Enzyme responsive luminescent ruthenium(II) cephalosporin probe for intracellular imaging and photoinactivation of antibiotics resistant bacteria

The Főrster resonance energy transfer (FRET) based luminescent ruthenium(II) cephalosporin probe has been designed and synthesized, which can be selectively activated by endogenous β-lactamases and thus provided a localized and specific intracellular luminescence imaging and photoinactivation of drug resistant bacterial pathogens

Recent Advances of Light-Mediated Theranostics

Currently, precision theranostics have been extensively demanded for the effective treatment of various human diseases. Currently, efficient therapy at the targeted disease areas still remains challenging since most available drug molecules lack of selectivity to the pathological sites. Among different approaches, light-mediated therapeutic strategy has recently emerged as a promising and powerful tool to precisely control the activation of therapeutic reagents and imaging probes in vitro and in vivo, mostly attributed to its unique properties including minimally invasive capability and highly spatiotemporal resolution. Although it has achieved initial success, the conventional strategies for light-mediated theranostics are mostly based on the light with short wavelength (e.g., UV or visible light), which may usually suffer from several undesired drawbacks, such as limited tissue penetration depth, unavoidable light absorption/scattering and potential phototoxicity to healthy tissues, etc. Therefore, a near-infrared (NIR) light-mediated approach on the basis of long-wavelength light (700-1000 nm) irradiation, which displays deep-tissue penetration, minimized photo-damage and low autofluoresence in living systems, has been proposed as an inspiring alternative for precisely phototherapeutic applications in the last decades. Despite numerous NIR light-responsive molecules have been currently proposed for clinical applications, several inherent drawbacks, such as troublesome synthetic procedures, low water solubility and limited accumulation abilities in targeted areas, heavily restrict their applications in deep-tissue therapeutic and imaging studies. Thanks to the amazing properties of several nanomaterials with large extinction coefficient in the NIR region, the construction of NIR light responsive nanoplatforms with multifunctions have become promising approaches for deep-seated diseases diagnosis and therapy. In this review, we summarized various light-triggered theranostic strategies and introduced their great advances in biomedical applications in recent years. Moreover, some other promising light-assisted techniques, such as photoacoustic and Cerenkov radiation, were also systemically discussed. Finally, the potential challenges and future perspectives for light-mediated deep-tissue diagnosis and therapeutics were proposed.Published versio

Metallic Nanoparticle‐Enabled Sensing of a Drug‐of‐Abuse: An Attempt at Forensic Application

γ-Hydroxybutyric acid (GHB) functions as a depressant on the central nerve system and serves as a pharmaceutical agent in the treatment of narcolepsy and alcohol withdraw. In recent years, GHB has been misused as a recreational drug due to its ability to induce euphoric feelings. Moreover, it has gained increasing attention as a popular drug of abuse that is frequently related to drug-facilitated sexual assaults. At the moment, detection methods based on chromatography exhibit extraordinary sensitivity for GHB sensing. However, such techniques require complicated sample treatment prior to analysis. Optical sensors provide an alternative approach for rapid and simple analysis of GHB samples. Unfortunately, currently reported probes are mostly based on hydrogen bonding to recognize GHB, and this raises concerns about, for example, the lack of specificity. In this work, we report a bioinspired strategy for selective sensing of GHB. The method is based on specific enzyme recognition to allow highly selective detection of GHB with minimum interference, even in a complex sample matrix (e. g., simulated urine). In addition, the result can be obtained by either quantitative spectroscopy analysis or colorimetric change observed by the naked-eye, thus demonstrating its potential application in drug screening and forensic analysis.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversityB.X.acknowledges the financial supports from SPMS–M4082042.110, National Natural Science Foundation of China (NSFC)(No. 51929201), Tier 1 RG5/18(S), MOE 2017-T2-2-110 and A*Star SERCA1983c0028 (M4070319) in Nanyang Technological University(NTU)

Multispectral manifestation of redox dynamics and pathological progression based on integrated NIR fluorescent paradigms

As an essential signalling mediator, multiple redox radicals, including reactive oxygen and nitrogen species (ROS/RNS), have been extensively authenticated as significant functional regulators involved in many essential physiological processes such as cellular signal transduction, intermediary metabolism, pathogenesis, as well as immune or inflammatory response. The altered redox balances may cause severe oxidative or nitrosative stress that is closely implicated in the etiology and pathologies of diverse human diseases including cancers, neurodegenarative diseases and bacterial infection. Moreover, mounting investigations have indicated that the generation of ROS or RNS is not static, but rather, their excess or shortage, or even spatiotemporal distributions and correlations are always processing in a highly dynamic and programmed precision. Such biological diversities of free radicals provide great possibilities to act as ideal endogenous biomarkers for spatiotemporally dynamic profiling of the pathophysiological implications in complicated living settings. To this end, by taking advantages of tissue penetrable feature and multiplexing luminescence from NIR laser responsive lanthanide nanoprobes, we recently develop some innovative approaches for simultaneous screening of various redox species, and, significantly, for dynamic profiling of their intricate correlations with pathophysiological implications and therapeutic assessment through multispectral optoacoustic Tomography (MSOT) and NIR fluorescent imaging.Published versio

Tumour enzyme affinity mediated peptide molecular crowding for targeted disruption of hyperactivated glucose uptake

An unconventional environment-responsive molecular crowding via specific binding between small molecule peptide inhibitor derivatives and an overexpressed tumour enzyme has been developed. Assemblies of such short peptides selectively localize on tumour surfaces and exhibited unique functions in disrupting hyperactivated glucose uptake, providing novel insights towards strategic tumour treatment.Agency for Science, Technology and Research (A*STAR)Nanyang Technological UniversityThe authors acknowledge financial support from the National Natural Science Foundation of China (NSFC) (No. 51929201), Tier 1 RG6/20 and A*Star SERC A1983c0028 (M4070319), and A20E5c0090 from Nanyang Technological University (NTU)

Recent advances of material-decorated photosynthetic microorganisms and their aspects in biomedical applications

Photosynthetic microorganisms, especially microalgae and cyanobacteria, have been well-developed as attractive biomaterials with their eigen oxygen production capability, high-value metabolites, and diverse biofunctionalities. Moreover, recent advances in nanotechnology and materials sciences also witnessed promising prospects by integrating unique properties of distinctive functional materials with photosynthetic microorganisms to construct material-decorated photosynthetic microorganisms (MPMs) that can foster diversified biomedical functions. These integrated MPM hybrids can serve as smart cargoes for targeting therapeutic delivery, mainly due to their modifiable surface morphology, actuated propulsion, good biocompatibility, and spacious encapsulating effect. Moreover, attributing to the intrinsic oxygenation and autofluorescence, the MPMs can also act as the oxygen supplier to conduct various oxygen-related modulation and image-guided therapies. This review systematically outlines the recent advances of MPMs as unique platforms to achieve their targeted drug delivery. In addition, promising applications of these micro-sized biohybrids for in situ oxygen modulation and oxygen-related therapeutic manipulation are also summarized. Some relevant applications regarding their synergistic theranostics and the feasibility as the macro-sized scaffold for tissue engineering and wound healing are also carefully covered. Finally, current challenges and future perspectives of these multifunctional material-microbe hybridized conjugations are also discussed.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Submitted/Accepted versionThis work was supported by MOE Tier 1 RG4/22, RG6/20, RG69/21, MoE AcRF Tier 1 Theme RT7/22, A*Star SERC A1983c0028, A20E5c0090, awarded at Nanyang Technological University (NTU), National Natural Science Foundation of China (NSFC) (Nos. 51929201 and 22007083)

Lanthanide-doped upconversion nanoparticles meet the needs for cutting-edge bioapplications: Recent progress and perspectives

The rise of biological frontier fields such as precision theranostics, gene editing, optogenetics, etc. introduces the best opportunities and unprecedented challenges at the same time to the bioapplication of luminescent nanomaterials. Because of the merits of photon upconversion characteristics and high stability, tunable structure and excitation dynamics, and sharp emissions, the lanthanide-doped upconversion nanoparticle (UCNP) is considered to be a highly competitive candidate to meet these challenges. Indeed, UCNPs have attracted extensive attention in diverse cutting-edge bioapplication fields ranging from near-zero background biosensing, deep tissue bioimaging, precision nanomedicine, and remote biomanipulation since the first development in the early 2000s. Recently, with the increasing maturity of upconversion synthesis technology and the deep integration of multiple disciplines, the biological application research of upconversion has achieved many new breakthroughs. Herein, we summarize the latest bioapplication research progress of UCNPs in the fields of sensing, imaging, therapy, optogenetics, etc. Ultimately, current challenges and perspectives in this field are discussed.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversityZ.Z. acknowledges the financial support from National Natural Science Foundation of China (NSFC) (No. 22007083), Zhejiang Provincial Natural Science Foundation of China (Grant No. LQ20B010010), and Science Foundation of Zhejiang Sci-Tech University (ZSTU) under Grant No.19062410-Y. B.X. acknowledges the financial support from Tier 1 RG5/18 (S), RG6/20, MOE 2017-T2-2-110, Start-Up Grant (SUG), A*Star SERC A1983c0028 (M4070319), A20E5c0090, and the National Natural Science Foundation of China (NSFC) (No. 51929201)