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This research proposes the one-pot preparation of polydopamine (PDA) decorated mesoporoussilica nanoparticle (PMSN) for the thermal and tumor micro-environment (TME) responsive colorectal tumor therapy. The pores of PMSN were used for the Fe

The development of efficient strategies for in vivo stimuli-responsive cancer treatment and personalized biomedicine is a great challenge. To overcome the critical issues and limitations of traditional protocols using acoustic droplet vaporization and optical droplet vaporization in stimuli-responsive tumor treatment, we herein report a new strategy, magnetic droplet vaporization (MDV), based on nanobiotechnology, for efficient magnetic field-responsive cancer theranostics. Perfluorohexane (PFH)-encapsulated superparamagnetic hollow iron oxide nanoparticles with a high magnetic-thermal energy transfer capability quickly respond to an external alternating current (a.c.) magnetic field to produce thermal energy and raise the temperature of the surrounding tumor tissue. The encapsulated PFH, with a desirable boiling point of ~56°C, can be vaporized to enhance the performance of ultrasound imaging of tumors, as systematically demonstrated both in vitro and in vivo. The magnetic–thermal energy transfer further ablated and removed tumors in mice tumor xenograft models. This unique MDV principle with high versatility and performance is expected to broaden the biomedical applications of nanotechnology and promote clinical translations of intelligent diagnostic and therapeutic modalities, especially for battling cancer.

Excessive emission of CO2 leads to global warming, and CO2 reduction is a promising method to utilize excessive emission. Light-driven reactions, including photoelectrochemical (PEC) and photochemi...

Overproduced hydrogen sulfide (H

Electrocatalytic CO2 conversion into value-added fuels to form a sustainable recycling system is desirable but is still confronted with a problem about the lack of highly active electrocatalysts. Herein, novel AlxBiyOz nanorods were synthesized by a facile hydrothermal method for the electrochemical CO2 reduction reaction (CO2RR). The obtained sample exhibits high electrocatalytic activity for CO2 conversion with a faradaic efficiency (FE) of above 90% to formate under a wide potential window from −0.79 V to −1.29 V vs. RHE. Particularly, a FE to formate of up to 97.5% can be achieved at −1.19 V vs. RHE. Furthermore, it shows great stability during the 10 h electrolysis at −0.79 V vs. RHE. It is believed that the introduction of Al species could modulate the electronic configuration of Bi2O3, together with the enlarged surface area and exposed (2 0 1) crystal plane contributing to the enhanced adsorption and activation capability of CO2, which could mainly account for the high CO2RR performance.

The current reported photosensitizers generally show a decreased reactive oxygen species (ROS) generation property under hypoxia conditions, which is the main reason for the clinical failure of photodynamic therapy (PDT) in treatment of solid tumors. Herein, for the first time, hypoxia-induced photogenic radicals by eosin Y (Eos) were reported for efficient phototherapy of hypoxic tumors. More importantly, Eos shows a higher ROS and radical production efficiency under hypoxia conditions than under normoxia conditions. The photogenic radicals were captured by electron paramagnetic resonance and further verified by ROS and radical probe. Introducing CoCl

Converting CO2 into value-added chemicals or fuels by electrochemical CO2 reduction reaction (CO2 RR) has aroused great interest, whereas designing highly active and selective electrocatalysts is still a challenge. Herein, a novel kind of electrochemical catalyst composed with SnO2 and organic carbon (OC), named as SnO2 /OC, was facilely constructed for CO2 RR. The obtained SnO2 /OC exhibits both high faradaic efficiency for formate (∼75 %) and carbon products (∼95 %) as well as excellent stability. High surface area with hierarchically porous structure and the homogeneous formation of Sn-O-C linkages in SnO2 /OC jointly promote the adsorption and activation of CO2 , as well as fast transport of reactants and products.

Metal-organic framework (MOF)-based drug delivery nanosystems with both precise drug release and multidrug codelivery capabilities have emerged as promising candidates for cancer treatment. However, challenges are posed by the limited number of suitable payload types, uncontrollable drug leakage, and lack of chemical groups for postmodification. To overcome those challenges, we developed a core-shell nanocomposite composed of zeolitic imidazolate framework-90 (ZIF-90) coated with spermine-modified acetalated dextran (SAD) by a facile microfluidics-based nanoprecipitation method. This nanocomposite could serve as a multidrug storage reservoir for the loading of two drugs with distinct properties, where the hydrophilic doxorubicin (DOX) was coordinately attached to the ZIF-90 framework, and hydrophobic photosensitizer IR780 was loaded into the SAD shell, enabling the combination therapy of photodynamic treatment with chemotherapy. Meanwhile, equipping ZIF-90 with a SAD shell not only substantially improved the pH-responsive drug release of ZIF-90 but also enabled the postformation conjugation of ZIF-90 with hyaluronic acid for specific CD44 recognition, thereby facilitating precise drug delivery to CD44-overexpressed tumor. Such a simple microfluidics-based strategy can efficiently overcome the limitations of solely MOF-based DDSs and greatly extend the flexibility of MOF biomedical applications.

Despite advances in photodynamic therapy (PDT) for treating superficial tumor, the prospect of this monotherapy remains challenges in the context of systemic phototoxicity and poor efficacy. In this work, a physiologically self-degradable microneedle (MN)-assisted platform is developed for combining PDT and immunotherapy via controlled co-delivery of photosensitizer (PS) and checkpoint inhibitor anti-CTLA4 antibody (aCTLA4), which generates synergistic reinforcement outcome while reducing side effects. MN is composed of biocompatible hyaluronic acid integrated with the pH-sensitive dextran nanoparticles, which is fabricated to simultaneously encapsulate hydrophobic (Zinc Phthalocyanine) and hydrophilic agents (aCTLA4) via a double emulsion method. This co-loading carrier can aggregate effectively around topical tumor by microneedle-assisted transdermal delivery. In vivo studies using 4T1 mouse models, PDT firstly exerts its effect to killing tumor and triggers the immune responses, subsequently, facilitating the immunotherapy with immune checkpoint inhibitor (aCTLA4). The possible mechanism and systemic effects of the combined therapy are investigated, which demonstrate that this co-administration platform can be a promising tool for focal cancer treatment.

Chemodynamic therapy (CDT) that utilizes endogenous hydrogen peroxide (H2O2) to produce reactive oxygen species (ROS) to kill cancer cells has shown a promising strategy for malignant tumor treatment. Nevertheless, limited H2O2 levels in the tumor microenvironment often compromise the therapeutic benefits of CDT, leading to cancer recurrence and metastasis. Herein, a second near-infrared (NIR-II) photothermal Fenton nanocatalyst (PFN) was developed for activatable magnetic resonance imaging (MRI)-guided synergetic photothermal therapy (PTT) and CDT of pancreatic carcinoma. Such a PFN consists of manganese dioxide (MnO2), copper sulfide (CuS), and human serum albumin (HSA), which serve as the activatable imaging contrast agent, the NIR-II photothermal agent and Fenton catalyst, and the stabilizer, respectively. The acidic tumor microenvironment increased the relaxivity of PFN by 2.1-fold, allowing for improved imaging performance and monitoring of nanoparticle accumulation in tumors. Under NIR-II laser irradiation at 1064 nm, PFN generates local heat, which not only permits PTT but also enhances the nanocatalyst-mediated Fenton-like reaction. As such, PFN exerts a synergetic action to completely ablate xenografted tumor models in living animals, while the sole CDT fails to do so. This study thus provides an NIR-II photothermal nanocatalyst for potential treatment of deep-seated tumors.

Magnetite (Fe3O4) nanoparticles have been extensively used in noninvasive cancer treatment, for example, magnetic hyperthermia (MH) and chemodynamic therapy (CDT). However, how to achieve a highly efficient MH-CDT synergistic therapy based only on a single component of Fe3O4 still remains a challenge. Herein, hollow Fe3O4 mesocrystals (MCs) are constructed via a modified solvothermal method. Owing to the distinctive magnetic property of the mesocrystalline structure, Fe3O4 MCs show excellent magnetothermal conversion efficiency with a specific absorption rate of 722 w g-1 at a Fe concentration of 0.6 mg mL-1, much higher than that of Fe3O4 polycrystals (PCs). Moreover, Fe3O4 MCs also exhibit higher peroxidase-like activity than Fe3O4 PCs, which may be ascribed to the higher ratio of Fe2+/Fe3+ and more oxygen defects in the Fe3O4 MCs. Detailed in vivo results confirm that Fe3O4 MCs can instantly initiate CDT by producing the detrimental •OH, and such boosted reactive oxygen levels not only induces cell apoptosis but also reduces the expression of heat shock proteins, thus enabling low-temperature-mediated MH. More importantly, the in situ rising temperature resulted from MH in turn facilitates CDT, thus achieving a self-augmented synergistic effect between MH and CDT.

Clinical manifestations of tumors indicate that malignant phenotypes developing in the hypoxic microenvironment lead to resistance to cancer treatment, rendering chemotherapy, radiotherapy, and photodynamic therapy less sensitive and effective in patients with tumor. Visualizing the oxygen level in the tumor environment has garnered much attention due to its implications in precision tumor therapy. Following the rapid development of biomaterials in nanotechnology, various nanomaterials have been designed to visualize the oxygen levels in tumors. Here, we review recent research on detecting oxygen levels in solid tumors for tumor hypoxia imaging. To monitor the hypoxic level of tumors, two main strategies were investigated: directly detecting oxygen levels in tumors and monitoring the hypoxia-assisted reduced microenvironment. We believe that hypoxia as a tumor-specific microenvironment can be a breakthrough in the clinical treatment of tumors.

Mesenchymal stem cells (MSCs) transplantation is a promising approach for pulmonary fibrosis (PF), however it is impeded by several persistent challenges, including the lack of long-term tracking, low retention, and poor survival of MSCs, as well as the low labeling efficiency of nanoprobes. Herein, a cobalt protoporphyrin IX (CoPP) aggregation-induced strategy is applied to develop a multifunctional nano-self-assembly (ASCP) by combining gold nanoparticle (AuNPs), superparamagnetic iron oxide nanoparticles (SPIONs), and CoPP through a facile solvent evaporation-driven approach. Since no additional carrier materials are employed during the synthesis, high loading efficiency of active ingredients and excellent biocompatibility are achieved. Additionally, facile modification of the ASCPs with bicyclo[6.1.0]nonyne (BCN) groups (named as ASCP-BCN) enables them to effectively label MSCs through bioorthogonal chemistry. The obtained ASCP-BCN could not only help to track MSCs with AuNP-based computed tomography (CT) imaging, but also achieve an SPIONs-assisted magnetic field based improvement in the MSCs retention in lungs as well as promoted the survival of MSCs

The ubiquitous mineralization of calcium phosphate (CaP) facilitates biological organisms to produce hierarchically structured minerals. The coordination number and strength of Ca2+ ions with phosphate species, oxygen-containing additives, and solvent molecules played a crucial role in tuning nucleation processes and surface stability of CaP under the simulated body fluid (SBF) or aqueous solutions upon the addition of oligomeric lactic acid (LACn, n=1, 8) and changing pH values. As revealed by ab initio molecular dynamics (AIMD), density functional theory (DFT), and molecular dynamics (MD) simulations as well as high-throughput experimentation (HTE), the binding of LAC molecules with Ca2+ ions and phosphate species could stabilize both pre-nucleation clusters and brushite (DCPD, CaHPO4·2H2O) surface through intermolecular electrostatic and hydrogen bonding interactions. When the concentration of Ca2+ ions ([Ca2+]) is very low, the amount of the formed precipitation decreased with the addition of LAC based on UV-Vis spectroscopic analysis due to the reduced chance for the LAC capped Ca2+ ions to coordinate with phosphates and the increased solubility in acid solution. With the increasing [Ca2+] concentration, the kinetically stable DCPD precipitation was obtained with high Ca2+ coordination number and low surface energy. Morphologies of DCPD precipitation are in plate, needle, or rod, depending on the initial pH values that tuned by adding NH3·H2O, HCl, or CH3COOH. The prepared samples at pH ≈ 7.4 with different Ca/P ratios exhibited negative zeta potential values, which were correlated with the surface electrostatic potential distributions and potential biological applications.

The immunosuppressive tumor microenvironment (TME) always causes poor antitumor immune efficacy, prone to relapse and metastasis. Herein, novel poly(vinylpyrrolidone) (PVP) modified BiFeO

The impermeable barriers of solid tumors restrict the co-delivery of protein-based drugs and chemotherapeutics for cancer treatment. Therefore, we developed a ZIF-DOX/RA@DG nanosystem that encapsulates ribonuclease A (RA) and doxorubicin (DOX) in a zeolitic imidazolate framework (ZIF-8) core, with a dextran-based coating (DG). The nanosystem exhibits dual-responsiveness due to γ-glutamyl transpeptidase-activatable cationization and acidic microenvironment-triggered degradation. The DG-coating process was achieved using a microfluidic approach, which stabilized the polymer responsiveness, ZIF-8-based structure, and bioactivity of the encapsulated therapeutics. In vivo results confirmed that the nanosystem could co-deliver RA and DOX to deep impermeable lesions with a synergistic anticancer therapeutic effects. Such a multi-drug delivery system based on an intelligent-responsive design and a microfluidics-assisted synthesis strategy shows great clinical prospects.

Nickel-iron layered double hydroxide (NiFe LDH) is a promising oxygen evolution reaction (OER) electrocatalyst under alkaline conditions. Much research has been performed to understand the structure-activity relationship of NiFe LDH under OER conditions. However, the specific role of the Fe species remains unclear and under debate. Herein, based on DFT calculations, it was discovered that the edge Fe sites show higher activity towards OER than either the edge Ni sites or lattice sites. Therefore, a facile acid-etching method was proposed to controllably induce the formation of edge Fe sites in NiFe LDH, and the obtained sample exhibited higher OER activity. X-ray absorption near edge structure and extended X-ray absorption fine structure analyses further revealed that the interaction of the edge Fe species with Ni is believed to contribute to the enhancement of the OER performance. This work provides a new understanding of the structure-activity relationship in NiFe LDH and offers a facile method for the design of efficient electrocatalysts in an alkaline environment.

Excellent imaging performance and good biocompatibility of contrast agents are considered as prerequisites for accurate tumor diagnosis. In this study, a novel imaging nanoprobe with actively targeting performance based on ultrasmall paramagnetic iron oxide (USPIO) nanoparticles was constructed by a facile cation exchange strategy followed by conjugation with transferrin (Tf). The stable gadolinium (Gd3+) chelation endows the nanoparticles (NPs) with a low value of r2/r1 (1.28) and a relatively high r1 value of 3.2 mM−1 s−1, enabling their use for T1-weighted positive magnetic resonance (MR) imaging. This constructed transferrin modified gadolinium-iron chelate nanoprobe, named as TUG, shows high biocompatibility within a given dose range. More importantly, compared with clinically used Gd-based small molecule contrast agents, the obtained TUG can be more engulfed by breast cancer cells, showing much enhanced T1-weighted positive MR imaging in both subcutaneous and orthotopic tumor models of breast cancer. This novel nanoprobe holds great promise to be utilized as a targeting contrast agent with high efficacy for T1-weighted positive MR imaging.

Much attention has been paid to the fabrication of two-dimensional (2D) nanomaterials as therapeutics for nanomedicine in recent years owing to their special physicochemical characteristics. These fascinating physicochemical properties alongside their diverse biomedical applications drive us to give a review of the present endeavors of interest in these 2D nanomaterials. In this review, the up-to-date research advances of the preparation, biocompatibility and biodegradation behaviors of 2D nanomaterials including transition-metal dichalcogenides (TMDs), transition metal oxides (TMOs), black phosphorus (BP) nanosheets, metal-organic frameworks (MOFs), 2D boron (B), boron nitride (BN), layered double hydroxides (LDHs), 2D nanoscale metals, and other kinds of 2D nanomaterials are introduced. The in vitro and in vivo bio-compatibility, including their degradation assessments from the aspects of a redox reaction, enzymes, pH, and the cell environment, etc., of the above categories of 2D nanomaterials are discussed in detail. Finally, the prospects and challenges of the development of 2D nanomaterials aiming for biomedical applications are summarized.

Rationale: Ferritin with unique hollow cavity is an emerging protein-based nanoplatform for anticancer-drug delivery, but the in vivo chemotherapeutic effectiveness is still unsatisfactory with such a monotherapy modality, which is urgently in need of improvement. Methods: Here a novel ferritin nanotheranostic with anticancer-drug doxorubicin encapsulated into its hollow interior and nanoradiosensitizer bismuth sulfide nanocrystals inlayed onto its polypeptide shell was synthesized for combinational therapeutic benefits. The formation mechanism of bismuth sulfide nanocrystals based on ferritin has been analyzed. The in vitro and in vivo treatment effects were carried out on HeLa cancer cells and tumor-bearing mice, respectively. The biocompatibility and excretion of the ferritin nanotheranostic have also been evaluated to guarantee their biosafety. Results: The polypeptide shell of ferritin provides nucleation sites for the bismuth sulfide nanocrystals through coordination interaction, and simultaneously inhibits the further growth of bismuth sulfide nanocrystals, rendering the bismuth sulfide nanocrystals like rivets inlaying onto the polypeptide firmly, which can not only strengthen the architectural stability of ferritin to prevent drug burst leakage during systemic circulation, but also act as excellent computed tomography contrast agents and nanoradiosensitizers for in vivo imaging-guided cancer combinational treatments. Conclusions: The design concept of inlaying bismuth sulfide nanocrystals onto the polypeptide shell of doxorubicin-encapsulated ferritin significantly inhibits the tumor growth and simultaneously further broadens the application of ferritin in nanomedicine.

Mineralization of calcium phosphate (CaP) is ubiquitous in nature, which can facilitate biological organisms produce hierarchically structured minerals. The influences of the addition of oligomeric lactic acid (LACn, n=1, 8) and changing pH values on nucleation processes of CaP under the simulated body fluid (SBF) solution or aqueous solution were revealed by using ab initio molecular dynamics (AIMD) and molecular dynamics (MD) simulations. Through increasing pH value, the coordination between differently protonated phosphate species and Ca2+ ions could be tuned from the monodentate (η1) to the coexisting monodentate and bidentate (η2) modes. The carboxyl and hydroxyl groups of LAC molecules are capable of forming multiple interactions such as proton transfer, electrostatic interaction, and intermolecular hydrogen bonding with phosphate species and Ca2+ ions on both pre-nucleation clusters and hydroxyapatite (HA) surfaces. The high-throughput experimentations (HTE) with factors of the adding LAC, changing Ca/P ratios (1.25 ~ 2.50), using different solutions demonstrated that the UV-Vis absorbance values decreased with addition of LAC, indicating the inhibition of the nucleation process of CaP. At the physiological pH of 7.4, the CaP samples with different Ca/P ratios (1.50, 1.67 and 2.00) exhibited negative zeta potential values, which were correlated with the surface electrostatic potential distributions and potential biological applications. The precipitation was CaHPO4·2H2O (DCPD) in neutral condition at the early stage of nucleation process. Understanding the effects of different pH and Ca/P values on the nucleation process and interfacial interaction between LAC additive and the nanocluster is helpful to guide the rational design of biocompatible materials.

For melanoma with high lethality and metastasis rate, traditional therapy has limited effects; local photothermal therapy (PTT) synergetic with immune therapy for cancer treatment can perhaps improve the situation. However, because of the natural existence of the tumor matrix barrier, the penetration depth of drugs and immune cells often dampens the efficacy of cancer treatment. Herein, we report an innovative synergetic PTT and immune therapy through dissolving microneedles for the codelivery of the hyaluronidase-modified semiconductor polymer nanoparticles containing poly(cyclopentadithiophene-alt-benzothiadiazole) and immune adjuvant polyinosinic-polycytidylic acid (PIC). Benefiting from the dissolution of an extracellular matrix of hyaluronidase, the semiconductor polymer nanoparticles and PIC penetrate the tumor deeply, under synergetic therapy with PTT, activating the immune cells and enhancing the T-cell immune response for inhibition of tumor growth and metastasis. This study provides a promising platform for effective melanoma treatment and a novel strategy to overcome the stromal barrier.

Scaffold hopping is a widely used strategy for drug design towards kinase inhibitors. In current study, we proposed a fragment-based deep learning strategy for scaffold hopping towards the conserved hinge binding motif of kinase inhibitors in a large scale.

Excellent imaging performance and good biocompatibility of contrast agents are considered as prerequisites for accurate tumor diagnosis. In this study, a novel imaging nanoprobe with actively targeting performance based on ultrasmall paramagnetic iron oxide (USPIO) nanoparticles was constructed by a facile cation exchange strategy followed by conjugation with transferrin (Tf). The stable gadolinium (Gd3+) chelation endows the nanoparticles (NPs) with a low value of r2/r1 (1.28) and a relatively high r1 value of 3.2 mM-1 s-1, enabling their use for T1-weighted positive magnetic resonance (MR) imaging. This constructed transferrin modified gadolinium-iron chelate nanoprobe, named as TUG, shows high biocompatibility within a given dose range. More importantly, compared with clinically used Gd-based small molecule contrast agents, the obtained TUG can be more engulfed by breast cancer cells, showing much enhanced T1-weighted positive MR imaging in both subcutaneous and orthotopic tumor models of breast cancer. This novel nanoprobe holds great promise to be utilized as a targeting contrast agent with high efficacy for T1-weighted positive MR imaging.