A multifunctional theranostic platform based on photosensitizer-loaded plasmonic vesicular assemblies of gold nanoparticles (GNPs) is developed for effective cancer imaging and treatment. The gold vesicles (GVs) composed of a monolayer of assembled GNPs show strong absorbance in the near-infrared (NIR) range of 650–800 nm, as a result of the plasmonic coupling effect between neighboring GNPs in the vesicular membranes. The strong NIR absorption and the capability of encapsulating photosensitizer Ce6 in gold vesicles (GVs) enable tri-modality NIR fluorescence/thermal/photoacoustic imaging-guided synergistic photothermal/photodynamic therapy (PTT/PDT) with improved efficacy. The Ce6-loaded GVs (GV-Ce6) have the following characteristics: i) high Ce6 loading efficiency (up to ~18.4 wt%; ii) enhanced cellular uptake efficiency of Ce6; iii) simultaneous tri-modality NIR fluorescence/thermal/photoacoustic imaging; iv) synergistic PTT/PDT treatment with improved efficacy using single wavelength continuous wave laser irradiation.
Hierarchical assembling of gold nanoparticles (GNPs) allows one to engineer the localized surface plasmon resonance (LSPR) peaks to the near-infrared (NIR) region for enhanced photothermal Therapy (PTT). Herein we report a novel theranostic platform based on biodegradable plasmonic gold nanovesicles for photoacoustic (PA) Imaging and PTT. The disulfide bond (S-S) termed PEG-b-PCL block copolymer graft allows dense packing of GNPs during the assembly process and induces ultra-strong plasmonic coupling effect between adjacent GNPs. The strong NIR absorption induced by plasmon coupling and very high photothermal conversion efficiency (η= 37 %) enable simultaneous thermal/PA imaging and enhanced PTT efficacy with improved clearance of the dissociated particles after the completion of PTT. These vesicle-architectures assembling of various nanocrystals with tailored optical, magnetic, and electronic properties opens new possibilities for constructing multifunctional biodegradable platforms for biomedical applications, particularly in cancer theranotics.
Two-dimensional transition metal carbides and nitrides known as MXenes, with a general formula of Mn+1Xn (n = 1-3), integrate the advantages of metallic conductive transition metals with large groups of carbides, nitrides, or carbonitrides. They have led to a burgeoning research interest in biomedical applications due to their ultrathin structure and fascinating physiochemical (electronic, optical, magnetic, etc.) properties. In this review, we summarize recent advances in biomedical applications for MXenes. We first introduce the preparation methods and surface modifications with respect to MXenes. Their unique properties are then elaborated. Thirdly, we highlight their various biomedical applications, such as with biosensors, antibacterial materials, bioimaging probes, therapeutics, and theranostics. In the end, the current challenges and new opportunities for MXenes in regard to their biomedical applications are also discussed.
Novel theranostics based on photosensitizer‐conjugated carbon dots is reported. The prepared C‐dots–Ce6 has good stability and high water dispersibility and solubility, non‐cytotoxicity, good biocompatibility, enhanced photosensitizer fluorescence detection and remarkable photodynamic efficacy upon irradiation. The C‐dots–Ce6 conjugate is a good candidate with excellent imaging and tumor‐homing ability for NIR fluorescence imaging monitored PDT treatment.
Glucose oxidase (GOx) is an endogenous oxido-reductase that is widely distributed in living organisms. Over recent years, GOx has attracted increasing interest in the biomedical field due to its inherent biocompatibility, non-toxicity, and unique catalysis against β-d-glucose. GOx efficiently catalyzes the oxidization of glucose into gluconic acid and hydrogen peroxide (H2O2), which can be employed by various biosensors for the detection of cancer biomarkers. Various cancer therapeutic strategies have also been developed based on the catalytic chemistry of GOx: (1) the consumption of glucose provides an alternative strategy for cancer-starvation therapy; (2) the consumption of oxygen increases tumor hypoxia, which can be harnessed for hypoxia-activated therapy; (3) the generation of gluconic acid enhances the acidity of the tumor microenvironment, which can trigger pH-responsive drug release; (4) the generation of H2O2 increases the levels of tumor oxidative stress, and the H2O2 can be converted into toxic hydroxyl radicals that can kill cancer cells upon exposure to light irradiation or via the Fenton reaction. More importantly, GOx can be combined with other enzymes, hypoxia-activated prodrugs, photosensitizers or Fenton's reagents, to generate multi-modal synergistic cancer therapies based on cancer starvation therapy, hypoxia-activated therapy, oxidation therapy, photodynamic therapy, and/or photothermal therapy. Such multi-modal approaches are anticipated to exert a stronger therapeutic effect than one therapeutic mode alone. Thus, maximizing the potential of GOx in a biomedical context will offer novel clinical solutions to diagnose and treat cancer. In this tutorial review, we introduce the recent advances of GOx in cancer diagnosis and treatment. We then emphasize the design principles and biomedical applications of GOx-based biosensors and cancer therapeutic approaches. Finally, we discuss the challenges and future prospects of GOx-based catalytic systems in biomedicine.
Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and π-π stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT.
Chemodynamic therapy (CDT) is an emerging therapy method that kills cancer cells by converting intracellular hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (•OH). To overcome the current limitations of the insufficient endogenous H2O2 and the high concentration of glutathione (GSH) in tumor cells, an intelligent nanocatalytic theranostics (denoted as PGC‐DOX) that possesses both H2O2 self‐supply and GSH‐elimination properties for efficient cancer therapy is presented. This nanoplatform is constructed by a facile one‐step biomineralization method using poly(ethylene glycol)‐modified glucose oxidase (GOx) as a template to form biodegradable copper‐doped calcium phosphate nanoparticles, followed by the loading of doxorubicin (DOX). As an enzyme catalyst, GOx can effectively catalyze intracellular glucose to generate H2O2, which not only starves the tumor cells, but also supplies H2O2 for subsequent Fenton‐like reaction. Meanwhile, the redox reaction between the released Cu2+ ions and intracellular GSH will induce GSH depletion and reduce Cu2+ to Fenton agent Cu+ ions, and then trigger the H2O2 to generate •OH by a Cu+‐mediated Fenton‐like reaction, resulting in enhanced CDT efficacy. The integration of GOx‐mediated starvation therapy, H2O2 self‐supply and GSH‐elimination enhanced CDT, and DOX‐induced chemotherapy, endow the PGC‐DOX with effective tumor growth inhibition with minimal side effects in vivo.
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