Multifunctional organic nanomaterials with ultra-high photothermal conversion efficiency for photothermal therapy and inhibition of cancer metastasis.

Photothermal therapy (PTT) has gained extensive interest in tumor treatments due to its non-invasive and low-toxic nature. However, the currently available photothermal agents (PTAs) mostly show unsatisfactory photothermal conversion efficiency (PCE). Besides, as a local cancer treatment modality, PTT fails to inhibit metastasis of tumors. To address these issues, in this study, two aza-boron-dipyrromethene (aza-BODIPY)-based organic photothermal agents (OPTAs), Fc-aza-BODIPY and TPA-aza-BODIPY, were rationally coined by introducing two strong electron-donating ferrocene (Fc) moieties and two triphenylamine (TPA) rotors, which could boost intramolecular photo-induced electron transfer (PET) and molecular rotation respectively, thereby improving the PCE of aza-BODIPY dyes. After encapsulation of hydrophobic Fc-aza-BODIPY (or TPA-aza-BODIPY) and quercetin with biodegradable PLGA and DSPE-mPEG2000, the resulting nanoparticles (FAQ NPs and TAQ NPs) showed excellent optical properties with PCE of ∼72.0% and ∼79.7% and specific tumor accumulations through enhanced permeability and retention (EPR) effects. Consequently, these two NPs possessed prominent antitumor effects under 880 nm laser irradiation. Moreover, both FAQ NPs and TAQ NPs loaded with quercetin could inhibit tumor metastasis efficiently. These two multifunctional nanomaterials integrating OPTAs and anti-metastasis agents constructed a cooperative treatment program, which may provide a potential opportunity for future clinical cancer treatment.

An Insight into the Combined Toxicity of 3,4-Dichloroaniline with Two-Dimensional Nanomaterials: From Classical Mixture Theory to Structure-Activity Relationship.

The assessment and prediction of the toxicity of engineered nanomaterials (NMs) present in mixtures is a challenging research issue. Herein, the toxicity of three advanced two-dimensional nanomaterials (TDNMs), in combination with an organic chemical (3,4-dichloroaniline, DCA) to two freshwater microalgae (Scenedesmus obliquus and Chlorella pyrenoidosa), was assessed and predicted not only from classical mixture theory but also from structure-activity relationships. The TDNMs included two layered double hydroxides (Mg-Al-LDH and Zn-Al-LDH) and a graphene nanoplatelet (GNP). The toxicity of DCA varied with the type and concentration of TDNMs, as well as the species. The combination of DCA and TDNMs exhibited additive, antagonistic, and synergistic effects. There is a linear relationship between the different levels (10, 50, and 90%) of effect concentrations and a Freundlich adsorption coefficient (KF) calculated by isotherm models and adsorption energy (Ea) obtained in molecular simulations, respectively. The prediction model incorporating both parameters KF and Ea had a higher predictive power for the combined toxicity than the classical mixture model. Our findings provide new insights for the development of strategies aimed at evaluating the ecotoxicological risk of NMs towards combined pollution situations.

Recent Updates on Multifunctional Nanomaterials as Antipathogens in Humans and Livestock: Classification, Application, Mode of Action, and Challenges.

Pathogens cause infections and millions of deaths globally, while antipathogens are drugs or treatments designed to combat them. To date, multifunctional nanomaterials (NMs), such as organic, inorganic, and nanocomposites, have attracted significant attention by transforming antipathogen livelihoods. They are very small in size so can quickly pass through the walls of bacterial, fungal, or parasitic cells and viral particles to perform their antipathogenic activity. They are more reactive and have a high band gap, making them more effective than traditional medications. Moreover, due to some pathogen's resistance to currently available medications, the antipathogen performance of NMs is becoming crucial. Additionally, due to their prospective properties and administration methods, NMs are eventually chosen for cutting-edge applications and therapies, including drug administration and diagnostic tools for antipathogens. Herein, NMs have significant characteristics that can facilitate identifying and eliminating pathogens in real-time. This mini-review analyzes multifunctional NMs as antimicrobial tools and investigates their mode of action. We also discussed the challenges that need to be solved for the utilization of NMs as antipathogens.

Nanomaterials for Removal of Phenolic Derivatives from Water Systems: Progress and Future Outlooks.

Environmental pollution remains one of the most challenging problems facing society worldwide. Much of the problem has been caused by human activities and increased usage of various useful chemical agents that inadvertently find their way into the environment. Triclosan (TCS) and related phenolic compounds and derivatives belong to one class of such chemical agents. In this work, we provide a mini review of these emerging pollutants and an outlook on the state-of-the-art in nanostructured adsorbents and photocatalysts, especially nanostructured materials, that are being developed to address the problems associated with these environmental pollutants worldwide. Of note, the unique properties, structures, and compositions of mesoporous nanomaterials for the removal and decontamination of phenolic compounds and derivatives are discussed. These materials have a great ability to scavenge, adsorb, and even photocatalyze the decomposition of these compounds to mitigate/prevent their possible harmful effects on the environment. By designing and synthesizing them using silica and titania, which are easier to produce, effective adsorbents and photocatalysts that can mitigate the problems caused by TCS and its related phenolic derivatives in the environment could be fabricated. These topics, along with the authors' remarks, are also discussed in this review.

Nanoparticle-Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions.

Cancer immunotherapy is a promising cancer terminator by directing the patient's own immune system in the fight against this challenging disorder. Despite the monumental therapeutic potential of several immunotherapy strategies in clinical applications, the efficacious responses of a wide range of immunotherapeutic agents are limited in virtue of their inadequate accumulation in the tumor tissue and fatal side effects. In the last decades, increasing evidences disclose that nanotechnology acts as an appealing solution to address these technical barriers via conferring rational physicochemical properties to nanomaterials. In this Review, an imperative emphasis will be drawn from the current understanding of the effect of a nanosystem's structure characteristics (e.g., size, shape, surface charge, elasticity) and its chemical modification on its transport and biodistribution behavior. Subsequently, rapid-moving advances of nanoparticle-based cancer immunotherapies are summarized from traditional vaccine strategies to recent novel approaches, including delivery of immunotherapeutics (such as whole cancer cell vaccines, immune checkpoint blockade, and immunogenic cell death) and engineered immune cells, to regulate tumor microenvironment and activate cellular immunity. The future prospects may involve in the rational combination of a few immunotherapies for more efficient cancer inhibition and elimination.

A Modular System for the Design of Stimuli-Responsive Multifunctional Nanoparticle Aggregates by Use of Host-Guest Chemistry.

A self-assembly approach for the design of multifunctional nanomaterials consisting of different nanoparticles (gold, iron oxide, and lanthanide-doped LiYF4 ) is developed. This modular system takes advantage of the light-responsive supramolecular host-guest chemistry of ß-cyclodextrin and arylazopyrazole, which enables the dynamic and reversible self-assembly of particles to spherical nanoparticle aggregates in aqueous solution. Due to the magnetic iron oxide nanoparticles, the aggregates can be manipulated by an external magnetic field leading to the formation of linear structures. As a result of the integration of upconversion nanoparticles, the aggregates are additionally responsive to near-infrared light and can be redispersed by use of the upconversion effect. By varying the nanoparticle and linker concentrations the composition, size, shape, and properties of the multifunctional nanoparticle aggregates can be fine-tuned.

Multifunctional nanomaterials for smart wearable diabetic healthcare devices.

Wearable diabetic healthcare devices have attracted great attention for real-time continuous glucose monitoring (CGM) using biofluids such as tears, sweat, saliva, and interstitial fluid via noninvasive ways. In response to the escalating global demand for CGM, these devices enable proactive management and intervention of diabetic patients with incorporated drug delivery systems (DDSs). In this context, multifunctional nanomaterials can trigger the development of innovative sensing and management platforms to facilitate real-time selective glucose monitoring with remarkable sensitivity, on-demand drug delivery, and wireless power and data transmission. The seamless integration into wearable devices ensures patient's compliance. This comprehensive review evaluates the multifaceted roles of these materials in wearable diabetic healthcare devices, comparing their glucose sensing capabilities with conventionally available glucometers and CGM devices, and finally outlines the merits, limitations, and prospects of these devices. This review would serve as a valuable resource, elucidating the intricate functions of nanomaterials for the successful development of advanced wearable devices in diabetes management.

Exploring luminescent carbon dots derived from syrup bottle waste and curcumin for potential antimicrobial and bioimaging applications.

In this study, we utilized a navel hybrid material, prepared by fusing fluorescent Carbon Dots SyCDs, derived from syrup bottles, with curcumin. This innovative approach not only offers significant advancements in antimicrobial activity and bioimaging but also represents a stride in sustainable and eco-friendly nanotechnology. The core of our study is the development of an efficient, cost-effective, and environmentally conscious method for synthesizing SyCDs. This is achieved by repurposing waste syrup bottles, thus addressing the pressing issue of plastic waste. The incorporation of curcumin, renowned for its biological properties, enhances the luminescent characteristics of SyCDs and augments their functionality. This combination overcomes the inherent limitations of curcumin when used in isolation. The hybrid material exhibits enhanced antimicrobial properties and proves to be a potent alternative to conventional fluorescent dyes for bioimaging, marking a substantial leap in the field of sustainable nanomaterials. Our work not only demonstrates the versatile applications of luminescent SyCDs in health and environmental science but also underscores the potential of sustainable approaches in addressing global environmental challenges. This study, represents a significant contribution to the domain of sustainable nanotechnology, highlighting the transformative power of integrating waste management with advanced material science.

Nanomaterials Mediated Multimodal Combined Treatment for Cancer.

Cancer is still one of the most serious diseases that threaten human life. In the past decades, nanomaterials have been found to possess excellent advantages, including controlled drug release, easy modification surface, good biocompatibility, typical optical property, useful chemical ability, and so on, due to which they have become the rising star in the application for multimodal combined cancer treatment (MCT). The emerging avenues of photodynamic therapy, photothermal therapy, magnetocaloric therapy, chemodynamic therapy, immunotherapy, and gene therapy are integrated systematically and intelligently with the traditional methods, realizing the therapeutic effect in cancer treatment. However, there are still several challenges in the development of nanomaterials for MCT, such as the construction of complex systems, deep penetration into solid tumors, effective immune activation at tumor sites, and so on. This review describes the application of multifunctional nanomaterials in the field of MCT for tumor, proposing some suggestions and ideas for future development.

Advanced Flame Spray Pyrolysis (FSP) Technologies for Engineering Multifunctional Nanostructures and Nanodevices.

Flame spray pyrolysis (FSP) is an industrially scalable technology that enables the engineering of a wide range of metal-based nanomaterials with tailored properties nanoparticles. In the present review, we discuss the recent state-of-the-art advances in FSP technology with regard to nanostructure engineering as well as the FSP reactor setup designs. The challenges of in situ incorporation of nanoparticles into complex functional arrays are reviewed, underscoring FSP's transformative potential in next-generation nanodevice fabrication. Key areas of focus include the integration of FSP into the technology readiness level (TRL) for nanomaterials production, the FSP process design, and recent advancements in nanodevice development. With a comprehensive overview of engineering methodologies such as the oxygen-deficient process, double-nozzle configuration, and in situ coatings deposition, this review charts the trajectory of FSP from its foundational roots to its contemporary applications in intricate nanostructure and nanodevice synthesis.

Simple preparation of POxylated nanomaterials for cancer chemo-PDT/PTT.

Near infrared (NIR) light-responsive nanomaterials hold potential to mediate combinatorial therapies targeting several cancer hallmarks. When irradiated, these nanomaterials produce reactive oxygen species (photodynamic therapy) and/or a temperature increase (photothermal therapy). These events can damage cancer cells and trigger the release of drugs from the nanomaterials' core. However, engineering nanomaterials for cancer chemo-photodynamic/photothermal therapy is a complex process. First, nanomaterials with photothermal capacity are synthesized, being then loaded with photosensitizers plus chemotherapeutics, and, finally functionalized with polymers for achieving suitable biological properties. To overcome this limitation, in this work, a novel straightforward approach to attain NIR light-responsive nanosystems for cancer chemo-photodynamic/photothermal therapy was established. Such was accomplished by synthesizing poly(2-ethyl-2-oxazoline)-IR780 amphiphilic conjugates, which can be assembled into nanoparticles with photodynamic/photothermal capabilities that simultaneously encapsulate Doxorubicin (DOX/PEtOx-IR NPs). The DOX/PEtOx-IR NPs presented a suitable size and surface charge for cancer-related applications. When irradiated with NIR light, the DOX/PEtOx-IR NPs produced singlet oxygen as well as a smaller thermic effect that boosted the release of DOX by 1.7-times. In the in vitro studies, the combination of DOX/PEtOx-IR NPs and NIR light could completely ablate breast cancer cells (viability ≈ 4 %), demonstrating the enhanced outcome arising from the nanomaterials' chemo-photodynamic/photothermal therapy.

Encapsulation of 67Cu therapeutic radiometal in luminescent lanthanide phosphate core and core-shell nanoparticles.

Copper-67 (67Cu) has physical characteristics useful for both therapy and imaging. However, its applicability has been hindered by the complexity of obtaining large quantities of a product with high specific activity. With the advancement of 67Cu production methods, suitable radioisotope carriers are sought. Lanthanide phosphate nanoparticles have demonstrated their multifunctional characteristics for biomedical applications and, more recently, their potential in radiopharmaceuticals. Thus, we produced luminescent lanthanide phosphate nanoparticles with core and core-shell structures, incorporating 67Cu during their synthesis. The nanoparticles exhibited hexagonal crystalline structure and spherical morphology with sizes below 6 nm. The luminescent colloidal suspensions evidenced the characteristic 5D0-7FJ for Eu3+, providing the red color under UV light. A radiochemical yield of 67Cu >95% was obtained with both core and core-shell LaPO4:Eu. The core-shell nanoparticles reduced the release of 67Cu by a factor of ∼2 over that from the core, which continuously decreased with time. Multifunctional LnPO4 nanoparticles have the potential to be used as a carrier of single or multiple radioisotopes to enhance image-guided targeted nano-radiopharmaceutical therapy.

Interfacially responsive electron transfer and matter conversion by polydopamine-mediated nanoplatforms for advancing disease theranostics.

Polydopamine (PDA) is an artificial melanin polymer that has been spotlighted due to its extraordinary optoelectronic characteristics and advance theranosctic applications in biomaterial fields. Moreover, interactions on the nano-bio interface interplay whereby substances exchange in response to endogenous or exogenous stimuli, and electron transfer driven by light, energy-level transitions, or electric field greatly affect the functional performance of PDA-modified nanoparticles. The full utilization of potential in PDA's interfacial activities, optoelectrical properties and related responsiveness is therefore an attractive means to construct advanced nanostructures for regulating biological processes and metabolic pathways. Herein, we strive to summarize recent advances in the construction of functional PDA-based nanomaterials with state-of-the-art architectures prepared for modulation of photoelectric sensing and redox reversibility, as well as manipulation of photo-activated therapeutics. Meanwhile, contributions of interfacial electron transfer and matter conversion are highlighted by discussing the structure-property-function relationships and the biological effects in their featured applications including disease theranostics, antibacterial activities, tissue repair, and combined therapy. Finally, the current challenges and future perspectives in this emerging research field will also be outlined. Recent advances on polydopamine-based nanotherapeutics with an emphasis on their interfacial activities, optoelectrical properties and related responsiveness are reviewed for providing insightful guidance to the rational design of integrated theranostic nanoplatforms with high performance in the biomedical fields. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Engineered fabrication of EGCG-UV absorber conjugated nano-assemblies for antioxidative sunscreens with broad-band absorption.

Applying sunscreen is a common, convenient, and effective measure to protect skin from ultraviolet (UV) damage, but most of UV absorbers in the present commercially available sunscreens are accompanied with the insufficiencies in terms of efficacy and biosafety. The use of nanotechnology to combine conventional UV absorbers with biocompatible natural products is a feasible strategy to combat these deficiencies. Herein, a simple, green and engineering preparation of broad-band sunscreens was demonstrated by the molecular assembly of a UV absorber aminobenzoic acid (ABA) and polyphenol extracted from green tea (EGCG). Spherical and negatively-charged EGCG/ABA nanoparticles (EA NPs) were simply synthesized with a wide range of particle size from 54.6 to 715.1 nm. These NPs had the satisfactory biocompatibility and antioxidative activity, and could protect fibroblasts from oxidative-stress damage. The formulations containing 10 wt% EA NPs further exhibited broad-spectrum UV absorption and lower UV transmittance than commercial sunscreens. It is believed that this study would spur the utilization of natural reproducible sources for developing biosafe sunscreens with strong anti-UV capability. Indeed, this simple nanotechnology aimed at tackling the biosafe risk of conventional UV absorbers provides a feasible solution strategy with green tea extracts.

"Three-in-one" Zr-MOF Multifunctional Carrier-mediated Fluorescent and Colorimetric Dual-signal Readout Biosensing Platform to Enhance Analytical Performance.

To address the urgent demand for sensitive and stable detection applications, significant efforts have been made in the development of dual-signal readout assays for precise target detection and timely health risk control. Here, a new nanomaterial, Pt@PCN-224-HRP-initiator DNA (PP-HRP-iDNA), was exploited to construct a dual-signal readout biosensing platform. Zr-MOF (PCN-224) was loaded with as many Pt nanoparticles (NPs) and as much horseradish peroxidase (HRP) as possible to enhance the brightness of the colorimetric signal recognizable to the naked eye while also acting as a gatekeeper to protect the enzyme activity and ensuring the stability of the assay process. Moreover, the Pt NPs and HRP displayed a synergistic catalytic effect, which promoted the sensitivity of detection. Further, the formation of the Zr-O-P bond eliminated the instability of the interactions between PCN-224 and iDNA in a controllable manner. After the immunoreaction, iDNA stimulated a hybridization chain reaction, resulting in a significant reduction of the fluorescent DNA in the supernatant and a fluorescent signal change. Subsequently, the PP-HRP-iDNA probe implemented UV-light response (450 nm) where 3,3',5,5'-tetramethylbenzidine was used as a substrate for the colorimetric signal readout. By virtue of the nanomaterial-modulated transduction mechanism and the antigen-antibody interactions, this dual-signal biosensor displays high sensitivity, with a limit of detection of 0.65 pg/mL for aflatoxin B1 and 4 CFU/mL for Salmonella enteritidis, suggesting the detection potential of the biosensing platform for analyzing various targets.

Thermosensitive hydrogel-functionalized gold nanorod/mesoporous MnO2 nanoparticles for tumor cell-triggered drug delivery.

MnO2 owns distinct redox, imaging, and degradable properties corresponding to the tumor microenvironment. However, the onefold structure and non-modifiable property cause many obstacles to anticancer applications. In this report, we first prepared a typical core-shell gold nanorod (GNR)/manganese dioxide (MnO2) nanoparticles (GNR/MnO2 NPs). Interestingly, the MnO2 had a mesoporous channel and modifiable hydroxyl group (OH). Here, the unique 'OH' groups were modified and further grafted with poly(N-isopropylacrylamide-co-acrylic acid) (PNA). As a dual-sensitive hydrogel, it was selected as the thermal/pH-sensitive component in the hybrid nanoparticles (GNR/MnO2/PNA NPs). The anticancer drug doxorubicin hydrochloride (DOX) was selected and loaded into the hybrid nanoparticles (GNR/MnO2/PNA-DOX NPs). The GNR/MnO2/PNA NPs achieved satisfying drug-loading efficiency and glutathione (GSH)/pH/thermal-responsive drug-controlled release. As a side benefit, the GNR/MnO2/PNA NPs showed potential as excellent near-infrared (NIR)-excited nanoplatforms for photothermal therapy (PTT). Delightedly, the studies demonstrated that the GNR/MnO2/PNA-DOX NPs showed a noticeable killing effect on tumor cells, whether it is tumor cell-triggered drug release or photothermal effect. Besides, it not only could enhance mitochondrial damage but also could inhibit the migration and invasion of tumor cells. Quite the reverse, it had little negative impact on normal cells. The feature can prevent anticancer drugs and nanoparticles from killing normal cells. Consequently, GNR/MnO2/PNA NPs have potential applications in drug delivery and synergistic therapy due to these advantageous features.

2D Nanomaterials for Cancer Theranostic Applications.

2D nanomaterials with unique nanosheet structures, large surface areas, and extraordinary physicochemical properties have attracted tremendous interest. In the area of nanomedicine, research on graphene and its derivatives for diverse biomedical applications began as early as 2008. Since then, many other types of 2D nanomaterials, including transition metal dichalcogenides, transition metal carbides, nitrides and carbonitrides, black phosphorus nanosheets, layered double hydroxides, and metal-organic framework nanosheets, have been explored in the area of nanomedicine over the past decade. In particular, a large surface area makes 2D nanomaterials highly efficient drug delivery nanoplatforms. The unique optical and/or X-ray attenuation properties of 2D nanomaterials can be harnessed for phototherapy or radiotherapy of cancer. Furthermore, by integrating 2D nanomaterials with other functional nanoparticles or utilizing their inherent physical properties, 2D nanomaterials may also be engineered as nanoprobes for multimodal imaging of tumors. 2D nanomaterials have shown substantial potential for cancer theranostics. Herein, the latest progress in the development of 2D nanomaterials for cancer theranostic applications is summarized. Current challenges and future perspectives of 2D nanomaterials applied in nanomedicine are also discussed.

Multimodal/Multifunctional Nanomaterials in (Bio)electrochemistry: Now and in the Coming Decade.

Multifunctional nanomaterials, defined as those able to achieve a combined effect or more than one function through their multiple functionalization or combination with other materials, are gaining increasing attention in the last years in many relevant fields, including cargo targeted delivery, tissue engineering, in vitro and/or in vivo diseases imaging and therapy, as well as in the development of electrochemical (bio)sensors and (bio)sensing strategies with improved performance. This review article aims to provide an updated overview of the important advances and future opportunities exhibited by electrochemical biosensing in connection to multifunctional nanomaterials. Accordingly, representative aspects of recent approaches involving metal, carbon, and silica-based multifunctional nanomaterials are selected and critically discussed, as they are the most widely used multifunctional nanomaterials imparting unique capabilities in (bio)electroanalysis. A brief overview of the main remaining challenges and future perspectives in the field is also provided.

Nanomedicine solutions to intricate physiological-pathological barriers and molecular mechanisms of tumor multidrug resistance.

Cancer multidrug resistance (MDR) has been a fatal factor for the failure of clinical chemotherapy, accompanying with tumor metastasis and recurrence. The mechanisms of MDR are extremely complicated, diversifying from tumor physiological-pathological barriers to molecular mechanisms of cellular factors. Especially, certain hard biological barriers (such as tumor tissue barriers and tumor subcellular compartments) are found to have close relationship with multidrug resistance, and increasing attentions are paid to address the MDR-related physiopathologic barriers for optimal drug distribution and bioavailability. Molecular and genetic factors of multidrug resistance are also gradually disclosed, such as decreased drug influx, increased drug efflux, altered drug targets, aberrant apoptotic pathway and activated DNA repair. To cope with these challenges, diverse nanomedicine solutions have been developed for overcoming physiological-pathological barriers and molecular mechanisms in the treatment of drug-resistant tumors. This review first introduces that multifunctional nanomedicines break through sequential physiological-pathological barriers to reverse MDR, including prolonged in vivo blood circulation, improved drug tumor penetration and intratumoral distribution, increased cellular internalization, optimized subcellular targeting and sufficient drug release. For another, nanomedicine solutions also show immense potentials on provoking multiple mechanisms for MDR reversal, such as decreasing drug efflux, strengthening tumor apoptosis and suppressing anti-apoptosis.

Application of Multifunctional Nanomaterials in Radioprotection of Healthy Tissues.

Radiotherapy has been extensively used in clinic for malignant tumors treatment. However, a severe challenge of it is that the ionizing radiation needed to kill tumors inevitably causes damage to surrounding normal tissues. Although some of the molecular radioprotective drugs, such as amifostine, have been used as clinical adjuvants to radio-protect healthy tissues, their shortcomings such as short systemic circulation time and fast biological clearing from the body largely hinder the sustained bioactivity. Recently, with the rapid development of nanotechnology in the biological field, the multifunctional nanomaterials not only establish powerful drug delivery systems to improve the molecular radioprotective drugs' biological availability, but also open a new route to develop neozoic radioprotective agents because some nanoparticles possess intrinsic radioprotective abilities. Therefore, considering these overwhelming superiorities, this review systematically summarizes the advances in healthy tissue radioprotection applications of multifunctional nanomaterials. Furthermore, this review also points out a perspective of nanomaterial designs for radioprotection applications and discusses the challenges and future outlooks of the nanomaterial-mediated radioprotection.