This report presents nanoparticles composed of a liquid gallium core with a reduced graphene oxide (RGO) shell (Ga@RGO) of tunable thickness. The particles are produced by a simple, one-pot nanoprobe sonication method. The high near-infrared absorption of RGO results in a photothermal energy conversion of light to heat of 42.4%. This efficient photothermal conversion, combined with the large intrinsic thermal expansion coefficient of liquid gallium, allows the particles to be used for photoacoustic imaging, that is, conversion of light into vibrations that are useful for imaging. The Ga@RGO results in fivefold and twofold enhancement in photoacoustic signals compared with bare gallium nanoparticles and gold nanorods (a commonly used photoacoustic contrast agent), respectively. A theoretical model further reveals the intrinsic factors that affect the photothermal and photoacoustic performance of Ga@RGO. These core-shell Ga@RGO nanoparticles not only can serve as photoacoustic imaging contrast agents but also pave a new way to rationally design liquid metal-based nanomaterials with specific multi-functionality for biomedical applications.

Synthesis of Liquid Gallium@Reduced Graphene Oxide Core-Shell Nanoparticles with Enhanced Photoacoustic and Photothermal Performance.

Nanozyme-based cascade reaction has emerged as an effective strategy for disease treatment because of its high efficiency and low side effects. Herein, a new and highly active two-dimensional Pd-Ru nanozyme is prepared and then integrated with uricase and red blood cell (RBC) membrane to fabricate a tandem nanoreactor, Pd-Ru/Uricase@RBC, for hyperuricemia treatment. The designed Pd-Ru/Uricase@RBC nanoreactor displayed not only good stability against extreme pH, temperature and proteolytic degradation, but also long circulation half-life and excellent safety. The nanoreactor can effectively degrade UA by uricase to allantoin and H2 O2 and remove H2 O2 by using Pd-Ru nanosheets (NSs) with the catalase (CAT)-like activity. More importantly, the finally produced O2 from H2 O2 decomposition can in turn facilitate the catalytic oxidation of UA, as the degradation of UA is an O2 consumption process. By integrating the high-efficiency enzymatic activity, long circulation capability, and good biocompatibility, the designed Pd-Ru/Uricase@RBC can effectively and safely treat hyperuricemia without side effects. The study affords a new alternative for the exploration of clinical treatment of hyperuricemia.

A Novel Cascade Nanoreactor Integrating Two-Dimensional Pd-Ru Nanozyme, Uricase and Red Blood Cell Membrane for Highly Efficient Hyperuricemia Treatment.

Theranostic nanoplatforms combining various diagnostic and therapeutic units together have attracted increasing attention over the past few decades. Owing to the merits of non-invasiveness, spatiotemporal controllability, high treatment efficacy and low normal-tissue damage, photothermal therapy (PTT) especially near-infrared-II (NIR-II, 1000–1700 nm) light-triggered PTT becomes one of the most popular therapeutic modalities. Interestingly, photothermal agents (PTAs) used for PTT often have an intrinsic photoacoustic (PA) imaging function, which means that PTAs alone can serve as all-in-one theranostic nanoplatforms. With the rapid development of nanomedicine, a single photothermal agent can be endowed with desirable photothermal conversion efficiency (PCE) in the NIR-II biowindow as well as possessing diverse treatment capabilities. This review summarizes the most recent advances of inorganic PTAs for imaging-guided NIR-II PTT, PTT/photodynamic therapy (PDT), PTT/chemodynamic therapy (CDT), PTT/radiotherapy (RT), PTT/sonodynamic therapy (SDT), PTT/PDT/CDT and PTT/SDT/immunotherapy. Potential obstacles and perspectives for future research and clinical translation of such novel nanotheranostics are also discussed. 

All-in-one inorganic nanoagents for near-infrared-II photothermal-based cancer theranostics

Skin wound healing often contains a series of dynamic and complex physiological healing processes. It is a great clinical challenge to effectively treat the cutaneous wound and regenerate the damaged skin. Hydrogels have shown great promise for skin wound healing through the rational design and preparation to endow with specific functionalities. In the mini review, we firstly introduce the design and construction of various types of hydrogels based on their bonding chemistry during cross-linking. Then, we summarize the recent research progress on the functionalization of bioactive hydrogel dressings for skin wound healing, including anti-bacteria, anti-inflammatory, tissue proliferation and remodeling. In addition, we highlight the design strategies of responsive hydrogels to external physical stimuli. Ultimately, we provide perspectives on future directions and challenges of functional hydrogels for skin wound healing.

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Rational Design and Preparation of Functional Hydrogels for Skin Wound Healing

In this work, a stretchable, dual thermo-responsive and strain-responsive ionogel has been synthesized by one-step photopolymerization. The obtained ionogel shows an ultrahigh stretchability (∼3000%), a high ionic conductivity (up to 3.1 mS/cm), and a good temperature tolerance (-40 to 300 °C). Importantly, these ionogels show an upper critical solution temperature-type phase transition with a wide tunable phase-transition temperature (17.5-42.5 °C) and reversible color/transparency switching. In particular, the as-prepared ionogel-based flexible/wearable temperature monitors and smart windows show an excellent designability and programmability, temperature modulation ability, and thermal responsiveness. Moreover, the ionogels-based strain sensors have temperature- and strain-dual responsibility and a broad strain-sensing range (1-700%), which can effectively monitor various motions. This strategy of fabricating dual thermo- and strain-responsive ionogels by using a one-step method and only one polymer holds great promise for the next generation of multifunctional stimuli-responsive materials.

Dual Thermo-Responsive and Strain-Responsive Ionogels for Smart Windows and Temperature/Motion Monitoring.

Iodophor (povidone-iodine) has been widely used for antibacterial applications in the clinic. Yet, limited progress in the field of iodine-based bactericides has been achieved since the invention of iodophor. Herein, a blue polyvinyl alcohol-iodine (PAI) complex-based antibacterial hydrogel is explored as a new generation of biocompatible iodine-based bactericides. The obtained PAI hydrogel maintains laser triggered liquefaction, thermochromic, and photothermal features for highly efficient elimination of bacteria. In vitro antibacterial test reveals that the relative bacteria viabilities of Escherichia coli (E.coli) and methicillin-resistant Staphylococcus aureus (MRSA) incubated with PAI hydrogel are only 8% and 3.8%, respectively. Upon single injection of the PAI hydrogel, MRSA-infected open wounds can be efficiently healed in only 5 days, and the healing speed is further accelerated by laser irradiation due to the dynamic interaction between iodine and polyvinyl alcohol, causing up to ∼29% of wound area being closed on day 1. In addition, a safe threshold temperature of skin scald (∼45 °C) emerges for PAI hydrogels because of thermochromic properties, avoiding thermal injuries during irradiation. In addition, no observed toxicity or skin irritation is observed for the PAI hydrogel. This work expands the category of iodine-based bactericides for safe and controllable management of infected wounds.

Thermochromic Polyvinyl Alcohol-Iodine Hydrogels with Safe Threshold Temperature for Infectious Wound Healing

Background Cervical cancer is one of the most common types of gynecological malignancies worldwide. This study aims to develop an immune signature to predict survival in cervical cancer. Method The gene expression data of 296 patients with cervical cancer from The Cancer Genome Atlas database (TCGA) and immune-related genes from the Immunology Database and Analysis Portal (ImmPort) database were included in this study. The immune signature was developed based on prognostic genes. The validation dataset was downloaded from the Gene Expression Omnibus (GEO) database. Result The immune signature namely immune-based prognostic score (IPRS) was developed with 229 genes. Multivariate analysis revealed that the IPRS was an independent prognostic factor for overall survival (OS) and progression-free survival (PFS) in patients with cervical cancer. Patients were stratified into high IPRS and low IPRS groups, and those in the high IPRS group were associated with better survival, which was validated in the validation set. A nomogram with IPRS and stage was constructed to predict mortality in cervical cancer. Conclusions We developed a robust prognostic signature IPRS that could be used to predict patients' survival outcome.

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Development and Validation of a Prognostic Signature Based on Immune Genes in Cervical Cancer

Indium, a low melting point metal, is well-known for constructing eutectic gallium-indium liquid metal. However, unlike liquid metal nanoparticles, the biomedical applications of metallic indium nanoparticles (In NPs) remain in their infancy. Herein, an ultrasound-assisted liquid-reduction synthesis strategy was developed to prepare PEGylated In NPs, which were then used as a high-performance contrast agent for enhancing multiwavelength photoacoustic imaging and second near-infrared (NIR-II) photothermal therapy of the 4T1 breast tumor. The obtained In NPs depicted remarkable optical absorption from the first near-infrared (NIR-I) to NIR-II region and a high photothermal conversion efficiency of 41.3% at 1064 nm, higher than the majority of conventional NIR-II photothermal agents. Upon injection into the tumor, the photoacoustic intensities of the tumor section post-injection were obviously increased by 2.59-, 2.62-, and 4.27-fold of those of pre-injection by using excitation wavelengths of 750, 808, and 970 nm, respectively, depicting an excellent multiwavelength contrast capability of photoacoustic imaging. In addition, efficient ablation of the 4T1 tumor was achieved through the photothermal performance of PEGylated In NPs under NIR-II laser irradiation. Importantly, as the widely used element in the clinic, In NPs were highly biocompatible in vitro and in vivo. Therefore, this work pioneered the biomedical applications of PEGylated In NPs for cancer diagnosis and treatment.

Yu Chen

Papers

Thermochromic Polyvinyl Alcohol-Iodine Hydrogels with Safe Threshold Temperature for Infectious Wound Healing

Development and Validation of a Prognostic Signature Based on Immune Genes in Cervical Cancer

PEGylated Indium Nanoparticles: A Metallic Contrast Agent for Multiwavelength Photoacoustic Imaging and Second Near-Infrared Photothermal Therapy.