Bio-Inspired Ionic Skin for Theranostics

The first-generation ionic skins demonstrate great advantages in the tunable mechanical properties, high transparency, ionic conductivities, and multiple sensory capacities. However, little attention is paid to the interfacial interactions among the ambient environment, natural organisms, and the artificial skins. In particularly, current ionic skins based on traditional synthetic hydrogels suffer from dehydration in vitro and lack of substance communication channels with biological tissues. Herein, this work develops a bio-inspired hydrogel to address these key challenges. The hydrogel is designed with natural moisturizing factors to lock water, biomineral ions to transmit signals, and biomimetic gradient channels to transport substances from non-living to living interfaces. It is stable in ambient condition, adhesive and hydrated on mammal skins, and capable of non-invasive point-to-point theranostics. This theranostic ionic skin realizes sensitive detection, enhanced treatment efficacy, and reduced side effects toward major diseases in vitro. It will shed light on the hydrogel bioelectronics with excellent biocompatibility, bio-protection, and bio-integration for human–machine interfaces and intelligent theranostics.     

Advanced Functional Nanomaterials for Theranostics

Nanoscale materials have been explored extensively as agents for therapeutic and diagnostic (i.e., theranostic) applications. Research efforts have shifted from exploring new materials in vitro to designing materials that function in more relevant animal disease models, thereby increasing potential for clinical translation. Current interests include non‐invasive imaging of diseases, biomarkers, and targeted delivery of therapeutic drugs. Here, some general design considerations of advanced theranostic materials and challenges of their use, from both diagnostic and therapeutic perspectives, are discussed. Common classes of nanoscale biomaterials, including magnetic nanoparticles, quantum dots, upconversion nanoparticles, mesoporous silica nanoparticles, carbon‐based nanoparticles, and organic dye‐based nanoparticles, have demonstrated potential for both diagnosis and therapy. Variations such as size control and surface modifications can modulate biocompatibility and interactions with target tissues. The need for improved disease detection and enhanced chemotherapeutic treatments, together with realistic considerations for clinically translatable nanomaterials, will be key driving factors for theranostic agent research in the near future.     

Biomarker-Responsive Nanosystems for Chronic Disease Theranostics

Chronic diseases claim millions of lives every year, and it is of great significance to explore and develop advanced drugs to improve the cure rate of chronic diseases. Nanotheranostics are innovative strategies that enable the integration of diagnostic and therapeutic properties into a single nanosystem. Despite great success in nanotheranostics, their applications of nanotheranostics in nanomedicine are still in their infancy. This is because each disease has its corresponding characteristic pathological microenvironment, which motivates the development of endogenous biomarker-responsive nanosystems to meet the requirements of diagnosis and treatment. Herein, recent progress is presented in biomarker-responsive nanosystems and their biomedical applications. First, biomarker-responsive nanosystems are classified into eight subsections according to the type of chronic diseases, including tumors, cardiovascular diseases, neurological diseases, Wilson's diseases, chronic liver diseases, chronic kidney diseases, diabetes mellitus, and rheumatoid arthritis. In the following, a variety of intriguing applications of biomarkers-responsive nanosystems are briefly elaborated, such as biosensing, diagnosis, therapy, combined theranostics, and early evaluation of therapy effect, etc. Finally, the challenges and future directions from research to clinical translation of these responsive nanosystems are also presented.     

Decoupling Theranostics with Rare Earth Doped Nanoparticles

Theranostic nanoagents targeted for personalized medicine provide a unified platform for therapeutics and diagnostics. To be able to discretely control each individually, allows for safer, more precise, and truly multifunctional theranostics. Rare earth doped nanoparticles can be rationally tailored to best match this condition with the aid of core/shell engineering. In such nanoparticles, the light‐mediated theranostic approach is functionally decoupled—therapeutics or diagnostics are prompted on‐demand, by wavelength‐specific excitation. These decoupled rare earth nanoparticles (dNPs) operate entirely under near‐infrared (NIR) excitation, for minimized light interference with the target and extended tissue depth action. Under heating‐free 806 nm irradiation, dNPs behave solely as high‐contrast NIR‐to‐NIR optical markers and nanothermometers, visualizing and probing the area of interest without prompting the therapeutic effect beforehand. On the contrary, 980 nm NIR irradiation is upconverted by the dNPs to UV/visible light, which triggers secondary photochemical processes, e.g., generation of reactive oxygen species by photosensitizers coupled to the dNPs, causing damage to cancer cells. Additionally, integration of NIR nanothermometry helps to control the temperature in the vicinity of the dNPs avoiding possible overheating and quenching of upconversion (UC) emission, harnessed for photodynamic therapy. Overall, a new direction is outlined in the development of state‐of‐the‐art rare earth based theranostic nanoplatforms.     

Endogenous Stimuli-Activatable Nanomedicine for Immune Theranostics for Cancer

Cancer immunotherapy has witnessed significant advances in the past decade, however challenges associated with immune-related adverse effects and immunosuppressive tumor microenvironment, have hindered their clinical application. Stimuli-activatable nanomedicines hold great potential for improving the efficiency of cancer immunotherapy and minimizing the side effects via tumor-specific accumulation, controllable drug release profile, and combinational therapy by integrating multiple therapeutic regimens. In this review, the recent advances of stimuli-activatable nanomedicines for cancer immunotherapy are first described, with particular focus on endogenous stimuli including pH, glutathione, reactive oxygen species, and excessive enzymes within the tumor microenvironment. Then, the endogenous stimuli-activatable nanomedicines that target tumor cells, immune cells, or periphery immune systems for eliciting sustained systemic immune activation and modulating the immunosuppressive tumor microenvironment, are described. Next, the general mechanisms underlying nanomedicine-based immunotherapy by eliciting anti-tumor immune responses and overcoming immunologic tolerance are described. Further, the emerging application of bioimaging techniques for monitoring immune response and evaluating therapy performance is described. Finally, the authors’ perspectives are provided for the clinical translation of nanomedicine-based cancer immunotherapy.     

Recent Advancements of Nanomedicine in Neurodegenerative Disorders Theranostics

Recent times have witnessed an upsurge in the incidence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Prion disease, and amyotrophic lateral sclerosis. The treatment of the same remains a daunting challenge due to the limited access of therapeutic moieties across the blood–brain barrier. Engineered nanoparticles with a size less than 100 nm provide multifunctional abilities for solving these biomedical and pharmacological issues due to their unique physico‐chemical properties along with capability to cross the blood–brain barrier. Needless to mention, there is a scarcity of review articles summarizing recent developments of various nanomaterials including liposomes, polymeric nanoparticles, metal nanoparticles, and bio‐nanoparticles toward the therapeutic and theranostics applications for various neurodegenerative disorders. Here, a broad spectrum of nanomedicinal approaches to eradicate neurodegenerative disorders is provided, along with a brief account of neuroprotection and neuronal tissue regeneration, current clinical status, issues related to safety, toxicity, challenges, and future outlook.     

Nanomaterials Responsive to Endogenous Biomarkers for Cardiovascular Disease Theranostics

Cardiovascular disease (CVD) is the number one cause of death worldwide, which propels the development of advanced technologies for CVD diagnosis and treatment. Biomarker-responsive nanomaterials are appealing therapeutic platforms that provide new horizons for CVD theranostics. In this review, recent advances in nanomaterials with endogenous biomarkers as stimuli or targets for CVD theranostics is presented. First, the categories of biomarkers involved are comprehensively itemized based on pathological mechanisms including pH, reactive oxygen species, lipids, enzymes, macrophage receptors, subendothelium components, platelet receptors, inflammation, and osteopontin. The role of these biomarkers in bridge-building between nanomaterials and CVD is then presented. Next, the biomedical applications of nanomaterials responsive to endogenous biomarkers as stimuli or targets for the diagnosis and treatment of CVD are elaborated. Finally, the challenges and future research directions of biomarker-responsive nanomaterials in CVD are also discussed. This review will provide scientific guidance to facilitate clinical applications of biomarker-responsive nanomaterials.     

Progress in Light-Responsive Lanthanide Nanoparticles toward Deep Tumor Theranostics

Recently, lanthanide nanoparticles have aroused widespread interest in cancer theranostics by virtue of their excellent photoresponsive performance in deep-seated tumors. The abundant ladder-like energy levels, controllable emission profiles, and unique photoluminescence properties make lanthanide nanoparticles highly efficient for deep skin-penetration of near-infrared (NIR) light, concentrating light energy in tumors with negligible scattering and minimal autofluorescence from biological tissues. High-Z radio-sensitization of lanthanide elements endows lanthanide nanoparticles with a high X-ray attenuation coefficient, making them effective nanoprobes for X-ray-excited bioimaging and synchronous radiotherapy-related treatments. In this review, comprehensive progressions including the synthesis, structural characteristics of lanthanide nanoparticles, and distinct optical excitation mechanisms with NIR and X-ray triggers, are summarized. Advances in NIR-excited and X-ray-triggered cancer imaging methods and therapies are described in detail, wherein NIR-induced luminescence from upconversion nanoparticles and downconversion nanoparticles are introduced separately based on some typical sensitization. Finally, the challenges and opportunities of lanthanide nanoparticles as light-triggered cancer theranostic candidates are discussed, whose translation from bench to bedside still has a long journey to go.     

Amplification of Cerenkov Luminescence Using Semiconducting Polymers for Cancer Theranostics

The therapeutic efficacy of photodynamic therapy is limited by the ability of light to penetrate tissues. Due to this limitation, Cerenkov luminescence (CL) from radionuclides has recently been proposed as an alternative light source in a strategy referred to as Cerenkov radiation-induced therapy (CRIT). Semiconducting polymer nanoparticles (SPNs) have ideal optical properties, such as large absorption cross-sections and broad absorbance, which can be utilized to harness the relatively weak CL produced by radionuclides. SPNs can be doped with photosensitizers and have ≈100% energy transfer efficiency by multiple energy transfer mechanisms. Herein, an optimized photosensitizer-doped SPN is investigated as a nanosystem to harness and amplify CL for cancer theranostics. It is found that semiconducting polymers significantly amplify CL energy transfer efficiency. Bimodal positron emission tomography (PET) and optical imaging studies show high tumor uptake and retention of the optimized SPNs when administered intravenously or intratumorally. Lastly, it is found that photosensitizer-doped SPNs have excellent potential as a cancer theranostics nanosystem in an in vivo tumor therapy study. This study shows that SPNs are ideally suited to harness and amplify CL for cancer theranostics, which may provide a significant advancement for CRIT that are unabated by tissue penetration limits.     

Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics

Human beings are “machines” that use endogenously produced biomolecules as “components” in signaling and for the maintenance of the body. These biomolecules consist of proteins, nucleic acids, and carbohydrates, which can either be extracted from biological substrates or synthesized by chemical/biochemical methods. These biomolecules have the ability to recognize/interact with other biomolecules that are overexpressed in disease cells. For targeted theranostics, strategies to chemically incorporate these natural biomolecules with advanced materials to treat human diseases by imaging‐guided drug delivery or photodynamic/photothermal therapy are proposed, with improved biocompatibility. Herein, recent research on construction of quantum dots, nanoparticles, and 2D material platforms decorated with antibodies, peptides, nucleic acid aptamers, carbohydrates, and folic acid for targeted diagnosis and treatment are summarized and discussed. In addition, the various strategies required to construct effective functional materials for targeted cancer therapy are highlighted. The hope is that this review can inspire and guide those that are interested in the field of biomedicine to rationally design and develop new target‐based theranostic materials.     

Ferric Ion-Driven Chlorin E6 Nanoparticles: Simple and Effective Multimodal Theranostics

Theranostics integrating therapeutic power and imaging exhibit great prospects in precision medicine. It is a big challenge to develop simple and selective theranostic systems for potential clinical translation. Herein the Fe (III) driven assembly of chlorin E6 (Ce6) is reported to form multifunctional nanoparticles. The resulting Fe-Ce6 NPs possess high loading content of photosensitizer Ce6, red-shifted absorption, good colloidal stability, and photostability, and robust photothermal performance. After cellular internalization, Fe-Ce6 NPs can respond to intracellularly enriched glutathione to release Ce6, thus priming photodynamic therapy (PDT) effect, fluorescence, and afterglow luminescence. In vitro and in vivo results prove that Fe-Ce6 NPs remarkably enhance the tumor regression through photothermal therapy and in situ PDT. This study provides a facile and efficient method to construct versatile nanotheranostics for tumor treatment.     

Hierarchical Nanohybrids of Gold Nanorods and PGMA‐Based Polycations for Multifunctional Theranostics

Organic/inorganic nanohybrids hold great importance in fabricating multifunctional theranostics to integrate therapeutic functions with real‐time imaging. Although Au nanorods (NRs) have been employed for theranostics, complicated design of materials limits their practical applications. In this work, new multifunctional theranostic agents are designed and synthesized employing Au NRs with desirable near‐infrared absorbance as the cores. A facile “grafting‐onto” approach is put forward to prepare the series of hierarchical nanohybrids (Au‐PGEA and Au‐PGED) of Au NRs and poly(glycidyl methacrylate)‐based polycations. The resultant nanohybrids can be utilized as gene carriers with high gene transfection performances. The structural effect of polycations on gene transfection is investigated in detail, and Au‐PGEA with abundant hydroxyl groups on the surface exhibits superior performance. Au‐PGEA nanohybrids are further validated to possess remarkable capability of combined photothermal therapy (PTT) and gene therapy (GT) for complementary tumor treatment. Moreover, significantly enhanced computed tomography (CT)/photoacoustic (PA) signals are detected both in vitro and in vivo, verifying the potential of Au‐PGEA for dual‐modal imaging with precise and accurate information. Therefore, these multifunctional nanohybrids fabricated from a simple and straightforward strategy are promising for in vivo dual‐modal CT/PA imaging guided GT/PTT therapy with high antitumor efficacy.     

Cucurbiturils-Mediated Noble Metal Nanoparticles for Applications in Sensing,SERS, Theranostics,and Catalysis

Noble metal nanoparticles (NMNPs), which spring up like mushrooms, are gaining momentum owing to their unique physicochemical characteristics. Cucurbiturils, a class of synthetic macrocycles with intriguing and peculiar host–guest properties, have stimulated tremendous research interest in recent years. The marriage of NMNPs with cucurbiturils is expected to integrate and enhance the excellent characteristics of both components, e.g., precisely controlled particle size, stability, assembly, surface functionality, biocompatibility, tunable optical properties, and high catalytic activities. This review systematically outlines the recent progress on the fabricating strategies and important applications of cucurbiturils-mediated NMNPs in sensing, surface-enhanced Raman scattering, theranostics, and catalysis. A brief outlook on the future development of cucurbiturils-mediated NMNPs is also presented.     

Modus Operandi of Simultaneous Covering Synthesis from Precursor Heterogeneity for Shelled Nanorods for Multipotent Cancer Theranostics

The synthesis of nanostructures using homogeneous precursors in the solution phase is widely used to achieve uniformity and well‐defined morphological control. However, drawbacks such as the lack of diversity due to the limited reaction rate modulation exist. One‐step, core–shell nanorod formation using simultaneous covering synthesis using solid and ionic heterogeneous precursors is proposed in this study. A Te‐Bi₂Te₃/TeO₂ core–shell structure is successfully synthesized by precisely controlling various influencing factors, including concentration, temperature, and pH, and its physicochemical and photochemical properties are thoroughly investigated. The proposed nanostructure overcomes the oxidation susceptibility of Te and can be applied to multipotent cancer theranostics in vitro and in vivo in combination with computed tomography imaging.