Glucose oxidase and ruthenium nanorods-embedded self-healing polyvinyl alcohol/polyethylene imine hydrogel for simultaneous photothermal/photodynamic/starvation therapy and skin reconstruction.

Tumor recurrence and wound healing represent significant burdens for tumor patients after the surgical removal of melanomas. Wound dressings with wound healing and anticancer therapeutic abilities could help to solve these issues. Thus, a hybrid hydrogel made of polyvinyl alcohol (PVA) and polyethylene imine (PEI) was prepared by cross-linking imine bond and boronic acid bond. This hydrogel was loaded with ruthenium nanorods (Ru NRs) and glucose oxidase (GOx) and named as nanocomposite hydrogel (Ru/GOx@Hydrogel), exhibiting remarkable photothermal/photodynamic/starvation antitumor therapy and wound repair abilities. Ru NRs are bifunctional phototherapeutic agents that simultaneously exhibit intrinsic photothermal and photodynamic functions. Three-dimensional composite hydrogel loaded with GOx can also consume glucose in the presence of O2 during tumor starvation therapy. Near-infrared (NIR) light-triggered hyperthermia can not only promote the consumption of glucose, but also facilitate the ablation of residual cancer cells. The antitumor effect of the Ru/GOx@Hydrogel resulted in significant improvements, compared to those observed with either phototherapy or starvation therapy alone. Additionally, the postoperative wound was substantially healed after treatment with Ru/GOx@Hydrogel and NIR irradiation. Therefore, the Ru/GOx@Hydrogel can be used as a multi-stimulus-responsive nanoplatform that could facilitate on-demand controlled drug release, and be used as a promising postoperative adjuvant in combination therapy.

Palladium nanoparticle based smart hydrogels for NIR light-triggered photothermal/photodynamic therapy and drug release with wound healing capability.

Tumor recurrence and wound repair are two major challenges following cancer surgical resection that can be addressed through precision nanomedicine. Herein, palladium nanoparticles (Pd NPs) with photothermal and photodynamic therapy (PTT/PDT) capacity were successfully synthesized. The Pd NPs were loaded with chemotherapeutic doxorubicin (DOX) to form hydrogels (Pd/DOX@hydrogel) as a smart anti-tumor platform. The hydrogels were composed of clinically approved agarose and chitosan, with excellent biocompatibility and wound healing ability. Pd/DOX@hydrogel can be used for both PTT and PDT with a synergistic effect to kill tumor cells. Additionally, the photothermal effect of Pd/DOX@hydrogel allowed the photo-triggered drug release of DOX. Therefore, Pd/DOX@hydrogel can be used for near-infrared (NIR)-triggered PTT and PDT as well as for photo-induced chemotherapy, efficiently inhibiting tumor growth. Furthermore, Pd/DOX@hydrogel can be used as a temporary biomimetic skin to block the invasion of foreign harmful substances, promote angiogenesis, and accelerate wound repair and new skin formation. Thus, the as-prepared smart Pd/DOX@hydrogel is expected to provide a feasible therapeutic solution following tumor resection.

Robust boron nanoplatform provokes potent tumoricidal activities via inhibiting heat shock protein.

Near-infrared (NIR)-light-triggered photothermal therapy (PTT) is a promising treatment for breast cancer. However, its therapeutic efficiency is often compromised due to the heat-induced up-regulation of heat shock proteins, which confer photothermal resistance. To solve this urgent problem, PEGylated two-dimensional boron nanosheets (B-PEG)-which allow both multimodal imaging and photothermal conversion-were loaded with gambogic acid (GA), which can inhibit heat shock protein 90 (Hsp90). Experimental findings indicated that this combination of B-PEG and GA could serve as an integrated drug delivery system for cancer diagnosis and treatment. It could be used to administer mild PTT as well as chemotherapy for breast cancer, provide improved anti-tumor effects, and reduce the toxicity of PTT, all while inhibiting breast cancer growth. This drug delivery system could offer a novel tool for administering chemotherapy combined with PTT while avoiding the adverse effects of traditional PTT.

Light-induced tumor theranostics based on chemical-exfoliated borophene.

Among 2D materials (Xenes) which are at the forefront of research activities, borophene, is an exciting new entry due to its uniquely varied optical, electronic, and chemical properties in many polymorphic forms with widely varying band gaps including the lightest 2D metallic phase. In this paper, we used a simple selective chemical etching to prepare borophene with a strong near IR light-induced photothermal effect. The photothermal efficiency is similar to plasmonic Au nanoparticles, with the added benefit of borophene being degradable due to electron deficiency of boron. We introduce this selective chemical etching process to obtain ultrathin and large borophene nanosheets (thickness of ~4 nm and lateral size up to ~600 nm) from the precursor of AlB2. We also report first-time observation of a selective Acid etching behavior showing HCl etching of Al to form a residual B lattice, while HF selectively etches B to yield an Al lattice. We demonstrate that through surface modification with polydopamine (PDA), a biocompatible smart delivery nanoplatform of B@PDA can respond to a tumor environment, exhibiting an enhanced cellular uptake efficiency. We demonstrate that borophene can be more suitable for safe photothermal theranostic of thick tumor using deep penetrating near IR light compared to gold nanoparticles which are not degradable, thus posing long-term toxicity concerns. With about 40 kinds of borides, we hope that our work will open door to more discoveries of this top-down selective etching approach for generating borophene structures with rich unexplored thermal, electronic, and optical properties for many other technological applications.

ClC-3 silencing mediates lysosomal acidification arrest and autophagy inhibition to sensitize chemo-photothermal therapy.

Protective autophagy can be activated by external stimuli such as chemotherapy (CT) and photothermal therapy (PTT), leading to tumour resistance. As a key subcellular for autophagy, lysosomal dysfunction is crucial for autophagy suppression. Furthermore, lysosomal drug sequestration enhances basic drug resistance such as doxorubicin (DOX), which is trapped away from its target site, namely, the nucleus. Moreover, most of nanodrug delivery systems are internalised to lysosome for degradation, which further leads to DOX resistance. Lysosome serves as an essential organelle in drug resistance mechanisms, whose acidification arrest provides a potential strategy to inhibit autophagy and lysosomal drug sequestration simultaneously. The chloride channel-3 (ClC-3) protein is known as an important Cl--H+ transporter to maintain lysosomal pH at low values of various human cells. Herein, a black phosphorus-based theranostic nanoplatform of BP-A-S@D is constructed, and HeLa cells are used as a model to verify the effect of ClC-3 on tumour lysosomal acidification and autophagy regulation. Consequently, ClC-3 silencing inhibits not only protective autophagy to sensitise chemo-photothermal therapy, but also DOX resistance by suppressing lysosomal acidification. Therefore, ClC-3 silencing could simultaneously inhibit autophagy and lysosomal drug sequestration to improve anti-tumour efficiency.

Biodistribution, degradability and clearance of 2D materials for their biomedical applications.

Two-dimensional (2D) materials have evolved to be a class of rapidly advancing chemical entities in the biomedical field. Nevertheless, potential side effects and safety concerns severely limit their clinical translation. After administration, 2D materials cross multiple biological barriers and are distributed throughout the body. Only the portion that accumulates at the diseased sites exerts a therapeutic effect, whereas those distributed elsewhere may cause damage to healthy tissues and interference to normal physiological function of various organs. To achieve maximum therapeutic efficacy and minimum adverse effects simultaneously, the delivery of 2D materials must be targeted at diseased sites to reach therapeutic concentrations, and the materials must possess sufficient degradation and clearance rates to avoid long-term toxicity. Therefore, it is essential to understand the biodistribution and destiny of 2D materials in vivo. In this review, first, we provide a comprehensive picture of the strategies that are currently adopted for regulating the in vivo fate of 2D materials, including modulations of their size, surface properties, composition, and external stimuli. Second, we systematically review the biodistribution, degradation, and metabolism of several newly emerged 2D materials. Finally, we also discuss the development opportunities of 2D materials in the biomedical field and the challenges to be addressed.

A CRISPR/Cas12a-empowered surface plasmon resonance platform for rapid and specific diagnosis of the Omicron variant of SARS-CoV-2.

The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus, and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On the other hand, several concerning SARS-CoV-2 variants, including Omicron, are required to be identified as soon as the samples are identified as 'positive'. Unfortunately, a traditional PCR test does not allow their specific identification. Herein, for the first time, we have developed MOPCS (Methodologies of Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance (SPR) with the 'gene scissors' clustered regularly interspaced short palindromic repeat (CRISPR) technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants. MOPCS is a low-cost, CRISPR/Cas12a-system-empowered SPR gene-detecting platform that can analyze viral RNA, without the need for amplification, within 38 min from sample input to results output, and achieve a limit of detection of 15 fM. MOPCS achieves a highly sensitive analysis of SARS-CoV-2, and mutations appear in variants B.1.617.2 (Delta), B.1.1.529 (Omicron) and BA.1 (a subtype of Omicron). This platform was also used to analyze some recently collected patient samples from a local outbreak in China, identified by the Centers for Disease Control and Prevention. This innovative CRISPR-empowered SPR platform will further contribute to the fast, sensitive and accurate detection of target nucleic acid sequences with single-base mutations.

CRISPR-Cas12a-Empowered Electrochemical Biosensor for Rapid and Ultrasensitive Detection of SARS-CoV-2 Delta Variant.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gold standard method for the diagnosis of SARS-CoV-2 depends on quantitative reverse transcription-polymerase chain reaction till now, which is time-consuming and requires expensive instrumentation, and the confirmation of variants relies on further sequencing techniques. Herein, we first proposed a robust technique-methodology of electrochemical CRISPR sensing with the advantages of rapid, highly sensitivity and specificity for the detection of SARS-CoV-2 variant. To enhance the sensing capability, gold electrodes are uniformly decorated with electro-deposited gold nanoparticles. Using DNA template identical to SARS-CoV-2 Delta spike gene sequence as model, our biosensor exhibits excellent analytical detection limit (50 fM) and high linearity (R2 = 0.987) over six orders of magnitude dynamic range from 100 fM to 10 nM without any nucleic-acid-amplification assays. The detection can be completed within 1 h with high stability and specificity which benefits from the CRISPR-Cas system. Furthermore, based on the wireless micro-electrochemical platform, the proposed biosensor reveals promising application ability in point-of-care testing.

Recent Advances in 2D Layered Phosphorous Compounds.

2D layered phosphorous compounds (2D LPCs) have led to explosion of research interest in recent years. With the diversity of valence states of phosphorus, 2D LPCs exist in various material types and possess many novel physical and chemical properties. These properties, including widely adjustable range of bandgap, diverse electronic properties covering metal, semimetal, semiconductor and insulator, together with inherent magnetism and ferroelectricity at atomic level, render 2D LPCs greatly promising in the applications of electronics, spintronics, broad-spectrum optoelectronics, high-performance catalysts, and energy storage, etc. In this review, the recently research progress of 2D LPCs are presented in detail. First, the 2D LPCs are classified according to their elemental composition and the corresponding crystal structures are introduced, followed by their preparation methods. Then, the novel properties are summarized and the potential applications are discussed in detail. Finally, the conclusion and perspective of the promising 2D LPCs are discussed on the foundation of the latest research progress.

Strategic Design of Intelligent-Responsive Nanogel Carriers for Cancer Therapy.

Owing to the distinctive constituents of tumor tissue from those healthy organs, nanomedicine strategies show significant potentials in smart drug delivery. Nowadays, stimuli-responsive nanogels are playing increasingly important roles in the application of cancer therapy because of their sensitivity to various internal or external physicochemical stimuli, which exhibit site-specific and markedly enhanced drug release. Besides, nanogels are promising as drug carriers because of their porous structures, good biocompatibility, large surface area, and excellent capability with drugs. Taking advantage of multiresponsiveness, recent years have witnessed the rapid evolution of stimulus-responsive nanogels from monoresponsive to multiresponsive systems; however, there lacks a comprehensive review summarizing these reports. In this Review, we discuss the properties, synthesis, and characterization of nanogels. Moreover, tumor microenvironment and corresponding designing strategies for stimuli-response nanogels, both exogenous (temperature, magnetic field, light) and endogenous (pH, biomolecular, redox, ROS, pressure, hypoxia) are summarized on the basis of the recent advances in multistimuli-responsive nanogel systems. Nanogel and two-dimensional material composites show excellent performance in the field of constructing multistimulus-responsive nanoparticles and precise intelligent drug release integrated system for multimodal cancer diagnosis and therapy. Finally, potential progresses and suggestions are provided for the further design of hybrid nanogels based on emerging two-dimensional materials.

2D materials for bone therapy.

Due to their prominent physicochemical properties, 2D materials are broadly applied in biomedicine. Currently, 2D materials have achieved great success in treating many diseases such as cancer and tissue engineering as well as bone therapy. Based on their different characteristics, 2D materials could function in various ways in different bone diseases. Herein, the application of 2D materials in bone tissue engineering, joint lubrication, infection of orthopedic implants, bone tumors, and osteoarthritis are firstly reviewed comprehensively together. Meanwhile, different mechanisms by which 2D materials function in each disease reviewed below are also reviewed in detail, which in turn reveals the versatile functions and application of 2D materials. At last, the outlook on how to further broaden applications of 2D materials in bone therapies based on their excellent properties is also discussed.

Recent advances in the development of nanomedicines for the treatment of ischemic stroke.

Ischemic stroke is still a serious threat to human life and health, but there are few therapeutic options available to treat stroke because of limited blood-brain penetration. The development of nanotechnology may overcome some of the problems related to traditional drug development. In this review, we focus on the potential applications of nanotechnology in stroke. First, we will discuss the main molecular pathological mechanisms of ischemic stroke to develop a targeted strategy. Second, considering the important role of the blood-brain barrier in stroke treatment, we also delve mechanisms by which the blood-brain barrier protects the brain, and the reasons why the therapeutics must pass through the blood-brain barrier to achieve efficacy. Lastly, we provide a comprehensive review related to the application of nanomaterials to treat stroke, including liposomes, polymers, metal nanoparticles, carbon nanotubes, graphene, black phosphorus, hydrogels and dendrimers. To conclude, we will summarize the challenges and future prospects of nanomedicine-based stroke treatments.

Smart nano-micro platforms for ophthalmological applications: The state-of-the-art and future perspectives.

Smart nano-micro platforms have been extensively applied for diverse biomedical applications, mostly focusing on cancer therapy. In comparison with conventional nanotechnology, the smart nano-micro matrix can exhibit specific response to exogenous or endogenous triggers, and thus can achieve multiple functions e.g. site-specific drug delivery, bio-imaging and detection of bio-molecules. These intriguing techniques have expanded into ophthalmology in recent years, yet few works have been summarized in this field. In this work, we provide the state-of-the-art of diverse nano-micro platforms based on both the conventional materials (e.g. natural or synthetic polymers, lipid nanomaterials, metal and metal oxide nanoparticles) and emerging nanomaterials (e.g. up-conversion nanoparticles, quantum dots and carbon materials) in ophthalmology, with some smart nano/micro platformers highlighted. The common ocular diseases studied in the field of nano-micro systems are firstly introduced, and their therapeutic method and the related drawback in clinic treatment are presented. The recent progress of different materials for diverse ocular applications is then demonstrated, with the representative nano- and micro-systems highlighted in detail. At last, an in-depth discussion on the clinical translation challenges faced in this field and the future direction are provided. This review would allow the researchers to design more smart nanomedicines in a more rational manner for specific ophthalmology applications.

2D Nanomaterials for Tissue Engineering and Regenerative Nanomedicines: Recent Advances and Future Challenges.

Regenerative medicine has become one of the hottest research topics in medical science that provides a promising way for repairing tissue defects in the human body. Due to their excellent physicochemical properties, the application of 2D nanomaterials in regenerative medicine has gradually developed and has been attracting a wide range of research interests in recent years. In particular, graphene and its derivatives, black phosphorus, and transition metal dichalcogenides are applied in all the aspects of tissue engineering to replace or restore tissues. This review focuses on the latest advances in the application of 2D-nanomaterial-based hydrogels, nanosheets, or scaffolds that are engineered to repair skin, bone, and cartilage tissues. Reviews on other applications, including cardiac muscle regeneration, skeletal muscle repair, nerve regeneration, brain disease treatment, and spinal cord healing are also provided. The challenges and prospects of applications of 2D nanomaterials in regenerative medicine are discussed.

Prodrug-Loaded Zirconium Carbide Nanosheets as a Novel Biophotonic Nanoplatform for Effective Treatment of Cancer.

Conventional chemotherapy and photothermal therapy (PTT) face many major challenges, including systemic toxicity, low bioavailability, ineffective tissue penetration, chemotherapy/hyperthermia-induced inflammation, and tumor angiogenesis. A versatile nanomedicine offers an exciting opportunity to circumvent the abovementioned limitations for their successful translation into clinical practice. Here, a promising biophotonic nanoplatform is developed based on the zirconium carbide (ZrC) nanosheet as a deep PTT-photosensitizer and on-demand designed anticancer prodrug SN38-Nif, which is released and activated by photothermia and tumor-overexpressed esterase. In vitro and in vivo experimental evidence shows the potent anticancer effects of the integrated ZrC@prodrug biophotonic nanoplatform by specifically targeting malignant cells, chemotherapy/hyperthermia-induced tumor inflammation, and angiogenesis. In mouse models, the ZrC@prodrug system markedly inhibits tumor recurrence, metastasis, inflammation and angiogenesis. The findings unravel a promising biophotonic strategy for precision treatment of cancer.

Rapid prediction of drug inhibition under heat stress: single-photon imaging combined with a convolutional neural network.

A method of predicting cellular drug inhibition due to heat stress is presented. Black phosphorus nanosheets are used as photothermal agents to induce stress granule formation in tumor cells. The addition of different drugs induces different thermal stress responses. The features of single-photon images are automatically extracted and analyzed by a convolutional neural network algorithm for classification and recognition, with a maximum accuracy rate of 94.52%. Unlike traditional visual discrimination, this method realizes intelligent recognition without human intervention, providing a new model for computer-aided diagnosis with greater objectivity.

Liquid-phase exfoliation of black sesame to create a nanoplatform for in vitro photoluminescence and photothermal therapy.

Aim: The present study aims to apply the facile liquid-phase exfoliation (LPE) strategy to fabricate 2D organic materials and thus to broaden the family of biocompatible and multifunctional 2D materials. Materials & methods: 2D material-organic melanin and cellulose nanosheets were synthesized from black sesame hull using LPE. Photoluminescence and photothermal properties of the nanosheets were assessed, as well as stability and cell killing ability. Results: The prepared 2D nanoplatform exhibited broad and multiple photoluminescent emission bands. It also demonstrated efficient photothermal cancer therapy with excellent biocompatibility. Conclusion: The present study could open an avenue in exfoliating organic materials using the LPE strategy. This could make the fabrication of multifunctional 2D organic materials more efficient and broaden the family of biocompatible 2D nanomaterials.

Immunogenic exosome-encapsulated black phosphorus nanoparticles as an effective anticancer photo-nanovaccine.

Tumor vaccines are a promising form of cancer immunotherapy, but difficulties such as neo-antigen identification, activation of immune cells, and tumor infiltration prevent their clinical breakthrough. Interestingly, nanotechnology-based photothermal therapy (PTT) has great potential to overcome these barriers. Previous studies have shown that serum exosomes (hEX) from hyperthermia-treated tumor-bearing mice displayed an array of patient-specific tumor-associated antigens (TAAs), and strong immunoregulatory abilities in promoting dendritic cell (DC) differentiation and maturation. Here, we developed a tumor vaccine (hEX@BP) by encapsulating black phosphorus quantum dots (BPQDs) with exosomes (hEX) against a murine subcutaneous lung cancer model. In comparison with BPQDs alone (BP), hEX@BP demonstrated better long-term PTT performance, greater elevation of tumor temperature and tumor targeting efficacy in vivo. Vaccination with hEX@BP in combination with PTT further demonstrated an outstanding therapeutic efficacy against established lung cancer, and promoted the infiltration of T lymphocytes into the tumor tissue. Our findings demonstrated that hEX@BP might be an innovative cancer photo-nanovaccine that offers effective immuno-PTT against cancers.

Two-Dimensional Black Arsenic Phosphorus for Ultrafast Photonics in Near- and Mid-Infrared Regimes.

Black arsenic phosphorus (b-AsP), as one kind of novel two-dimensional (2D) materials, bridges the band gap between black phosphorus and graphene. Thanks to its great advantages, including high carrier mobility, excellent in-plane anisotropy, and broad tunability band gap, b-AsP has aroused great interest in fields of photonics and photoelectronics. In this paper, ultrathin 2D b-AsP nanomaterials were fabricated by the liquid-phase exfoliation method, and their strong broadband linear and nonlinear absorptions were characterized by ultraviolet-visible-infrared and Z-scan technology. The experimental determination of the nonlinear absorption coefficient and low saturation intensity of b-AsP were -0.23 cm/GW and 3.336 GW/cm2, respectively. Based on density functional theory, the partial charge density and band structure at the conduction band minimum and valence band maximum were calculated, which further proves the excellent optical properties of 2D b-AsP. By first using 2D b-AsP as a novel saturable absorber in both erbium-doped and thulium-doped fiber lasers, mode-locked soliton pulses can stably operate at 1.5 and 2 µm. The laser pulses generated by 2D b-AsP possess higher stability to resist self-splitting than those generated by other 2D material-based mode-lockers. These experimental results highlight that 2D b-AsP has great application potential as a novel optical material in ultrafast photonics from near- to mid-infrared regimes.

Recent advances of two-dimensional materials in smart drug delivery nano-systems.

Smart drug delivery nano-systems show significant changes in their physical or chemical properties in response to slight change in environmental physical and/or chemical signals, and further releasing drugs adjusted to the progression of the disease at the right target and rate intelligently. Two-dimensional materials possess dramatic status extend all over various scientific and technological disciplines by reason of their exceptional unique properties in application of smart drug delivery nano-systems. In this review, we summarized current progress to highlight various kinds of two-dimensional materials drug carriers which are widely explored in smart drug delivery systems as well as classification of stimuli responsive two-dimensional materials and the advantages and disadvantages of their applications. Consequently, we anticipate that this review might inspire the development of new two-dimensional materials with smart drug delivery systems, and deepen researchers' understanding of smart nano-carries based on two-dimensional materials.