Sha Liu

Bio: Sha Liu is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Materials science & Medicine. The author has an hindex of 11, co-authored 22 publications receiving 358 citations. Previous affiliations of Sha Liu include University of Architecture, Civil Engineering and Geodesy & University of Science and Technology of China.

Gold nanorod@silica-carbon dots as multifunctional phototheranostics for fluorescence and photoacoustic imaging-guided synergistic photodynamic/photothermal therapy.

Abstract: Phototheranostics, which is the application of light in the diagnostic imaging and therapy of cancer, has shown great promise for multimodal cancer imaging and effective therapy. Herein, we developed multifunctional gold nanorod@silica-carbon dots (GNR@SiO2-CDs) as a phototheranostic agent by incorporating carbon dots (CDs) with gold nanorods (GNRs), using SiO2 as a scaffold. In GNR@SiO2-CDs, the GNRs act as both photoacoustic (PA) imaging and photothermal therapy (PTT) agents, and the CDs serve as fluorescence (FL) imaging and photodynamic therapy (PDT) agents. The introduction of SiO2 not only improves the chemical stability of the GNRs and CDs in the physiological environment but also prevents the absolute quenching of the fluorescence of the CDs by GNRs. These collective properties make GNR@SiO2-CDs a novel phototheranostic agent, in which high sensitivity and good spatial resolution of FL/PA imaging can be achieved to guide PDT/PTT treatments through i.v. administration. The combination of PDT and PTT proved to be more efficient in killing cancer cells compared to PDT or PTT alone under a low dose of laser irradiation (≤0.5 W cm−2). Furthermore, GNR@SiO2-CDs could be cleared out from the body of mice, indicating the low toxicity of this phototheranostic agent. Our work highlights the potential of using GNRs and CDs as novel phototheranostic agents for multifunctional cancer therapies.

Absorbable Thioether Grafted Hyaluronic Acid Nanofibrous Hydrogel for Synergistic Modulation of Inflammation Microenvironment to Accelerate Chronic Diabetic Wound Healing

Abstract: Current standard of care dressings are unsatisfactorily inefficacious for the treatment of chronic wounds. Chronic inflammation is the primary cause of the long-term incurable nature of chronic wounds. Herein, an absorbable nanofibrous hydrogel is developed for synergistic modulation of the inflammation microenvironment to accelerate chronic diabetic wound healing. The electrospun thioether grafted hyaluronic acid nanofibers (FHHA-S/Fe) are able to form a nanofibrous hydrogel in situ on the wound bed. This hydrogel degrades and is absorbed gradually within 3 days. The grafted thioethers on HHA can scavenge the reactive oxygen species quickly in the early inflammation phase to relieve the inflammation reactions. Additionally, the HHA itself is able to promote the transformation of the gathered M1 macrophages to the M2 phenotype, thus synergistically accelerating the wound healing phase transition from inflammation to proliferation and remodeling. On the chronic diabetic wound model, the average remaining wound area after FHHA-S/Fe treatment is much smaller than both that of FHHA/Fe without grafted thioethers and the control group, especially in the early wound healing stage. Therefore, this facile dressing strategy with intrinsic dual modulation mechanisms of the wound inflammation microenvironment may act as an effective and safe treatment strategy for chronic wound management.

Self-Assembled Carbon Dot Nanosphere: A Robust, Near-Infrared Light-Responsive, and Vein Injectable Photosensitizer.

Abstract: Self-assembly “activated” carbon dot photosensitizer: a robust, NIR-light responsive, and vein injectable carbon dot nanosphere (CDNS) photosensitizer with 1O2 quantum yield of 0.45 under 671 nm laser irradiation has been developed through self-assembly using individual CD as building units. This study develops the biomedical applications of CD, highlights the self-assembly for designing well-defined CD-based photosensitizers, and promotes future explorations of this CDNS photosensitizer in nanomedical and clinical applications.

Versatile Polymer Nanoparticles as Two-Photon-Triggered Photosensitizers for Simultaneous Cellular, Deep-Tissue Imaging, and Photodynamic Therapy.

Abstract: Clinical applications of current photodynamic therapy (PDT) photosensitizers (PSs) are often limited by their absorption in the UV-vis range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep-seated tumors. Alternatively, two-photon excited PS (TPE-PS) using NIR light triggered is one the most promising candidates for PDT improvement. Herein, multimodal polymer nanoparticles (PNPs) from polythiophene derivative as two-photon fluorescence imaging as well as two-photon-excited PDT agent are developed. The prepared PNPs exhibit excellent water dispersibility, high photostability and pH stability, strong fluorescence brightness, and low dark toxicity. More importantly, the PNPs also possess other outstanding features including: (1) the high 1 O2 quantum yield; (2) the strong two-photon-induced fluorescence and efficient 1 O2 generation; (3) the specific accumulation in lysosomes of HeLa cells; and (4) the imaging detection depth up to 2100 µm in the mock tissue under two-photon. The multifunctional PNPs are promising candidates as TPE-PDT agent for simultaneous cellular, deep-tissue imaging, and highly efficient in vivo PDT of cancer.

Development of organic semiconducting materials for deep-tissue optical imaging, phototherapy and photoactivation

Abstract: Biophotonics as a highly interdisciplinary frontier often requires the assistance of optical agents to control the light pathways in cells, tissues and living organisms for specific biomedical applications. Organic semiconducting materials (OSMs) composed of π-conjugated building blocks as the optically active components have recently emerged as a promising category of biophotonic agents. OSMs possess common features including excellent optical properties, good photostability and biologically benign composition. This review summarizes the recent progress in the development of OSMs based on small-molecule fluorophores, aggregation-induced emission (AIE) dyes and semiconducting oligomer/polymer nanoparticles (SONs/SPNs) for advanced biophotonic applications. OSMs have been exploited as imaging agents to transduce biomolecular interactions into second near-infrared fluorescence, chemiluminescence, afterglow or photoacoustic signals, enabling deep-tissue ultrasensitive imaging of biological tissues, disease biomarkers and physiological indexes. By fine-tuning the molecular structures, OSMs can also convert light energy into cytotoxic free radicals or heat, allowing for effective cancer phototherapy. Due to their instant light response and efficient light-harvesting properties, precise regulation of biological activities using OSMs as remote transducers has been demonstrated for protein ion channels, gene transcription and protein activation. In addition to highlighting OSMs as a multifunctional platform for a wide range of biomedical applications, current challenges and perspectives of OSMs in biophotonics are discussed.

Photosensitizers for Photodynamic Therapy

Abstract: As an emerging clinical modality for cancer treatment, photodynamic therapy (PDT) takes advantage of the cytotoxic activity of reactive oxygen species (ROS) that are generated by light irradiating photosensitizers (PSs) in the presence of oxygen (O2 ). However, further advancements including tumor selectivity and ROS generation efficiency are still required. Substantial efforts are devoted to design and synthesize smart PSs with optimized properties for achieving a desirable therapeutic efficacy. This review summarizes the recent progress in developing intelligent PSs for efficient PDT, ranging from single molecules to delicate nanomaterials. The strategies to improve ROS generation through optimizing photoinduced electron transfer and energy transfer processes of PSs are highlighted. Moreover, the approaches that combine PDT with other therapeutics (e.g., chemotherapy, photothermal therapy, and radiotherapy) and the targeted delivery in cancer cells or tumor tissue are introduced. The main challenges for the clinical application of PSs are also discussed.

Dual-Dynamic-Bond Cross-Linked Antibacterial Adhesive Hydrogel Sealants with On-Demand Removability for Post-Wound-Closure and Infected Wound Healing.

Abstract: The design and development of a smart bioadhesive hydrogel sealant with self-healing and excellent antibacterial activity to achieve high wound closure effectiveness and post-wound-closure care is highly desirable in clinical applications. In this work, a series of adhesive antioxidant antibacterial self-healing hydrogels with promising traits were designed through dual-dynamic-bond cross-linking among ferric iron (Fe), protocatechualdehyde (PA) containing catechol and aldehyde groups and quaternized chitosan (QCS) to enable the closure of skin incisions and promotion of methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing. The dual-dynamic-bond cross-linking of a pH-sensitive coordinate bond (catechol-Fe) and dynamic Schiff base bonds with reversible breakage and re-formation equips the hydrogel with excellent autonomous healing and on-demand dissolution or removal properties. Additionally, the hydrogel presents injectability, good biocompatibility and antibacterial activity, multifunctional adhesiveness, and hemostasis as well as NIR responsiveness. The in vivo evaluation in a rat skin incision model and infected full-thickness skin wound model revealed the high wound closure effectiveness and post-wound-closure care of the smart hydrogels, demonstrating its great potential in dealing with skin incisions and infected full-thickness skin wounds.

A Magnetofluorescent Carbon Dot Assembly as an Acidic H 2 O 2 -Driven Oxygenerator to Regulate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy

Abstract: Recent studies indicate that carbon dots (CDs) can efficiently generate singlet oxygen (1 O2 ) for photodynamic therapy (PDT) of cancer. However, the hypoxic tumor microenvironment and rapid consumption of oxygen in the PDT process will severely limit therapeutic effects of CDs due to the oxygen-dependent PDT. Thus, it is becoming particularly important to develop a novel CD as an in situ tumor oxygenerator for overcoming hypoxia and substantially enhancing the PDT efficacy. Herein, for the first time, magnetofluorescent Mn-CDs are successfully prepared using manganese(II) phthalocyanine as a precursor. After cooperative self-assembly with DSPE-PEG, the obtained Mn-CD assembly can be applied as a smart contrast agent for both near-infrared fluorescence (FL) (maximum peak at 745 nm) and T1 -weighted magnetic resonance (MR) (relaxivity value of 6.97 mM-1 s-1 ) imaging. More interestingly, the Mn-CD assembly can not only effectively produce 1 O2 (quantum yield of 0.40) but also highly catalyze H2 O2 to generate oxygen. These collective properties of the Mn-CD assembly enable it to be utilized as an acidic H2 O2 -driven oxygenerator to increase the oxygen concentration in hypoxic solid tumors for simultaneous bimodal FL/MR imaging and enhanced PDT. This work explores a new biomedical use of CDs and provides a versatile carbon nanomaterial candidate for multifunctional nanotheranostic applications.