Nanomaterials promote the fast development of electrochemical MiRNA biosensors.

Cancer has become the leading cause of death worldwide. In recent years, molecular diagnosis has demonstrated great potential in the prediction and diagnosis of cancer. MicroRNAs (miRNAs) are short oligonucleotides that regulate gene expression and cell function and are considered ideal biomarkers for cancer detection, diagnosis, and patient prognosis. Therefore, the specific and sensitive detection of ultra-low quantities of miRNA is of great significance. MiRNA biosensors based on electrochemical technology have advantages of high sensitivity, low cost and fast response. Nanomaterials show great potential in miRNA electrochemical detection and promote the rapid development of electrochemical miRNA biosensors. Some methods and signal amplification strategies for miRNA detection in recent years are reviewed herein, followed by a discussion of the latest progress in electrochemical miRNA detection based on different types of nanomaterial. Future perspectives and challenges are also proposed for further exploration of nanomaterials to bring breakthroughs in electrochemical miRNA detection.

Cubic Na0.5Bi0.5TiO3 nanoperovskite significantly expands the application of sensitive immunosensor for the detection of carcinoembryonic antigen.

Nanosized sodium bismuth perovskite titanate (NBT) was synthesized and first used as the electrochemical immune sensing platform for the sensitive detection of carcinoembryonic antigen (CEA). Gold nanoparticles (Au NPs) grew on the surface of NBT through forming Au-N bond to obtain Au@NBT, and a label-free electrochemical immunosensor was proposed using Au@NBT as an immunosensing recognizer towards CEA. The well-ordered crystal structure of NBT was not changed at all after the modification of Au NPs outside, but significantly improved the conductivity, catalytic activity, and biocompatibility of the Au@NBT-modified electrode. The unique cubic crystal nanostructure of NBT offered a large active area for both Au NP modification and the subsequent immobilization of biomolecules over the electrode surface, triggering the effective generation of promising properties of the proposed Au@NBT-based electrochemical immunosensor. As expected, favorable detection performances were achieved using this immunosensor towards CEA detection, where a good linear relationship between the current response and CEA concentration was obtained in the concentration range 10 fg mL-1 to 100 ng mL-1 with a low detection limit (LOD) of 13.17 fg mL-1. Also, the significantly enhanced selectivity, and stability guaranteed the promising electrochemical properties of this immunosensor. Furthermore, the analysis of real serum samples verified the high feasibility of this new method in clinical CEA detection. This work opens a new window for the application of nanoperovskite in the early detection of CEA.

Hydrangea-like TiO2/Bi2MoO6 porous nanoflowers triggering highly sensitive electrochemical immunosensing to tumor marker.

Rapid and sensitive detection of carcinoembryonic antigen (CEA) is of great significance for cancer patients. Here, molybdenum (Mo) was doped into bismuth oxide (Bi2O3) by one-pot hydrothermal method forming porous tremella Bi2MoO6 nanocomposites with a larger specific surface area than the spherical structure. Then, a new kind of hydrangea-like TiO2/Bi2MoO6 porous nanoflowers (NFs) was prepared by doping titanium into Bi2MoO6, where titanium dioxide (TiO2) grew in situ on the surface of Bi2MoO6 nanoparticles (NPs). The hydrangea-like structure provides larger specific surface area, higher electron transfer ability and biocompatibility as well as more active sites conducive to the attachment of anti-carcinoembryonic antigen (anti-CEA) to TiO2/Bi2MoO6 NFs. A novel label-free electrochemical immunosensor was then constructed for the quantitative detection of CEA using TiO2/Bi2MoO6 NFs as sensing platform, showing a good linear relationship with CEA in the concentration range 1.0 pg/mL ~ 1.0 mg/mL and a detection limit of 0.125 pg/mL (S/N = 3). The results achieved with the designed immunosensor are comparable with many existing immunosensors used for the detection of CEA in real samples.

Recent advances in photothermal nanomaterials-mediated detection of circulating tumor cells.

Photothermal materials have shown great potential for cancer detection and treatment due to their excellent photothermal effects. Circulating tumor cells (CTCs) are tumor cells that are shed from the primary tumor into the blood and metastasize. In contrast to other tumor markers that are free in the blood, CTCs are a collective term for all types of tumor cells present in the peripheral blood, a source of tumor metastasis, and clear evidence of tumor presence. CTCs detection enables early detection, diagnosis and treatment of tumors, and plays an important role in cancer prevention and treatment. This review summarizes the application of various photothermal materials in CTC detection, including gold, carbon, molybdenum, phosphorus, etc. and describes the significance of CTC detection for early tumor diagnosis and tumor prognosis. Focus is also put on how various photothermal materials play their roles in CTCs detection, including CT, imaging and photoacoustic and therapeutic roles. The physicochemical properties, shapes, and photothermal properties of various photothermal materials are discussed to improve the detection sensitivity and efficiency and to reduce the damage to normal cells. These photothermal materials are capable of converting radiant light energy into thermal energy for highly-sensitive CTCs detection and improving their photothermal properties by various methods, and have achieved good results in various experiments. The use of photothermal materials for CTCs detection is becoming more and more widespread and can be of significant help in early cancer screening and later treatment.

Topochemical-like bandgap regulation engineering: A bismuth thiooxide nanocatalyst for breast cancer phototherapy.

The physical property tuning of nanomaterials is of great importance in energy, medicine, environment, catalysis, and other fields. Topochemical synthesis of nanomaterials can achieve precise control of material properties. Here, we synthesized a kind of element-doped bismuth-based nanomaterial (BOS) by topochemical-like synthesis and used it for the phototherapy of tumors. In this study, we employed bismuth fluoride nanoflowers as a template and fabricated element-doped bismuth oxide nanoflowers by reduction conditions. The product is consistent with the precursor in crystal structure and nanomorphology, realizing topochemical-like synthesis under mild conditions. BOS can generate reactive oxygen species, consume glutathione, and perform photothermal conversion under 730 nm light irradiation. In vitro and in vivo studies demonstrate that BOS could suppress tumor growth by inducing apoptosis and ferroptosis through phototherapy. Therefore, this study offers a general regulation method for tuning the physical properties of nanomaterials by using a topochemical-like synthesis strategy.

Virtual Screening-Based Study of Novel Anti-Cancer Drugs Targeting G-Quadruplex.

In order to develop new anti-cancer drugs more efficiently and reduce side effects based on active drug targets, the virtual drug screening was carried out through the target of G-quadruplexes and 23 hit compounds were, thus, screened out as potential anticancer drugs. Six classical G-quadruplex complexes were introduced as query molecules, and the three-dimensional similarity of molecules was calculated by shape feature similarity (SHAFTS) method so as to reduce the range of potential compounds. Afterwards, the molecular docking technology was utilized to perform the final screening followed by the exploration of the binding between each compound and four different structures of G-quadruplex. In order to verify the anticancer activity of the selected compounds, compounds 1, 6 and 7 were chosen to treat A549 cells in vitro, the lung cancer epithelial cells, for further exploring their anticancer activity. These three compounds were found to be of good characteristics in the treatment of cancer, which revealed the great application prospect of the virtual screening method in developing new drugs.

Pt Nanodot Inlaid Mesoporous NaBiOF Nanoblackberry for Remarkable Signal Amplification Toward Biomarker Detection.

A new ultrasensitive sandwich-type electrochemical immunosensor has been successfully constructed to quantitatively detect carcinoembryonic antigen (CEA) using blackberry-like mesoporous bismuth-based nanospheres NaBiOF (NBOF NSs) inlaid with Pt nanodots (NDs) (BiPt NSs) as the antibody capture and signal-amplifying probe. The growth of Pt NDs inside the holes of NBOF NSs formed the nanozyme inlay outside NBOF NSs, greatly increasing the specific surface area and exposure of the catalytic active sites by minimizing the particle size of the Pt to nanodot scale. Such a blackberry-shaped heterojunction structure of BiPt NSs was well-suited to antibody capture and improved the catalytic performance of BiPt NSs in reducing H2O2, amplifying the signal, and yielding highly sensitive detection of CEA. The use of Au nanoparticle-modified multi-walled carbon nanotubes (Au@MWCNTs) as the electrode substrates significantly enhanced the electron transfer behavior over the electrode surface, further increasing the conductivity and sensitivity of the immunosensor. Remarkably, good compatibility with human body fluid was achieved using the newly developed BiPt-based immunosensor resulting from the favorable biocompatibility and stability of both BiPt NSs and Au@MWCNTs. Benefiting from the double signal amplification strategy and the high biocompatibility, the immunosensor responded linearly to CEA in a wide range from 50 fg/mL to 100 ng/ml with an extremely low detection limit of 3.52 fg/mL (S/N = 3). The excellent detection properties of this new immunosensor were evidenced by the satisfactory selectivity, reproducibility, and stability obtained, as well as the reliable and precise determination  of CEA in actual human blood samples. This work provides a new strategy for the early clinical diagnosis of cancer. Novel blackberry-like mesoporous NaBiOF nanospheres with Pt nanodot inlay were successfully usedto construct a sandwich-type electrochemical immunosensor for the ultra-sensitive detection ofcarcinoembryonic antigen in human blood plasma based on a remarkable signal amplification strategy.

Potent saccharinate-containing palladium(II) complexes for sensitization to cancer therapy.

Palladium(II) (PdII) complexes are among the most promising anticancer compounds. Both 2`-benzoylpyridine thiosemicarbazone (BpT) and saccharinate (Sac) are efficient metal chelators with potent anticancer activity. To explore a more effective new anticancer drug, we synthesized a series of Sac and BpT-containing PdII complexes coordinated with thiosemicarbazone (TSC)-derived ligands, and characterized them through nuclear magnetic resonance (NMR), Fourier transformed infrared spectroscopy (FT-IR), elemental analysis, ultraviolet-visible spectroscopy (UV-Vis) and thermogravimetric analysis (TGA). Each target complex was composed of PdII, BpT, and one or two Sac molecules. Both the in vitro and in vivo anti-growth effects of those ligands and the obtained PdII complexes were investigated in the human lung adenocarcinoma cell lines A549 and Spc-A1. The coordination of PdII with the TSC-derivatives and Sac resulted in clearly greater anticancer activity than single ligands. These compounds were demonstrated to be safe for 293 T normal human kidney epithelial cells. The introduction of Sac into the TSC-derived PdII complex significantly enhanced anti-growth effects, and induced apoptosis of human lung cancer cells in vitro and in vivo in a dose dependent manner. Moreover, the PdII complex containing two Sac molecules showed the most promising therapeutic effects, thereby confirming that Sac increases the cancer therapeutic efficacy of PdII complexes and providing a new strategy for exploring anticancer drugs for potential clinical treatment.

Recent advances in stimuli-responsive nano-heterojunctions for tumor therapy.

Stimuli-responsive catalytic therapy based on nano-catalysts has attracted much attention in the field of biomedicine for tumor therapy, due to its excellent and unique properties. However, the complex tumor microenvironment conditions and the rapid charge recombination in the catalyst limit catalytic therapy's effectiveness and further development. Effective heterojunction nanomaterials are constructed to address these problems to improve catalytic performance. Specifically, on the one hand, the band gap of the material is adjusted through the heterojunction structure to promote the charge separation efficiency under exogenous stimulation and further improve the catalytic capacity. On the other hand, the construction of a heterojunction structure can not only preserve the function of the original catalyst but also achieve significantly enhanced synergistic therapy ability. This review summarized the construction and functions of stimuli-responsive heterojunction nanomaterials under the excitation of X-rays, visible-near infrared light, and ultrasound in recent years, and further introduces their application in cancer therapy. Hopefully, the summary of stimuli-responsive heterojunction nanomaterials' applications will help researchers promote the development of nanomaterials in cancer therapy.

Recent Development of Rhenium-Based Materials in the Application of Diagnosis and Tumor Therapy.

Rhenium (Re) is widely used in the diagnosis and treatment of cancer due to its unique physical and chemical properties. Re has more valence electrons in its outer shell, allowing it to exist in a variety of oxidation states and to form different geometric configurations with many different ligands. The luminescence properties, lipophilicity, and cytotoxicity of complexes can be adjusted by changing the ligand of Re. This article mainly reviews the development of radionuclide 188Re in radiotherapy and some innovative applications of Re as well as the different therapeutic approaches and imaging techniques used in cancer therapy. In addition, the current application and future challenges and opportunities of Re are also discussed.

Two Hawks with One Arrow: A Review on Bifunctional Scaffolds for Photothermal Therapy and Bone Regeneration.

Despite the significant improvement in the survival rate of cancer patients, the total cure of bone cancer is still a knotty clinical challenge. Traditional surgical resectionof bone tumors is less than satisfactory, which inevitably results in bone defects and the inevitable residual tumor cells. For the purpose of realizing minimal invasiveness and local curative effects, photothermal therapy (PTT) under the irradiation of near-infrared light has made extensive progress in ablating tumors, and various photothermal therapeutic agents (PTAs) for the treatment of bone tumors have thus been reported in the past few years, has and have tended to focus on osteogenic bio-scaffolds modified with PTAs in order to break through the limitation that PTT lacks, osteogenic capacity. These so-called bifunctional scaffolds simultaneously ablate bone tumors and generate new tissues at the bone defects. This review summarizes the recent application progress of various bifunctional scaffolds and puts forward some practical constraints and future perspectives on bifunctional scaffolds for tumor therapy and bone regeneration: two hawks with one arrow.

Efficient improvement in chemo/photothermal synergistic therapy against lung cancer using Bi@Au nano-acanthospheres.

Novel highly hydrophilic and biocompatible bismuth nanospheres with gold nanoparticles growing outside (Bi@Au nano-acanthospheres, Bi@Au NASs) were synthesized through a simple procedure, which demonstrated to be a promising photothermal agent owing to the ultrahigh photothermal conversion efficiency (η = 46.6 %). The as-prepared Bi@Au NASs showed excellent blood compatibility and fairly low cytotoxicity to human lung cancer A549 cells, as well as efficient photothermal ablation (PTA) therapy induced by a near-infrared laser. Under the 808 nm laser radiation, the tumour temperature could be elevated by ∼25 °C high enough to kill the cancer cells. Moreover, the anticancer drug doxorubicin hydrochloride (DOX) was successfully loaded in Bi@Au NASs with a loading content as high as 16.78 % and released under a pH sensitive release profile, a characteristic beneficial for intravenous delivery of DOX into cancer cells for chemotherapy. The presence of the Bi element enabled Bi@Au NASs to act as a favourable computed tomography (CT) contrast medium for CT imaging-guided tumour treatment. Compared with cancer treatment through either photothermal therapy or chemotherapy, the chemo-photothermal synergistic therapy using Bi@Au NASs as both a photothermal agent and a drug carrier has efficiently enhanced the in vitro and in vivo therapeutic effects in cancer treatment.

Enhanced catalytic amplification of mesoporous bismuth-gold nano-electrocatalyst triggering efficient capture of tumor marker.

A new sandwich-type electrochemical immunosensor for the sensitive detection of carcinoembryonic antigen (CEA) was originally developed using a unique bismuth (Bi)-gold (Au) nano-electrocatalyst triggering efficient capture of tumor marker, where the nano-electrocatalyst was obtained by implanting Au nanoparticles (Au NPs) inside the mesoporous NBiOF nanospheres (Au@NBOF NSs) for the purpose to marker secondary antibody (Ab2) and amplify the response signal through electrochemically catalyzing the reduction of hydrogen peroxide. The synergistic interaction between NBOF NSs and Au NPs endowed the as-received Au@NBOF nano-electrocatalyst with large electrocatalytic active surface area and powerful signal amplification function as upper sandwich layer to conjugate Ab2. The multi-walled carbon nanotubes sparkled with Au nanostars served as the lower sandwich layer to capture the primary antibody (Ab1), which enhanced the interfacial electron transport and the load capacity of Ab1 as a result of increasing the sensing response of the designed immunosensor based on the sandwich-type Ab1-CEA-Ab2 interaction. Such immunosensor proposed on the above double signal amplification strategy efficiently detected the target CEA in a wide concentration range from 100 fg mL-1 to 200 ng mL-1. The detection limit was as low as 9.57 fg mL-1 with excellent specificity and reproducibility. The satisfactory results in analyzing human serum samples indicate the potential application of this new immunosensor in early clinical diagnosis of cancer and the evaluation of treatment efficiency.

Rapid electrochemical detection of MiRNA-21 facilitated by the excellent catalytic ability of Pt@CeO2 nanospheres.

Pt@CeO2 nanospheres (NSs) were first synthesized by simply mixing Ce(NO3)3 and K2PtCl4 under the protection of pure argon at 70 °C for 1 h, which exhibited excellent catalytic ability toward hydrogen peroxide (H2O2). An electrochemical biosensor was successfully developed using Pt@CeO2 NSs as a capture probe for the ultra-sensitive and fast detection of miRNA-21, a new type of biomarker for disease diagnostics, especially for cancer. During the step-by-step construction process of the RNA sensor, Pt@CeO2 NSs were functionalized with streptavidin (SA) to obtain SA-Pt@CeO2 NSs through amide bonds. Gold nanoparticles (Au NPs) were electrodeposited on the surface of the glassy carbon electrode to improve the transmission capacity of electrons and provided Au atoms for fixing the thiolated capture probe (SH-CP) with a hairpin structure on the electrode via forming Au-S bonds. The target miRNA-21 specifically hybridized with SH-CP and opened the hairpin structure to form a rigid duplex so as to activate the biotin at the end of the capture probe. SA-Pt@CeO2 NSs were thus specially attached to the electrode surface through the biotin-streptavidin affinity interaction, finally leading to the significant signal amplification. The ultra-sensitive and rapid detection of miRNA-21 was finally realized as expected benefiting from the excellent catalytic ability of Pt@CeO2 NSs toward H2O2 in a wide linear concentration range from 10 fM to 1 nM with the detection limit as low as 1.41 fM. The results achieved with this new RNA sensor were quite satisfactory during the blood sample analysis.

Ultrasound-triggered reactive oxygen species effector nanoamplifier for enhanced combination therapy of mutant p53 tumors.

Reactive oxygen species (ROS) damage is a crucial method with which to inhibit tumor cell proliferation; however, tumor cells can reduce ROS damage by modulating multiple repair mechanisms, thus, reducing the efficacy of ROS damage in tumor therapy. In this study, we built an ultrasound-triggered ROS damage nanoamplifier using a synergistic strategy consisting of ROS damage and decreased tumor self-protection capability to enhance the treatment efficacy of mutant p53 tumors. A ROS damage nanoamplifier (PT@PTGA) was fabricated using amphiphilic polyglutamic acid (PTGA) to load with a sonosensitizer (protoporphyrin IX, PpIX) and an MTH1 inhibitor (TH287). Under ultrasonic excitation, PpIX catalyzes oxygen to produce singlet oxygen and release TH287 to inhibit MTH1 activity, thereby causing the accumulation of 8-oxo-dGTP, which enhances DNA damage and further induces cell apoptosis. In addition, TH287 allies with ROS to eliminate the mutated p53 protein in tumor cells, thus reducing the self-protective capacity of tumor cells. As a result, the "internal and external" aspects were combined to enhance sensitization for mutant p53 tumor therapy. The construction of a ROS nanoamplifier not only provides an effective strategy for the treatment of mutant p53 tumors but also supplies an integrated platform for tumor diagnosis and therapy.

Biodegradable Bismuth-Based Nano-Heterojunction for Enhanced Sonodynamic Oncotherapy through Charge Separation Engineering.

Sonodynamic therapy is a noninvasive treatment method that generates reactive oxygen species (ROS) triggered by ultrasound, to achieve oxidative damage to tumors. However, methods are required to improve the efficiency of ROS generation and achieve continuous oxidative damage. A ternary heterojunction sonosensitizer composed of Bi@BiO2-x @Bi2 S3 -PEG (BOS) to achieve thermal injury-assisted continuous sonodynamic therapy for tumors is prepared. The oxygen vacancy in BOS can capture hot electrons and promotes the separation of hot carriers on the bismuth surface. The local electric field induced by localized surface plasmon resonance also contributes to the rapid transfer of electrons. Therefore, BOS not only possesses the functions of each component but also exhibits higher catalytic activity to generate ROS. Meanwhile, BOS continuously consumes glutathione, which is conducive to its biodegradation and achieves continuous oxidative stress injury. In addition, the photothermal conversion of BOS under near-infrared irradiation helps to achieve thermal tumor damage and further relieves tumor hypoxia, thus amplifying the sonodynamic therapeutic efficacy. This process not only provides a strategy for thermal damage to amplify the efficacy of sonodynamic therapy, but also expands the application of bismuth-based heterojunction nanomaterials as sonosensitizers in sonodynamic therapy.

How Do Bismuth-Based Nanomaterials Function as Promising Theranostic Agents for the Tumor Diagnosis and Therapy?

The complexity of the tumor microenvironment and the diversity of tumors seriously affect the therapeutic effect, the focus, therefore, has gradually been shifted from monotherapy to combination therapy in clinical research in order to improve the curative effect. The synergistic enhancement interactions among multiple monotherapies majorly contribute to the birth of the multi-mode cooperative therapy, whose effect of the treatment is clearly stronger than that of any single therapy. In addition, the accurate diagnosis of the tumour location is also crucial to the treatment. Bismuth-based nanomaterials (NMs) hold great properties as promising theranostic platforms based on their many unique features that include low toxicity, excellent photothermal conversion efficiency as well as the high ability of X-ray computed tomography imaging and photoacoustic imaging. In this review, we will introduce briefly the main features of the tumor microenvironment first and its effect on the mechanism of nanomedicine actions and present the recent advances of bismuth-based NMs for diagnosis and photothermal therapy-based combined therapies using bismuth-based NMs are presented, which may provide a new way for overcoming drug resistance and hypoxia. In the end, further challenges and outlooks regarding this promising field are discussed accompanied with some design tips for bismuth- based NMs, hoping to provide researchers some inspiration to design safe and effective nanotherapeutic agents for clinical treatments of cancers.

Oxygen-Deficient BiOCl Combined with L-Buthionine-Sulfoximine Synergistically Suppresses Tumor Growth through Enhanced Singlet Oxygen Generation under Ultrasound Irradiation.

Excess generation of reactive oxygen species (ROS) based on sensitizers under ultrasound (US) excitation can cause the death of tumor cells via oxidative damage, but sonosensitizers are largely unexplored. Herein, oxygen-deficient black BiOCl (B-BiOCl) nanoplates (NPs) are reported, with post-treatment on conventional BiOCl by simple UV excitation, showing stronger singlet oxygen (1 O2 ) generation than commercial TiO2 nanoparticles and their derivatives under US irradiation. Moreover, L-buthionine-sulfoximine (BSO), a GSH biosynthesis inhibitor, is incorporated into B-BiOCl NPs. The authors find that BSO can be released owing to the degradation of B-BiOCl NPs in the presence of acid and GSH, which are overexpressed in tumors. The results show that BSO/B-BiOCl-PEG NPs have a multifunctional synergistic effect on improving ROS production. In particular, BiOCl has remarkable near-infrared light absorption after UV treatment and is good for photoacoustic imaging that can guide subsequent sonodynamic therapy. This work shows that just with a simple oxygen deficiency treatment, strong 1 O2 generation can be provided to a conventional material under US irradiation and, interestingly, this effect can be amplified by using a small inhibitor BSO, and this is clearly demonstrated in cell and mice experiments.

Tumor Microenvironment Modulation Platform Based on Composite Biodegradable Bismuth-Manganese Radiosensitizer for Inhibiting Radioresistant Hypoxic Tumors.

Solid tumors possess a unique internal environment with high-level thiols (mainly glutathione), over-expressed H2 O2 , and low oxygen partial pressure, which severely restrict the radiotherapy (RT) efficacy. To overcome the imperfections of RT alone, there is vital to design a multifunctional radiosensitizer that simultaneously achieves multimodal therapy and tumor microenvironment (TME) regulation. Bismuth (Bi)-based nanospheres are wrapped in the MnO2 layer to form core-shell-structured radiosensitizer (Bi@Mn) that can effectively load docetaxel (DTX). The solubility of Bi@Mn-DTX is further improved via folic acid-modified amphiphilic polyethylene glycol (PFA). Bi@Mn-DTX-PFA can specifically respond to the TME to realize multimodal therapy. Primarily, the outer MnO2 layer responds with H2 O2 and glutathione to release oxygen and generate •OH, thereby alleviating hypoxia and achieving chemodynamic therapy (CDT). Afterward, the strong coordination between Bi3+ and deprotonated thiol groups in glutathione allows the mesoporous Bi-containing core bonding with glutathione to form a water-soluble complex. These actions conduce Bi@Mn-DTX-PFA degradation, further releasing DTX to implement chemotherapy (CHT). In addition, the degradation in vivo and tumor enrichment of Bi@Mn-PFA are explored via T1 -weighted magnetic resonance and computed tomography imaging. The biodegradable composite Bi@Mn-DTX-PFA can simultaneously modulate the TME and achieve multimodal treatment (RT/CDT/CHT) for hypoxic tumors.

Biodegradable BiOCl platform for oxidative stress injury-enhanced chemodynamic/radiation therapy of hypoxic tumors.

Various physiological characteristics of the tumor microenvironment (TME), such as hypoxia, overexpression of glutathione (GSH) and hydrogen peroxide (H2O2), and mild acidity, can severely reduce the efficacy of many cancer therapies. Altering the redox balance of the TME and increasing oxidative stress can accordingly enhance the efficacy of tumor therapy. Herein, we developed a bismuth-based Cu2+-doped BiOCl nanotherapeutic platform, BCHN, able to self-supply H2O2 for TME-regulated chemodynamic therapy (CDT) combined with sensitized radiotherapy (RT). BCHN released H2O2 and consumed GSH to degrade the composite in the slightly acidic TME, and generated hydroxyl radicals (•OH) via a Fenton-like reaction catalyzed by copper ions, to achieve oxidative stress-enhanced CDT. The Fenton-like reaction also catalyzed H2O2 to produce O2 to relieve tumor hypoxia, and combined with the X-ray-blocking property of bismuth to realize TME-enhanced radiotherapy. Synergistic CDT/RT has previously been shown to effectively inhibit tumor cell proliferation and achieve effective tumor control. The current results demonstrated a highly efficient multifunctional bio-degradable nanoplatform for oncotherapy. STATEMENT OF SIGNIFICANCE: Tumor microenvironment-modulated synergy of radiotherapy and chemodynamic therapy is conducive to rapid tumor ablation. Based on this principle, we fabricated a biodegradable BiOCl-based nanocomposite, BCHN. By supplying H2O2, a Fenton-like reaction generated •OH and O2 catalyzed by copper ions, and consumed glutathione to biodegrade the composite. Overall, these actions increased tumor oxidative stress and realized the synergistic anti-tumor actions of chemodynamic therapy combined with bismuth-based sensitization radiotherapy. This strategy thus provides a unique approach to oncology therapy.