery efficiency and immune-escaping ability of LIPC NSs are tremendously enhanced by CCM cloaking for efficient tumor accumulation and in situ generated hyperthermia boosts the uptake of LIPC NSs by cancer cells, a potential effective way to improve the multi-modal cancer therapy.
A simple label-free method for the detection of Pb2+ ions with high selectivity and sensitivity has been developed by using random double-strand DNA-templated formation of copper nanoparticles as novel fluorescence probes in aqueous... more
A simple label-free method for the detection of Pb2+ ions with high selectivity and sensitivity has been developed by using random double-strand DNA-templated formation of copper nanoparticles as novel fluorescence probes in aqueous solution.
In this work, we describe a simple colorimetric method to detect DNA methylation. Adenomatous polyposis coli (APC) with a small CpG region containing methylated cytosine (methylated APC) was synthesized and tested. Methylated APC was... more
In this work, we describe a simple colorimetric method to detect DNA methylation. Adenomatous polyposis coli (APC) with a small CpG region containing methylated cytosine (methylated APC) was synthesized and tested. Methylated APC was first captured and enriched by anti-5-methylcytosine monoclonal antibody conjugated magnetic microspheres (MMPs). Then a probe partly complementary to the APC sequence was added, resulting in the formation of DNA duplexes. The microsphere-captured probe was then released by heat denaturation and added into unmodified gold nanoparticle (AuNP) solution. Colorimetric detection was performed by salt-induced aggregation. The limit of detection is 80 fmol. Semi-quantitative analysis was done with a UV/Vis spectrophotometer by recording the absorbance of AuNP solution at 520 nm. Thus, this method provides a simple, rapid and quantitative tool for DNA methylation detection.
A simple and rapid method for the detection of S2- anions with high selectivity and sensitivity has been developed by using random double-strand DNA-templated formation of copper nanoparticles as novel fluorescence probes in aqueous... more
A simple and rapid method for the detection of S2- anions with high selectivity and sensitivity has been developed by using random double-strand DNA-templated formation of copper nanoparticles as novel fluorescence probes in aqueous solution.
A fast and reliable sensing platform has been developed for the detection of mycotoxin ochratoxin A (OTA) based on a target-induced structure-switching signaling aptamer. In the absence of target, a fluorescein-labeled OTA aptamer... more
A fast and reliable sensing platform has been developed for the detection of mycotoxin ochratoxin A (OTA) based on a target-induced structure-switching signaling aptamer. In the absence of target, a fluorescein-labeled OTA aptamer hybridizes to a complementary DNA strand containing a quencher moiety, bringing the fluorophore and the quencher into close proximity for highly efficient fluorescence quenching. Upon OTA addition, a conformational change in the aptamer releases the quencher-containing DNA strand, generating a strong concentration-dependent fluorescent signal. Using this technique, the entire detection and analysis process of OTA can be completed within 1 min. Under optimized assay conditions, a wide linear detection range (from 1 to 100 ng/mL) was achieved with a detection limit down to 0.8 ng/mL Additionally, the proposed assay system exhibited high selectivity for OTA against other mycotoxins (aflatoxin B-1 and zearalenone) and limited interference from the structural analog ochratoxin B. The biosensor was also applied to a non-contaminated corn material spiked with a dilution series of OTA, obtaining recoveries from 83% to 106%. Utilization of the proposed biosensor for quantitative determination of mycotoxins in food samples may provide significant improvements in quality control of food safety through a simple, rapid, and sensitive testing system for agricultural products monitoring.
A double-stranded DNA (dsDNA) mediated sandwich assay was developed for quantitative detection of transcription factors. The detection limit for human recombinant c-jun protein is 2.5 ng, and for c-jun protein the limit is as low as 0.625... more
A double-stranded DNA (dsDNA) mediated sandwich assay was developed for quantitative detection of transcription factors. The detection limit for human recombinant c-jun protein is 2.5 ng, and for c-jun protein the limit is as low as 0.625 mu g of cell lysate.
A lateral flow biosensor for detection of single nucleotide polymorphism based on circular strand displacement reaction (CSDPR) has been developed. Taking advantage of high fidelity of T4 DNA ligase, signal amplification by CSDPR, and the... more
A lateral flow biosensor for detection of single nucleotide polymorphism based on circular strand displacement reaction (CSDPR) has been developed. Taking advantage of high fidelity of T4 DNA ligase, signal amplification by CSDPR, and the optical properties of gold nanoparticles, this assay has reached a detection limit of 0.01 fM.
A lateral flow biosensor based on isothermal strand-displacement polymerase reaction and gold nanoparticles has been developed for the visual detection of nucleic acids with a detection limit of 0.01 fM.
A hairpin DNA probe mediated cascade signal amplification method was developed for visual and rapid DNA analysis with a detection limit of 100 aM. The implementation of tag/anti-tag DNA and gold nanoparticle reporters permits a universal... more
A hairpin DNA probe mediated cascade signal amplification method was developed for visual and rapid DNA analysis with a detection limit of 100 aM. The implementation of tag/anti-tag DNA and gold nanoparticle reporters permits a universal platform for multiplex genotyping without instrumentation.
An autonomous thymine rich DNA machine as an amplification unit was developed for the sensitive detection of mercury ions with high specificity. Combined with a lateral flow biosensor, the amplified signal of Hg2+ can be read out by the... more
An autonomous thymine rich DNA machine as an amplification unit was developed for the sensitive detection of mercury ions with high specificity. Combined with a lateral flow biosensor, the amplified signal of Hg2+ can be read out by the naked eye with a detection limit of 5 nM.
Tuberculosis is a major communicable disease. Its causative agent, Mycobacterium tuberculosis, becomes resistant to antibiotics by acquisition of point mutations in the chromosome. Multi-drug-resistant tuberculosis (MDR-TB) is an... more
Tuberculosis is a major communicable disease. Its causative agent, Mycobacterium tuberculosis, becomes resistant to antibiotics by acquisition of point mutations in the chromosome. Multi-drug-resistant tuberculosis (MDR-TB) is an increasing public health threat, and prompt detection of such strains is of critical importance. As rolling circle amplification of padlock probes can be used to robustly distinguish single-nucleotide variants, we combined this technique with a sensitive lateral flow nucleic acid biosensor to develop a rapid molecular diagnostic test for MDR-TB, A proof-of-concept test was established for detection of the most common mutations [rpoB 531 (TCG/TTG) and katG 315 (AGC/ACC)] causing MDR-TB and verification of loss of the respective wild type. The molecular diagnostic test produces visual signals corresponding to the respective genotypes on lateral flow strips in approximately 75 min. By detecting only two mutations, the test can detect about 60% of all MDR-TB cases. The padlock probe-lateral flow (PLP-LF) test is the first of its kind and can ideally be performed at resource-limited clinical laboratories. Rapid information about the drug-susceptibility pattern can assist clinicians to choose suitable treatment regimens and take appropriate infection control actions rather than prescribing empirical treatment, thereby helping to control the spread of MDR-TB in the community.
Spexin is a novel hormone involved in obesity and diabetes while its biofunctional significance in lipid metabolism is still to be comprehended. Global metabolomic analysis in the present study revealed multiple metabolic pathways altered... more
Spexin is a novel hormone involved in obesity and diabetes while its biofunctional significance in lipid metabolism is still to be comprehended. Global metabolomic analysis in the present study revealed multiple metabolic pathways altered by spexin intraperitoneal (i.p.) injection in rat serum, which are highlighted by the changes in several bile acid metabolites. In rats, spexin (300 mu g/kg) could dramatically reduce hepatic and circulating total bile acids (TBA) level compared with the controls. Correspondingly, treatment with spexin by i.p. injection for 28 days led to significant decrease in serum TBA and gallbladder weight in C57BL/6J mice. In enterohepatic circulation system, spexin effectively reduced TBA levels in mouse liver and gallbladder but not the intestine. Hepatic cholesterol 7 alpha-hydroxylase 1 (CYP7A1) expression, unsurprisingly, was suppressed by spexin injection. Both GALR2 and GALR3 antagonists reversed the inhibitory effects of spexin on concentrations of serum TBA and 7 alpha-hydroxy-4-cholesten-3-one (C4), and hepatic CYP7A1 expression. Finally, negative correlations were observed between serum spexin and total cholesterol (TC), total bile acid (TBA), tauro-chenodeoxycholate (TCDCA), as well as glycochenodeoxycholate (GCDCA) in 91 healthy volunteers. These findings illuminate the intrinsic importance of spexin in the regulation of bile acid synthesis and metabolism.
Cancer vaccines have attracted increasing attention for their application in tumor immunotherapy. DNA vaccines are one of them that have been proven very promising with the advantages of safety, rapid design, and low cost. However, the... more
Cancer vaccines have attracted increasing attention for their application in tumor immunotherapy. DNA vaccines are one of them that have been proven very promising with the advantages of safety, rapid design, and low cost. However, the low stability, ineffective cell internalization, and low immunostimulation hinder their wide application. Thus, developing targeted and safe systems to effectively deliver DNA vaccines becomes a vital step. In this study, we report the development of mannose- and bisphosphonate (BP)modified calcium phosphate (CP) nanoparticles (NPs) as efficient vaccine delivery vehicles by targeting C-type lectin receptors (CLRs) on antigen-presenting cells (APCs). Using a model antigen ovalbumin (OVA)-encoded plasmid DNA (pOVA) as a model vaccine, we demonstrate that mannose-modified and BP-stabilized CP (MBCP) nanoparticles are mono-dispersed for enhanced uptake by APCs and subsequently induce OVA antigen presentation and immunostimulation. Mice immunized with MBCP-pOVA nanovaccines show a significantly stronger anti-OVA antibody response with a quicker IgG1 and IgG2a antibody production than unmodified NPs. Moreover, MBCP-pOVA immunization significantly inhibits the growth of OVA-expressing E.G7 tumor cells in C57BL/6J mice. Our data collectively suggest that the modifications to enhance the stability and targeting ability of MBCP NPs are essential for effective delivery of DNA vaccines and promote robust anti-tumor immunity.
Immunotherapy has made great progress in recent years while most cancer patients cannot benefit from it. Photochemotherapy combination strategy holds great promise for developing novel immunotherapy for the patients bearing... more
Immunotherapy has made great progress in recent years while most cancer patients cannot benefit from it. Photochemotherapy combination strategy holds great promise for developing novel immunotherapy for the patients bearing immunosuppressive tumors such as colon cancer. In this research, a novel core/shell-structured polydopamine (PDA)-based nanoplatform is constructed to load two Food and Drug Administration (FDA)-approved cytotoxic drugs, i.e. immunostimulatory doxorubicin (Dox) and immunomodulatory curcumin (Cur) to achieve immunostimulatory photochemotherapy of primary colon tumors upon 808 nm near infrared (NIR) irradiation (1 W/cm(2) for 5 min) and subsequent prevention of rechallenged distant colon tumors. The experimental data have shown that PDA-mediated photothermal therapy (PTT) synergized two therapeutic drugs in inducing colon cancer cell death and very efficiently inhibited the primary tumor growth (by similar to 92%) at very low doses of therapeutics (0.25, 5, and 30 mg/kg of Dox, Cur, and PDA, respectively). More significantly, the combined photochemotherapy promoted strong adaptive antitumor immune responses and successfully prevented tumorigenesis in the setting of tumor rechallenge model. Our research has thus demonstrated the promising efficacy of this photochemotherapeutic nanoformulation for colon cancer treatment and provided a way to improve immunostimulatory effects of conventional chemotherapeutic drugs.
Tripeptide glutathione (GSH) is an abundant and ubiquitous metabolite in living organisms and plays critical roles in various cellular processes. In this work{,} we report the development of a new nanoprobe (MnO2–PEI–FITC) for GSH... more
Tripeptide glutathione (GSH) is an abundant and ubiquitous metabolite in living organisms and plays critical roles in various cellular processes. In this work{,} we report the development of a new nanoprobe (MnO2–PEI–FITC) for GSH detection and imaging by exploiting the response mechanism of specific GSH-triggered reduction of manganese dioxide (MnO2) nanosheets. The MnO2–PEI–FITC nanoprobe was developed by coating negatively charged MnO2 nanosheets with a positively charged polyethylenimine (PEI) polymer{,} followed by coupling with fluorescein isothiocyanate (FITC) through a thiourea linkage. The MnO2–PEI–FITC nanoprobe showed weak fluorescence due to the quenching of FITC emission absorption by MnO2{,} while the emission of FITC at 518 nm was observed in the presence of GSH. The MnO2–PEI–FITC nanoprobe is featured with a rapid response to GSH (<12 min){,} high sensitivity (detection limit{,} 164 nM) and selectivity. The application of this nanoprobe for GSH imaging in fresh yeast cells and onion inner-layer epidermal tissues was then successfully demonstrated. This work thus provides a new nanoprobe for GSH detection and imaging in biological samples.
Breast cancer is the most common one in women worldwide and doxorubicin (Dox) is one of the most commonly used and effective drugs for breast cancer treatment. Unfortunately, Dox-based chemotherapy faces irreversible cardiotoxicity and... more
Breast cancer is the most common one in women worldwide and doxorubicin (Dox) is one of the most commonly used and effective drugs for breast cancer treatment. Unfortunately, Dox-based chemotherapy faces irreversible cardiotoxicity and unsatisfactory therapy efficiency. It is desirable to devise Dox nanoformulations with less adverse effects and greater therapeutic efficacy for this cancer treatment. In this work, a multifunctional calcium phosphate nanoformulation (ICG-Dox/DNA@CaP) was developed by co-loading Dox/DNA complexes and indocyanine green (ICG) molecules for photothermal therapy (PTT)enhanced chemotherapy. In this nanocomposite, using DNA as Dox carrier facilitated Dox loading into the CaP matrix, and significantly reduced Dox leakage as well as cytotoxicity in comparison with that of free Dox in physiological medium (pH 7.4). In specific, ICG-Dox/DNA@CaP only released Dox in a weakly acidic nuclease-containing environment, such as tumor microenvironment and endosome/lysosome. Moreover, Dox/DNA complexes exhibited synergistic interactions with ICG-based photothermal effect on tumor cell apoptosis in this ICG-Dox/DNA@CaP nanocomposite. This work has demonstrated a new strategy to combine FDA-approved therapeutics (Dox and ICG) in CaP-based nanomaterials for reduced cytotoxicity and enhanced therapeutic effect, and provided a new way to engineer CaP carriers as multifunctional delivery systems for clinical anti-cancer therapy.
To overcome the severe side effects of cancer chemotherapy, it is vital to develop targeting chemotherapeutic delivery systems with the potent inhibition of tumour growth, angiogenesis, invasion and migration at low drug dosages. For this... more
To overcome the severe side effects of cancer chemotherapy, it is vital to develop targeting chemotherapeutic delivery systems with the potent inhibition of tumour growth, angiogenesis, invasion and migration at low drug dosages. For this purpose, we co-loaded a conventional antiworm drug, albendazole (ABZ), and a TOPK inhibitor, OTS964, into lipid-coated calcium phosphate (LCP) nanoparticles for skin cancer treatment. OTS- and ABZ-loaded LCP (OTS-ABZ-LCP) showed a synergistic cytotoxicity against skin cancer cells through their specific cancerous pathways, without obvious toxicity to healthy cell lines. Moreover, dual-targeting the programmed death ligand-1 (PD-L1) and folate receptor overexpressed on the surface of skin cancer cells completely suppressed the skin tumour growth at low doses of ABZ and OTS. In summary, ABZ and OTS co-loaded dual-targeting LCP NPs represent a promising platform with high potentials against complicated cancers where PD-L1/FA dual targeting appears as an effective approach for efficient and selective cancer therapy.
Direct hypoxia alleviation and lactate depletion in the tumor microenvironment (TME) are promising for effective cancer therapy but still very challenging. To address this challenge, the current research directly reshapes the TME for... more
Direct hypoxia alleviation and lactate depletion in the tumor microenvironment (TME) are promising for effective cancer therapy but still very challenging. To address this challenge, the current research directly reshapes the TME for inhibiting tumor growth and activating the antitumor immunity using a drug-free nanozyme. Herein, the acid-sensitive nanozymes were constructed based on peroxidized layered double hydroxide nanoparticles for O2 self-supply and self-boosted lactate depletion. The coloading of partially cross-linked catalase and lactate oxidase enabled the acid-sensitive nanozymes to promote three reactions, that is, (1) H2O2 generation from MgO2 hydrolysis (30% at pH 7.4 vs 63% at pH 6.0 in 8 h); (2) O-2 generation from H2O2 (12% at pH 7.4 vs 21% at pH 6.0 in 2 h); and (3) lactate depletion by in situ generated O2 (50% under hypoxia vs 75% under normoxia in 24 h in vitro) in parallel or tandem. These promoted reactions together efficiently induced colon cancer cell apoptosis under the hypoxic conditions, significantly inhibited tumor growth (>95%), and suppressed distant tumor growth upon seven administrations in every 3 days and moreover transformed the immunosuppressive tumor into "hot" one in the colon tumor-bearing mouse model. This is the first example for a nanozyme that supplies sufficient O-2 for hypoxia relief and lactate depletion, thus providing a new insight into drug-free nanomaterial-mediated TME-targeted cancer therapy.
Metallodrug platinum compounds are indispensable components in the current standard combination for colorectal cancer treatment yet with severe additional adverse effects compromising the clinical outcomes. Having tumor microenvironment... more
Metallodrug platinum compounds are indispensable components in the current standard combination for colorectal cancer treatment yet with severe additional adverse effects compromising the clinical outcomes. Having tumor microenvironment modulation and immunostimulatory effect, bio-compatible manganese (Mn) materials hold great promise for developing alternate metallodrug combination treatments. In this research, a novel MnO2-shelled nanoplatform was constructed to load two FDA-approved anti-tumor drugs, i.e., immunomodulatory curcumin (Cur) and immunostimulatory doxorubicin (Dox) to achieve enhanced dual-chemotherapy of primary tumors and remarkable inhibition of distant colorectal tumors. The experimental results have shown that MnO2 efficiently enhanced Dox/Cur chemotherapy with significant primary tumor inhibition (81%) at very low dosages (5.0 and 1.0 mg/kg of Cur and Dox, respectively). Furthermore, the MnO2-assisted Dox/Cur chemotherapy promoted strong tumoricidal adaptive immune responses and overwhelmingly inhibited tumorigenesis in the tumor rechallenge experiment. This work has thus demonstrated the promising efficacy of the Mn/Dox/Cur nano-formulation and provided a novel way to improve immunostimulation of conventional chemotherapeutics using active metal oxide nanomaterials for colorectal cancer treatment.
Pleiotropic drug nanoformulation promises the enhanced efficacy of nanomedicines on the market. In this study, it is demonstrated that polydopamine (PDA)-based drug encapsulation is a potential strategy for such nanoformulation, yet its... more
Pleiotropic drug nanoformulation promises the enhanced efficacy of nanomedicines on the market. In this study, it is demonstrated that polydopamine (PDA)-based drug encapsulation is a potential strategy for such nanoformulation, yet its mechanism remains poorly investigated. This study elucidates the mechanism of PDA-encapsulated Curnanoformulations (CP NPs) using hydrophobic curcumin (Cur) as a model drug via local dopamine (DA) polymerization on self-assembled Cur NPs. The formation of PDA-based drug nanoformulations with the core–shell structure is comprehensively investigated by controlling the key synthetic parameters, deepening the understanding of DA polymerization in the context of drugs. An intriguing morphology evolution is proposed to be the key event in the formation of CP NPs, attributing to the Cur diffusion from the core to the shell of CP NPs. Moreover, the morphological data can be used to guide the optimization of the PDA-based nanoformulation. In addition, the verification of soluble DA polymers in CP NPs hints at the heterogeneous nature of the excipient (i.e., PDA) of CP NPs, providing a cautionary view on the long-term safety of PDA-formulated drugs. In sum, this study would enable the pharmaceutical development of PDA-encapsulated Cur nanomedicines and generalize the PDA-based nanoformulation approach for a wider range of hydrophobic drugs.
Immuno-stimulative effect of chemotherapy (ISECT) is recognized as a potential alternative to conventional immunotherapies, however, the clinical application is constrained by its inefficiency. Metronomic chemotherapy, though designed to... more
Immuno-stimulative effect of chemotherapy (ISECT) is recognized as a potential alternative to conventional immunotherapies, however, the clinical application is constrained by its inefficiency. Metronomic chemotherapy, though designed to overcome the limitation, offers inconsistent results, with effectiveness varying based on cancer types, stages, and patient-specific factors. In parallel, a wealth of preclinical nanomaterials holds considerable promise for ISECT improvement by modulating the cancer-immunity cycle. In the area of biomedical nanomaterials, current literature reviews mainly concentrate on a specific category of nanomaterials and nanotechnological perspectives, while two essential issues are still lacking, i.e., a comprehensive analysis addressing the causes for ISECT inefficiency and a thorough summary elaborating the nanomaterials for ISECT improvement. This review thus aims to fill these gaps and catalyze further development in this field. For the first time, this review comprehensively discusses the causes of ISECT inefficiency. It then meticulously categorizes six types of nanomaterials for improving ISECT. Subsequently, practical strategies are further proposed for addressing inefficient ISECT, along with a detailed discussion on exemplary nanomedicines. Finally, this review provides insights into the challenges and perspectives for improving chemo-immunotherapy by innovations in nanomaterials.
Chaenomeles speciosa (Sweet) Nakai fruit is a good source of phenolics with many health benefits. In this work, the enrichment of C. speciosa fruit total phenolics (CSFTP) using macroporous resins was studied. NKA-Ⅱ resin was selected for... more
Chaenomeles speciosa (Sweet) Nakai fruit is a good source of phenolics with many health benefits. In this work, the enrichment of C. speciosa fruit total phenolics (CSFTP) using macroporous resins was studied. NKA-Ⅱ resin was selected for enriching CSFTP due to its highest adsorption/desorption quantity. Adsorption characteristics of CSFTP on NKA-Ⅱ resin exhibited a good fit with the Langmuir isotherm model and pseudo-second order kinetics model. This adsorption was spontaneous, exothermic, and entropy-decreasing through a physisorption mechanism. The breakthrough-elution curves were studied to optimize CSFTP enrichment conditions. One-step enrichment increased CSFTP content in the extracts from 26.51 % to 78.63 %, with a recovery of 81.03 %. A UPLC-QqQ-MS/MS method in multiple reaction monitoring (MRM) mode was established and validated for the simultaneous quantification of seven phenolic compounds. This study demonstrates the feasibility of industrial enrichment of CSFTP using NKA-Ⅱ resin and proposes a reliable method for quality control of CSFTP-rich products.