TMU EYC Lab
Research Features
Wireless, self‑powered phototrophic algaerobot‑infused nanotherapeutic hydrogels for enhanced diabetic wound healing
Chemical Engineering Journal, 163469, July 2025
Diabetic wounds present a significant clinical challenge due to impaired immunity, hypoxia, poor neovascularization, and chronic inflammation, often resulting in severe complications such as amputation. Conventional therapies, including hyperbaric oxygen, antioxidants, and electrical stimulation, face limitations in delivering sustained and safe oxygen, hydrogen, and electrical stimulation to the wound site. This study introduces a groundbreaking approach by integrating phototrophic algae robots (AR) into a methylcellulose (MC) hydrogel, combined with platelet-derived extracellular vesicles (pEVs) and conductive glycol chitosan-polypyrrole nanoparticles (GCS-PPy NPs), forming a multifunctional composite system (MC-pEV-AR-GCS-PPy NPs).
Nano-orchestrated magnetotactic-like navigation for electromagnetic theranostics and immune enhancement via photoautotrophic oxygenation, mild hyperthermia, and ferroptosis
Journal of Nanobiotechnology, 23 (1), 442 , Jun 2025
Overcoming the hypoxic tumor microenvironment (TME) and immune suppression remains a significant challenge in solid bladder tumor therapies. This study introduces a translational system of nano-orchestrated magnetotactic-like system, integrating photosynthetic oxygenation, remote hyperthermia, and ferroptosis to achieve comprehensive tumor eradication and immune activation. The developed system, composed of electromagnetic-responsive iron oxide nanoparticles (IO NPs) encapsulated within a glycol chitosan (GCS) matrix and coated onto Chlorella (CHL; CHL-GCS-IO NPs), exhibited versatility for precise magnetic targeting, photothermal-hypertehrmia and photosynthesis-driven oxygen generation under light irradiation. The CHL enhanced oxygen production by continuously alleviating hypoxia, boosting both electromagnetic therapeutic efficacies and ferroptosis-induced tumor cell death. Moreover, the multimodal CHL-GCS-IO NPs reprogrammed the TME, facilitating immune activation by promoting macrophage polarization towards the proinflammatory M1 phenotype, engaging cytotoxic T cells and natural killer cells, programmed death ligand 1 (PD-L1) downregulation, and driving dendritic cell reprogramming towards improved antigen presentation.
Intranasal delivery of epigallocatechin gallate-laden platelet extracellular vesicles for mitigating retinal glaucoma
Journal of Controlled Release, 381, 13596 , May 2025
Glaucoma is a serious cause of permanent blindness worldwide, mainly caused by inflammation and degeneration of the optic nerve. However, current treatments using systemically administered drugs have limited effectiveness due to various biological barriers that prevent their biodistribution in the eye. To overcome these challenges, we developed a new therapy that utilizes intranasal delivery to retinal lesions. In this therapy, we used platelet extracellular vesicles (pEVs) as carriers for epigallocatechin gallate (EGCG), which is known for its neuroprotective, anti-inflammatory, and immunomodulatory properties.
Hierarchically structured conductive hydrogels for electrically programmable drug delivery in a diabetic wound healing electronic patch Journal of Controlled Release, 113760, Apr 2025
Smart wound dressings that integrate advanced drug delivery strategies and electrical stimulation (ES) represent a revolutionary approach for improving diabetic wound healing. However, limited drug loading efficiency and delayed reactivity to electrical inputs make it difficult to practically implement ES-controlled drug release in hydrogel-coated electrodes.
Enhanced scar mitigation via hyperbaric oxygen therapy and immune modulation using nanoparticle-orchestrated photosynthetic chlorella in polysaccharide hydrogels
Chemical Engineering Journal, 509, 160666, Apr 2025
Immunotherapy for fibroproliferative disorders shows great promise but is often limited by insufficient induction of immune responses. In this study, Chlorella (CHL) stimulates the immune response by activating photosynthetic and oxygen signaling pathways in macrophages, leading to the production of immunostimulatory factors.
Alleviating rheumatoid arthritis with a photo-pharmacotherapeutic glycan-integrated nanogel complex for advanced percutaneous delivery
Journal of Nanobiotechnology 22 (646), Oct 2024
The prospective of percutaneous drug delivery (PDD) mechanisms to address the limitations of oral and injectable treatment for rheumatoid arthritis (RA) is increasing. These limitations encompass inadequate compliance among patients and acute gastrointestinal side effects. However, the skin’s intrinsic layer can frequently hinder the percutaneous dispersion of RA medications, thus mitigating the efficiency of drug delivery. To circumvent this constraint, we developed a strontium ranelate (SrR)-loaded alginate (ALG) phototherapeutic hydrogel to assess its effectiveness in combating RA.
Platelet Extracellular Vesicles Loaded Gelatine Hydrogels for Wound Care
Advanced healthcare materials, 14(1), 2401914, Oct 2024
Platelet extracellular vesicles (pEVs) isolated from clinical-grade human platelet concentrates are attracting attention as a promising agent for wound healing therapies. Although pEVs have shown potential for skin regeneration, their incorporation into wound bandages has remained limitedly explored. Herein, gelatine-based hydrogel (PAH-G) foams for pEVs loading and release are formulated by crosslinking gelatine with poly(allylamine) hydrochloride (PAH) in the presence of glutaraldehyde and sodium bicarbonate. The optimized PAH-G hydrogel foam, PAH0.24G37, displayed an elastic modulus G’ = 8.5 kPa at 37 °C and retained a rubbery state at elevated temperatures. The excellent swelling properties of PAH0.24G37 allowed to easily absorb pEVs at high concentration (1 × 1011 particles mL−1). The therapeutic effect of pEVs was evaluated in vivo on a chronic wound rat model. These studies demonstrated full wound closure after 14 days upon treatment with PAH0.24G37@pEVs.
Phototactic/Photosynthetic/Magnetic-Powered Chlamydomonas Reinhardtii-Metal-Organic Frameworks Micro/Nanomotors for Intelligent Thrombolytic Management and Ischemia Alleviation
Advanced healthcare materials 13 (29), 2401383, Aug 2024
Thrombosis presents a critical health threat globally, with high mortality and incidence rates. Clinical treatment faces challenges such as low thrombolytic agent bioavailability, thrombosis recurrence, ischemic hypoxia damage, and neural degeneration. This study developed biocompatible Chlamydomonas Reinhardtii micromotors (CHL) with photo/magnetic capabilities to address these needs. These CHL micromotors, equipped with phototaxis and photosynthesis abilities, offer promising solutions. A core aspect of this innovation involves incorporating polysaccharides (glycol chitosan (GCS) and fucoidan (F)) into ferric Metal-organic frameworks (MOFs), loaded with urokinase (UK), and subsequently self-assembled onto the multimodal CHL, forming a core-shell microstructure (CHL@GCS/F-UK-MOF). Under light-navigation, CHL@GCS/F-UK-MOF is shown to penetrate thrombi, enhancing thrombolytic biodistribution. Combining CHL@GCS/F-UK-MOF with the magnetic hyperthermia technique achieves stimuli-responsive multiple-release, accelerating thrombolysis and rapidly restoring blocked blood vessels. Moreover, this approach attenuates thrombi-induced ischemic hypoxia disorder and tissue damage.
Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair
Carbohydrate Polymers 339, 122174, Sept 2024
Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects.
Light-Driven Green-Fabricated Artificial Intelligence-Enabled Micro/Nanorobots for Multimodal Phototherapeutic Management of Bladder Cancer
Advanced healthcare materials, 13(32), 2402864, Sept 2024
Combination therapy based on precise phototherapies combined with immune modulation provides successful antitumor effects. In this study, a combination therapy is designed based on phototactic, photosynthetic, and phototherapeutic Chlamydomonas Reinhardtii (CHL)-glycol chitosan (GCS)-polypyrrole (PPy) nanoparticle (NP)-enhanced immunity combined with the tumor microenvironment turnover of cytotoxic T cells and M1/M2 macrophages, which is based on photothermal GCS-PPy NPs decorated onto the phototactic and photosynthetic CHL. Phototherapy based on CHL-GCS-PPy NPs alleviates hypoxia and modulates the tumor immune microenvironment, which induces tumor cell death. In particular, the precise antitumor immune response and potent immune memory induced by combining self-navigated phototherapies significantly alleviate the progression of bladder cancer in C57BL/6 mice and effectively inhibit bladder tumor growth. Furthermore, they also potentially prevent tumor recurrence, which provides a promising therapeutic strategy for clinical tumor therapy.
Spermatozoon-propelled microcellular submarines combining innate magnetic hyperthermia with derived nanotherapies for thrombolysis and ischemia mitigation
Journal of Nanobiotechnology 22 (646), Aug 2024
Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was “switched-on” by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia.
Plasma-Derived Nanoclusters for Site-Specific Multimodality Photo/Magnetic Thrombus Theranostics
Advanced healthcare materials 12 (28), 2301504, Nov 2023
Traditional thrombolytic therapeutics for vascular blockage are affected by their limited penetration into thrombi, associated off-target side effects, and low bioavailability, leading to insufficient thrombolytic efficacy. It is hypothesized that these limitations can be overcome by the precisely controlled and targeted delivery of thrombolytic therapeutics. A theranostic platform is developed that is biocompatible, fluorescent, magnetic, and well-characterized, with multiple targeting modes. This multimodal theranostic system can be remotely visualized and magnetically guided toward thrombi, noninvasively irradiated by near-infrared (NIR) phototherapies, and remotely activated by actuated magnets for additional mechanical therapy. Magnetic guidance can also improve the penetration of nanomedicines into thrombi. In a mouse model of thrombosis, the thrombosis residues are reduced by ≈80% and with no risk of side effects or of secondary embolization. This strategy not only enables the progression of thrombolysis but also accelerates the lysis rate, thereby facilitating its prospective use in time-critical thrombolytic treatment.
Enhanced diabetic wound healing using platelet-derived extracellular vesicles and reduced graphene oxide in polymer-coordinated hydrogels
Journal of Nanobiotechnology 21 (1), 318, Sept 2023
Impaired wound healing is a significant complication of diabetes. Platelet-derived extracellular vesicles (pEVs), rich in growth factors and cytokines, show promise as a powerful biotherapy to modulate cellular proliferation, angiogenesis, immunomodulation, and inflammation. For practical home-based wound therapy, however, pEVs should be incorporated into wound bandages with careful attention to delivery strategies. In this work, a gelatin-alginate hydrogel (GelAlg) loaded with reduced graphene oxide (rGO) was fabricated, and its potential as a diabetic wound dressing was investigated. The GelAlg@rGO-pEV gel exhibited excellent mechanical stability and biocompatibility in vitro, with promising macrophage polarization and reactive oxygen species (ROS)-scavenging capability. In vitro cell migration experiments were complemented by in vivo investigations using a streptozotocin-induced diabetic rat wound model. When exposed to near-infrared light at 2 W cm− 2, the GelAlg@rGO-pEV hydrogel effectively decreased the expression of inflammatory biomarkers, regulated immune response, promoted angiogenesis, and enhanced diabetic wound healing. Interestingly, the GelAlg@rGO-pEV hydrogel also increased the expression of heat shock proteins involved in cellular protective pathways.
A Biomimicking and Multiarm Self-Indicating Nanoassembly for Site-Specific Photothermal-Potentiated Thrombolysis Assessed in Microfluidic and In Vivo Models
Advanced Healthcare Materials 12 (24), 2300682, Sept 2023
Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off-target hemorrhage. Integrating a thrombus-homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near-infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.
P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses
Journal of Nanobiotechnology 21 (1), 260, Aug 2023
Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery.
Plasma-treated nano-enabled multimodal coatings made of phototherapeutic molybdenum disulfide and fucoidan prevent catheter-associated urinary tract issues
Chemical Engineering Journal 468, 143749, Jul 2023
The primary barriers preventing the use of silicone-based catheters in medicine, especially for long-term indwelling, are bacterial-related illnesses, blood clotting, inflammation, and cell and tissue adhesion. To address the challenges related to the use of silicone-based catheters, this study presents a novel approach for developing a facile coating composed of anionic and amphiphilic fucoidan (Fu) and phototherapeutic molybdenum disulfide (MoS2) nanomicelles (Fu-MoS2 NMs) through oxygen plasma irradiation. The coating was consecutively applied to medical-grade silicone-based catheters. In this study, stable polymeric coatings were successfully prepared on previously used silicone rubber substrates through the formation of intermolecular bonds between active functional groups in Fu-MoS2 NMs and the side chains of residues on activated silicone interfaces.
IR-inspired visual display/response device fabricated using photothermal liquid crystals for medical and display applications
Chemical Engineering Journal 429, 132213, Feb 2022
Combined applications of composite materials are very important in today’s science, especially those of liquid crystal (LC) materials. Visualization of near-infrared (NIR) with zero power consumption using a combination of photothermal and LC materials is urgently needed. In this study, a device was constructed from thermosensitive cholesteric LC (CLC) and nano-level polypyrrole materials, and named a photothermal polypyrrole nano-pigment-integrated with CLC (PNCLC) display element. A change in the reflected light of the CLC display element was achieved by the photoabsorption-exothermic characteristics of polypyrrole, which absorbs NIR light to drive the photothermal performance. The temperature and color change caused by the absorption of NIR light resulted in the CLC display element automatically indicating a change in the NIR intensity.