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The aggregation of hydrophobic photosensitizers limits the therapeutic effect of photodynamic therapy (PDT). Improving the hydrophilicity of photosensitizers can reduce their aggregation for enhancing PDT. Herein, a nanosystem (TPFcNP) is developed by a hydrophobic photosensitizer 5,10,15,20-tetrakis(4-methacryloyloxyphenyl)porphyrin (TMPP) containing multiple carbon-carbon double bonds and a ferrocene-containing amphiphilic block copolymer (PEG-b-PMAEFc), which catalyzes hydrogen peroxide (H2O2) to produce hydroxyl radicals (•OH) in a tumor microenvironment by the Fenton reaction. The •OH could catalyze the addition reaction between the carbon-carbon double bonds of TMPP and overexpressed water-soluble glutathione (GSH) in tumor cells, which greatly improves the hydrophilicity of photosensitizers and reduces their aggregation. Experiments in vitro and in vivo have proved that this strategy significantly enhances the therapeutic efficacy of PDT. Catalyzing intracellular reactions in situ by making use of the tumor microenvironment will open up a new opportunity to solve the aggregation of materials in the tumor for cancer treatment.

Summary Calcium overload, characterized by an abnormal cytoplasm accumulation of free calcium ions (Ca2+), is a widely recognized cause of damage in numerous cell types and even of cell death. This undesirable destructive process can become a new tool applicable to cancer treatment. Herein, on the basis of the unique biological effect of Ca2+, we demonstrate a highly efficient strategy for tumor therapy by utilizing pH-sensitive sodium-hyaluronate-modified calcium peroxide nanoparticles (SH-CaO2 NPs). These NPs create an artificial calcium overloading stress in tumor cells, which is responsible for cell death. Notably, the killing effect is not limited to tumor types or hypoxic cells, and normal cells are more tolerant of the adverse influence of NPs than tumor cells. The Ca2+ enrichment also increases the likelihood of tumor calcification, which could contribute to in vivo tumor inhibition and facilitate medical imaging to monitor the treatment efficacy.

The ongoing SARS-CoV-2 pandemic highlights the importance of materials science in providing tools and technologies for antiviral research and treatment development. In this Review, we discuss previous efforts in materials science in developing imaging systems and microfluidic devices for the in-depth and real-time investigation of viral structures and transmission, as well as material platforms for the detection of viruses and the delivery of antiviral drugs and vaccines. We highlight the contribution of materials science to the manufacturing of personal protective equipment and to the design of simple, accurate and low-cost virus-detection devices. We then investigate future possibilities of materials science in antiviral research and treatment development, examining the role of materials in antiviral-drug design, including the importance of synthetic material platforms for organoids and organs-on-a-chip, in drug delivery and vaccination, and for the production of medical equipment. Materials-science-based technologies not only contribute to the ongoing SARS-CoV-2 research efforts but can also provide platforms and tools for the understanding, protection, detection and treatment of future viral diseases., Materials science provides tools and technologies for the protection against viral infections, as well as for the understanding, diagnosis, treatment and prevention of viral diseases. This Review discusses present and future directions in antiviral materials-science research, with a focus on COVID-19.

Interest in cancer immunotherapy has rapidly risen since it offers many advantages over traditional approaches, such as high efficiency and prevention of metastasis. Efforts have primarily focused on two major strategies for regulating the body's antitumor immune response mechanisms: “enhanced immunotherapy” that aims to amplify the immune activation, and “normalized immunotherapy” that corrects the defective immune mechanism in the tumor immune microenvironments (TIMEs), which returns to the normal immune trajectory. However, due to the complexity and heterogeneity of the TIMEs, and lack of visualization research on the immunotherapy process, cancer immunotherapy has not been widely used in clinical setting. Recently, through the design and modification of nanomaterials, intelligent TIME-responsive nanoplatforms were developed from which encouraging results in many aspects of immunotherapy have been achieved. In this mini review, the status of designed nanomaterials for nanoplatform-based immune regulation of TIMEs has been emphasized, particularly with respect to the aforementioned approaches. It is envisaged that future prospects will focus on a combination of multiple immunotherapies for more efficient cancer inhibition and elimination.

Clay-based nanomaterials, especially 2:1 aluminosilicates such as vermiculite, biotite, and illite, have demonstrated great potential in various fields. However, their characteristic sandwiched structures and the lack of effective methods to exfoliate two-dimensional (2D) functional core layers (FCLs) greatly limit their future applications. Herein, we present a universal wet-chemical exfoliation method based on alkali etching that can intelligently “capture” the ultrathin and biocompatible FCLs (MgO and Fe2O3) sandwiched between two identical tetrahedral layers (SiO2 and Al2O3) from vermiculite. Without the sandwich structures that shielded their active sites, the obtained FCL nanosheets (NSs) exhibit a tunable and appropriate electron band structure (with the bandgap decreased from 2.0 eV to 1.4 eV), a conductive band that increased from −0.4 eV to −0.6 eV, and excellent light response characteristics. The great properties of 2D FCL NSs endow them with exciting potential in diverse applications including energy, photocatalysis, and biomedical engineering. This study specifically highlights their application in cancer theranostics as an example, potentially serving as a prelude to future extensive studies of 2D FCL NSs., Clay-based nanomaterials are of wide interest but problems extracting the 2D functional core layers have limited potential applications. Here, the authors report on the wet exfoliation of vermiculite by alkali etching to obtain the core layers and explore the application of the materials in cancer theranostics.

The key bottleneck problem of chemodynamic therapy (CDT) is that the efficiency depends heavily on an acidic chemical environment. However, there is a sufficient blood supply on the surface of solid tumours, resulting in neutral-pH surface regions, strongly reducing the effectiveness of CDT. In this study, chelating complex ferrous-cysteine–phosphotungstate nanoparticles (FcPWNPs) are synthesized to serve as new CDT nanoagents that break through the limitation of a neutral pH, ensuring CDT efficiencies at both an acidic and neutral pH. The CDT efficiency is increased by introducing cysteine and phosphotungstate, which form an Fe chelating complex to inhibit the formation of inert Fe(OH)x, and accelerate electron transfer between ferric and ferrous ions, respectively. Due to this ferrous chelating strategy and associated electron transfer property, the FcPWNPs can destroy cancer cells from the neutral-pH tumour surface to the acidic interior, thus realizing a complete CDT cancer therapy.

The common existence of hypoxia in solid tumors has been heavily researched because it renders tumors more resistant to most standard therapeutic methods, such as radiotherapy (RT), chemotherapy, and photodynamic therapy (PDT), and is associated with a more malignant phenotype and poor survival in patients with tumors. The development of hypoxia modulation methods for advanced therapeutic activity is therefore of great interest but remains a considerable challenge. Since the significant development of nanotechnology and nanomedicine, functionalized nanomaterials can be exploited as adjuvant "drugs" for these oxygen-dependent standard therapies or as hypoxia initiators for advanced new therapies to solid tumors. In this Account, we summarize our recent studies on the design and synthesis of nanomaterials with a set of desired chemistry benefits achievable by modulating hypoxia, suggesting a valid therapeutic option for tumors. The investigated strategies can be categorized into three groups: The first strategy is based on countering hypoxia. Considering that O

X-ray-induced photodynamic therapy (X-PDT) has high depth of penetration and has considerable potential for applications in cancer therapy. Scintillators and heavy metals have been adopted to absorb X-rays and transmit the energy to photosensitizers. However, the low efficiency of converting X-rays to reactive oxygen species (ROS) presents a challenge for the use of X-PDT to cure cancer. In this study, a new method based on LiLuF4:Ce@SiO2@Ag3PO4@Pt(IV) nanoparticles (LAPNP) is presented that could be used to enhance the curative effects of X-PDT. To make full use of the fluorescence produced by nanoscintillators (LiLuF4:Ce), a cisplatin prodrug Pt(IV) was utilized as a sacrificial electron acceptor to increase the yield of hydroxyl radicals (·OH) by increasing the separation of electrons and holes in photosensitizers (Ag3PO4). Additionally, cisplatin is produced upon the acceptance of electrons by Pt(IV) and further enhances the damage caused by ·OH. Via two-step amplification, the potential of LAPNP to enhance the effects of X-PDT has been demonstrated.

The "partial matching" between upconversion nanoparticle (UCNP) emission and absorption by photosensitizers (PSs) often leads to a theoretically reduced therapeutic efficiency in UC-based photodynamic therapy (PDT) strategies in which the chosen PSs have limited capabilities and are unable to utilize all the near-infrared-upconverted light. In this study, needle-like SnWO4 nanocrystals (SWs) with a broad UV-vis absorption region were synthesized to solve the problem. After covalent conjugation with UCNPs, all the UCNP-emitted light was effectively absorbed by SWs, triggering the type-I PDT process to activate ROS maxima. The unique nanostructure of the as-formed UCNP-SnWO4 nanohybrids (USWs) also enhanced the receiving light intensities of SW, which further boosted the antitumor efficacy. Meanwhile, the strong X-ray attenuation capacity of both tungsten and tin elements qualified the USWs as excellent radio-sensitizers for radiotherapy (RT) enhancement, which played a complementary role with PDT treatment because PDT-mediated induction arrested the cells in the G0-G1 cell cycle phase, and RT was more damaging toward cells in the G2/M phase. The remarkably enhanced UC-PDT/RT efficiency of USWs was next validated in vitro and in vivo, and the combined NIR light and ionizing irradiation treatment completely suppressed tumor growth, revealing its great potential as an efficient anticancer therapeutic agent against solid tumors.

Two-photon (TP) absorption nanomaterials are highly desirable for deep-tissue clinical diagnostics and orthotopic disease treatment. Here, a well-designed core/shell nanostructure was successfully synthesized with a ZnTPyP self-assembly nanocrystal (ZSN) inner core coated by a homogeneous TiO2 layer outside (ZSN–TO). The ZSN is a good photosemiconductor, showing both one-photon (OP) and TP absorption properties for red fluorescence emission and electron–hole pair generation; TiO2 with good biocompatibility acts as the electron acceptor, which can transfer photoelectron from ZSN to TiO2 for highly effective electron–hole separation, favoring the production of long-life superoxide anion (O2•–) by electrons and oxygen and strong oxidizing hydroxyl radical (•OH) by holes and surrounding H2O. Once pretreated with ZSN–TO, the simultaneous OP-405 nm or TP-800 nm laser stimulation and fluorescent imaging of reactive oxygen species (ROS) showed dynamical and continuous generation of ROS in HeLa cells, with cytotox...

Photothermal therapy (PTT) has been attracting much attention because of its high efficiency and ease of use. Currently deployed PTT, however, shows two main deficiencies: limited penetration depth and interference from heat shock proteins (HSPs). Here we describe a specific application of a pyroelectric material, specifically SnSe-polyvinylpyrrolidone (SnSe-PVP) nanorods, for tumor photoacoustic imaging and PTT, accompanied by pyroelectric dynamic therapy (PEDT), utilizing near-infrared-II (NIR-II) light as the excitation trigger. Moreover, we used PEDT to generate reactive oxygen species (ROS) from SnSe-PVP nanorods and to have the ROS attack HSPs and cancer cells during heating and cooling. This work revealed a high potential for the application of pyroelectric materials in biomedicine, especially for PTT with PEDT via NIR-II light stimulation.

Gd3+-based contrast agents (CAs) are the most prevailing and widely used for enhanced magnetic resonance imaging (MRI). Numbers of approaches have been developed to regulate the key parameters in order to obtain high-relaxivity CAs, according to the classic Solomon–Bloembergen–Morgen theory. Herein, a method of controlling oxygen vacancies in inorganic nanosized CAs has been developed for largely accelerated proton relaxation to obtain a high r1 value. Such a strategy is verified on oxygen-deficient PEG-NaxGdWO3 nanorods, which exhibit a remarkable r1 value up to 80 mM–1 s–1 (at 0.7 T) and a high r1 value of 32.1 mM–1 s–1 on a clinical 3.0 T scanner, offering an excellent blood pool MRI performance at a low dose. Meanwhile, free electrons and/or oxygen-vacancy-induced small polarons can endow PEG-NaxGdWO3 nanorods with significant photothermal conversion for MRI-guided photothermal therapy.

At present, tumor diagnosis is performed using common procedures, which are slow, costly, and still presenting difficulties in diagnosing tumors at their early stage. Tumor therapeutic methods also mainly rely on large-scale equipment or non-intelligent treatment approaches. Thus, an early and accurate tumor diagnosis and personalized treatment may represent the best treatment option for a successful result, and the efforts in finding them are still in progress and mainly focusing on non-destructive, integrated, and multiple technologies. These objectives can be achieved with the development of advanced devices and smart technology that represent the topic of the current investigations. Therefore, this review summarizes the progress in tumor diagnosis and therapy and briefly explains the advantages and disadvantages of the described microdevices, finally proposing advanced micro smart devices as the future development trend for tumor diagnosis and therapy.

The conversion of bulk water to confined water in biological tissues has been proposed to benefit the treatments of diseases. However, regulating the states of water in vivo is still a challenge. Herein, we constructed nanocatalysts (BiOCl) containing abundant superficial vacancies to confine water in situ and investigated the potential utilization in cancer radiotherapy. Vacancies absorbed bulk water, transformed its structure and converted it to confined water. Enhanced reactivity of confined water increased the efficiency of water radiolysis and the yield of hydroxyl radicals (·OH) from radiation exposure. The results validated the feasibility of water-confinement-based radiosensitization strategy. These findings not only provide a method of constructing confined water in vivo, but also present the potentials of confined water for biological applications.

The clinical applications of polymer-based nanomedicines have been restricted by their complicated synthesis processes, biosafety issues, and uncontrollable drug loading. In this study, we developed a peptide-like polydrug for cancer chemotherapy using the FDA-approved drug melphalan via a simple one-step synthesis strategy. The prepared poly (melphalan) (PMP)-PEG was characterized through standard methods and formulated into sub-100 nm nanoparticles using the nanoprecipitation method. The poly (melphalan)-PEG nanoparticles (PMP NPs) showed controllable drug loading (up to 70 wt%) with high stability in buffers. In vitro cell viability studies showed good cell uptake behavior and high cytotoxicity of the PMP-NPs compared to Evomela controls (a commercial and clinical melphalan formulation). For in vivo mouse models tests, the PMP-NPs could accumulate in the tumor sites for ≥ 1 week and effectively inhibited tumor growth with minimal side-effects. This peptide synthesis strategy and a melphalan based polydrug nanoplatform may be promising for new drug development and effective cancer therapy.

Graphical abstract, Highlights • Detailed role that nanotechnology can play in addressing this pandemic. • Using FDA-approved nanomaterials for drug/vaccine delivery, including further exploration of the inhalation pathway. • Introducing promising nanomaterials currently in clinical trials for drug/vaccine delivery. • Designing novel biocompatible nanomaterials to combat the virus via interfering in its life cycle. • Promoting the utilization of nanomaterials in pneumonia treatment., In just a few months, SARS-CoV-2 and the disease it causes, COVID-19, created a worldwide pandemic. Virologists, biologists, pharmacists, materials scientists, and clinicians are collaborating to develop efficient treatment strategies. Overall, in addition to the use of clinical equipment to assist patient rehabilitation, antiviral drugs and vaccines are the areas of greatest focus. Given the physical size of SARS-CoV-2 and the vaccine delivery platforms currently in clinical trials, the relevance of nanotechnology is clear, and previous antiviral research using nanomaterials also supports this connection. Herein we briefly summarize current representative strategies regarding nanomaterials in antiviral research. We focus specifically on SARS-CoV-2 and the detailed role that nanotechnology can play in addressing this pandemic, including i) using FDA-approved nanomaterials for drug/vaccine delivery, including further exploration of the inhalation pathway; ii) introducing promising nanomaterials currently in clinical trials for drug/vaccine delivery; iii) designing novel biocompatible nanomaterials to combat the virus via interfering in its life cycle; and iv) promoting the utilization of nanomaterials in pneumonia treatment.

As an effective treatment approach, photo-therapeutic has great potential in treating various diseases, but this light-activated strategy suffers from the major shortcoming of low tissue penetration depth. Low-intensity ultrasound features with non-invasive and high tissue-penetrating ability have been widely used in clinical diagnostic, which can effectively overcome the major limitation of light. Sonodynamic therapy (SDT) is a novel noninvasive therapeutic modality that involves a combination of low-intensity ultrasound and sonosensitizers. Combining nanotechnology with SDT can effectively augment the SDT efficiency and may essentially reverse the disadvantages of traditional SDT, paving an avenue for more efficient and safer therapeutic options. In this review, we highlight the recent advances of SDT in nanoscience in terms of its possible mechanisms of action, applications against various diseases and synergistic effects of SDT in combination with other therapeutic modalities. Moreover, potential limitations and future prospects are also discussed.

Excess electrons play important roles for the construction of superficial active sites on nanocatalysts. However, providing excess electrons to nanocatalysts in vivo is still a challenge, which limits the applications of nanocatalysts in biomedicine. Herein, auger electrons (AEs) emitted from radionuclide 125 (125I) are used in situ to construct active sites in a nanocatalyst (TiO2) and the application of this method is further extended to cancer catalytic internal radiotherapy (CIRT). The obtained 125I‐TiO2 nanoparticles first construct superficial Ti3+ active sites via the reaction between Ti4+ and AEs. Then Ti3+ stretches and weakens the O—H bond of the absorbed H2O, thus enhancing the radiolysis of H2O molecules and generating hydroxyl radicals (•OH). All in vitro and in vivo results demonstrate a good CIRT performance. These findings will broaden the application of radionuclides and introduce new perspectives to nanomedicine., A simple and highly efficient catalytic internal radiotherapy (CIRT) is developed by 125I‐labeled TiO2 nanoparticles. Auger electrons from 125I react with Ti4+ in TiO2 and construct superficial active sites of Ti3+. The generated Ti3+ decreases the energy barriers of H2O and contributes to the generation of •OH upon γ‐rays irradiation, thus enhancing the antitumor effect of IRT.

The stability and safety of magnetic resonance imaging (MRI) contrast agents (CAs) are crucial for accurate diagnosis and real-time monitor of tumor development. Paramagnetic Mn2+ as nonlanthanide metal ion has been widely studied for use in T1-MRI CAs, but unfortunately, Mn2+ can be oxidized by H2O2 in tumor to nonparamagnetic Mn4+ via a Fenton-like reaction. The concurrent loss of paramagnetism and production of toxic hydroxyl radical ( OH) go against the basic requirment of CAs, thus restricting the further development of Mn2+-based CAs. Based on the different standard potential of W6+/W5+ (~0.26 V) and Mn4+/Mn2+ (~1.2 V), a “cathodic protection” strategy was exploited in Mn2+-doped NaxWO3 nanorods (NaxMnWO3), with W5+ as the sacrificial anode and Mn2+ as the protected cathode, to protect Mn2+ from oxidation in tumor for stable MR contrast performance, as well as repress its Fenton-like reaction activity for good biosafety. Moreover, the tungsten bronze crystal structure endows NaxMnWO3 with excellent near-infrared (NIR)-photothermal properties for effective tumor hyperthermia, without effect from the changed oxidation state of W. This “cathodic protection” strategy offers a new method for the development of reliable and hypotoxic biomaterials for stable imaging and therapeutic applications in clinic.

Hypoxia, as an inevitable characteristic of solid tumors, has been regarded as a noticeably causative factor to therapeutic resistance and metastatic variants. Exploring novel theranostics to realize the accurate diagnosis of hypoxia and the simultaneous implementation of effective therapy is a promising prospect for the successful treatment of tumors. In the present study, we designed and synthesized a multifunctional rattle-structured nanotheranostic, with the inner core coated by hollow mesoporous silica for chemical drug Doxorubicin (DOX) storage and hypoxia-sensitive MnO2 enrichment. In various acidic micro-environments caused by hypoxia, MnO2 nanosheets could be degraded into manganese ions (Mn2+), which were chelated by the modified Tetraxetanum (DOTA) ligands for real-time T1-magnetic resonance imaging (T1-MRI), with on-demand DOX release to realize both normoxia and hypoxia-sensitive chemotherapy by overcoming hypoxia. Nanotheranostics integrating hypoxia-driven T1-MRI with synergetic chemotherapy have tremendous potential in the intelligent diagnosis, personalized treatment and excellent prognosis of solid tumors in the future.

Several decades of research have identified the specific tumor microenvironment (TME) to develop promising nanotheranostics, such as pH-sensitive imaging, acidity-sensitive starving therapy, and hydrogen peroxide-activated chemotherapy, etc. Herein, a novel TME-mediated nanoplatform employing antiferromagnetic pyrite nanocubes is presented, exploiting the intratumoral, overproduced peroxide for self-enhanced magnetic resonance imaging (MRI) and photothermal therapy (PTT)/chemodynamic therapy (CDT). Through the activation of excessive peroxide in the tumor microenvironment, pyrite can lead to in situ surface oxidation and generate hydroxyl radicals to kill tumor cells (i.e., CDT). The increase of the valence state of surface Fe significantly promotes the performance of MRI accompanied by CDT. Furthermore, the localized heat by photothermal treatment can accelerate the intratumoral Fenton process, enabling a synergetic PTT/CDT. To our best knowledge, this is the first study to use the TME-response valence-variable strategy based on pyrite for developing a synergetic nanotheranostic, which will open up a new dimension for the design of other TME-based anticancer strategies.

Biodegradable nanoprodrugs, inheriting the antitumor effects of chemotherapy drugs and overcoming the inevitable drawback of side effects on normal tissues, hold promise as next-generation cancer therapy candidates. Biodegradable nanoprodrugs of transferrin-modified MgO2 nanosheets are developed to selectively deliver reactive oxygen species to cancer cells for molecular dynamic therapy strategy. The nanosheets favor the acidic and low catalase activity tumor microenvironment to react with proton and release nontoxic Mg2+ . This reaction simultaneously produces abundant H2 O2 to induce cell death and damage the structure of transferrin to release Fe3+ , which will react with H2 O2 to produce highly toxic ·OH to kill tumor cells.

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T1 MR-based nanoprobes, NaGdF4 -TAT, as molecular probes with high longitudinal relaxivity (8.93 mm-1 s-1 ) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF4 -TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 107 labeled T-cells by T1 -weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF4 -TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas.