Engineering an Organic Nanoplatform for Augmented Pyroeletroimmunotherapy.

Photothermal immunotherapy has shown great promise in the treatment of tumor metastasis. However, the thermal resistance of tumor cells substantially compromises the treatment effect of photothermal immunotherapy. Herein, a high-performance organic pyroelectric nanoplatform, tBu-TPAD-BF2 nanoparticles (NPs), is rationally engineered for the effective pyroelectroimmunotherapy of tumor metastasis. Biocompatible tBu-TPAD-BF2 NPs with excellent pyroelectric and photothermal conversion properties are constructed by assembling organic, low-bandgap pyroelectric molecules with amphiphilic polymers. After internalization by tumor cells, treatment with tBu-TPAD-BF2 NPs causes an apparent temperature elevation upon near-infrared (NIR) laser irradiation, inducing potent immunogenic cell death (ICD). Additionally, the temperature variations under alternating NIR laser irradiation facilitate reactive oxygen species production for pyroelectric therapy, thus promoting ICD activation and lowering thermal resistance. Importantly, in vivo assessments illustrate that tBu-TPAD-BF2 NPs in combination with NIR laser exposure notably inhibit primary and distant tumor proliferation and prominently retarded lung metastasis. RNA profiling reveals that treatment with tBu-TPAD-BF2 NPs markedly suppresses metastasis under NIR laser illumination by downregulating metastasis-related genes and upregulating immune response-associated pathways. Therefore, this study provides a strategy for designing high-performance pyroelectric nanoplatforms to effectively cure tumor metastasis, thereby overcoming the inherent shortcomings of photothermal immunotherapy.

Engineering Photothermal Catalytic CO2 Nanoreactor for Osteomyelitis Treatment by In Situ CO Generation.

Photocatalytic carbon dioxide (CO2) reduction is an effective method for in vivo carbon monoxide (CO) generation for antibacterial use. However, the available strategies mainly focus on utilizing visible-light-responsive photocatalysts to achieve CO generation. The limited penetration capability of visible light hinders CO generation in deep-seated tissues. Herein, a photothermal CO2 catalyst (abbreviated as NNBCs) to achieve an efficient hyperthermic effect and in situ CO generation is rationally developed, to simultaneously suppress bacterial proliferation and relieve inflammatory responses. The NNBCs are modified with a special polyethylene glycol and further embellished by bicarbonate (BC) decoration via ferric ion-mediated coordination. Upon exposure to 1064 nm laser irradiation, the NNBCs facilitated efficient photothermal conversion and in situ CO generation through photothermal CO2 catalysis. Specifically, the photothermal effect accelerated the decomposition of BC to produce CO2 for photothermal catalytic CO production. Benefiting from the hyperthermic effect and in situ CO production, in vivo assessments using an osteomyelitis model confirmed that NNBCs can simultaneously inhibit bacterial proliferation and attenuate the photothermal effect-associated pro-inflammatory response. This study represents the first attempt to develop high-performance photothermal CO2 nanocatalysts to achieve in situ CO generation for the concurrent inhibition of bacterial growth and attenuation of inflammatory responses.

Value of diffusion kurtosis MR imaging and conventional diffusion weighed imaging for evaluating response to first-line chemotherapy in unresectable pancreatic cancer.

OBJECTIVE: To investigate the diagnostic value of diffusion kurtosis magnetic resonance imaging (DKI) and conventional diffusion-weighted imaging (DWI) for evaluating the response to first-line chemotherapy in unresectable pancreatic cancer. MATERIALS AND METHODS: We retrospectively analyzed 21 patients with clinically and pathologically confirmed unresected pancreatic cancer who received palliative chemotherapy. Three-tesla MRI examinations containing DWI sequences with b values of 0, 100, 700, 1400, and 2100 s/mm2 were performed before and after chemotherapy. Parameters included the apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), and mean diffusional kurtosis (MK). The performances of the DWI and DKI parameters in distinguishing the response to chemotherapy were evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Overall survival (OS) was calculated from the date of first treatment to the date of death or the latest follow-up date. RESULTS: The ADCchange and MDchange were significantly higher in the responding group (PR group) than in the nonresponding group (non-PR group) (ADCchange: 0.21 ± 0.05 vs. 0.11 ± 0.09, P = 0.02; MDchange: 0.37 ± 0.24 vs. 0.10 ± 0.12, P = 0.002). No statistical significance was shown when comparing ADCpre, ADCpost, MKpre, MKpost, MKchange, MDpre, and MDpost between the PR and non-PR groups. The ROC curve analysis indicated that MDchange (AUC = 0.898, cutoff value = 0.7143) performed better than ADCchange (AUC = 0.806, cutoff value = 0.1369) in predicting the response to chemotherapy. CONCLUSION: The ADCchange and MDchange demonstrated strong potential for evaluating the response to chemotherapy in unresectable pancreatic cancer. The MDchange showed higher specificity in the classification of PR and non-PR than the ADCchange. Other parameters, including ADCpre, ADCpost, MKpre, MKpost, MKchange, MDpre, and MDpost, are not suitable for response evaluation. The combined model SUMchange demonstrated superior performance compared to the individual DWI and DKI models. Further experiments are needed to evaluate the potential of DWI and DKI parameters in predicting the prognosis of patients with unresectable pancreatic cancer.

Spring Design of Triboelectric Nanogenerator with MXene-Modified Interface for Fluid Energy Harvesting and Water Level Monitoring.

The introduction of two-dimensional materials with high capacitance that are dielectric into the triboelectric interface is critical for the development of a highly efficient triboelectric nanogenerator (TENG) due to its excellent electrical conductivity and versatile surface chemistry. This paper reports a spring-structured multilayer TENG (S-TENG), where a Nb2CTx MXene-PVDF composite was chosen as the triboelectric electrode for increasing the dielectric and surface charge density. The intense electrostatic interaction of the strong hydrogen bonds between anions on the MXene surface and hydrogen atoms of PVDF chains not only creates a dipole in responding to the applied electric field but also promotes the formation of a piezoelectric phase and induces a strong interface coupling effect. Consequently, an output power enhancement of 300% was shown in comparison with pure PVDF, and a spring-like design with a multilayer structure further increases the space utilization and contact area and presents an output voltage of 420 V, a current density of 1.47 mA/m2, and a maximal output power density of 619 mW/m2. In addition, the as-prepared S-TENG can serve as both a fluid energy harvester on an urban river and a real-time monitor to realize the automatic alarm of water level warning.

Engineering Versatile Nanomedicines for Ultrasonic Tumor Immunotherapy.

Due to the specific advantages of ultrasound (US) in therapeutic disease treatments, the unique therapeutic US technology has emerged. In addition to featuring a low-invasive targeted cancer-cell killing effect, the therapeutic US technology has been demonstrated to modulate the tumor immune landscape, amplify the therapeutic effect of other antitumor therapies, and induce immunosensitization of tumors to immunotherapy, shedding new light on the cancer treatment. Tremendous advances in nanotechnology are also expected to bring unprecedented benefits to enhancing the antitumor efficiency and immunological effects of therapeutic US, as well as therapeutic US-derived bimodal and multimodal synergistic therapies. This comprehensive review summarizes the immunological effects induced by different therapeutic US technologies, including ultrasound-mediated micro-/nanobubble destruction (UTMD/UTND), sonodynamic therapy (SDT), and focused ultrasound (FUS), as well as the main underlying mechanisms involved. It is also discussed that the recent research progress of engineering intelligent nanoplatform in improving the antitumor efficiency of therapeutic US technologies. Finally, focusing on clinical translation, the key issues and challenges currently faced are summarized, and the prospects for promoting the clinical translation of these emerging nanomaterials and ultrasonic immunotherapy in the future are proposed.

Rosmarinic acid nanomedicine for rheumatoid arthritis therapy: Targeted RONS scavenging and macrophage repolarization.

The infiltration of inflammatory cells, especially macrophages, integrated with the production of reactive oxygen and nitrogen species (RONS) and the release of inflammatory cytokines play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Synergistic combination of RONS scavenging and macrophage repolarization from pro-inflammatory M1 phenotype towards anti-inflammatory M2 phenotype, provides a promising strategy for efficient RA treatment. Herein, this study reported a unique self-assembly strategy to construct distinct rosmarinic acid nanoparticles (RNPs) for efficient RA treatment using the naturally occurring polyphenol-based compound, rosmarinic acid (RosA). The designed RNPs exhibited favorable capability in scavenging RONS and pro-inflammatory cytokines produced by macrophages. Attributing to the widened vascular endothelial-cell gap at inflammation sites, RNPs could target and accumulate at the inflammatory joints of collagen-induced arthritis (CIA) rats for guaranteeing therapeutic effect. In vivo investigation demonstrated that RNPs alleviated the symptoms of RA, including joint swelling, synovial hyperplasia, cartilage degradation, and bone erosion in CIA rats. Additionally, the designed RNPs promoted macrophage polarization from M1 phenotype towards M2 phenotype, resulting in the suppressed progression of RA. Therefore, this research represents the representative paradigm for RA therapy using antioxidative nanomedicine deriving from the natural polyphenol-based compound.

Atomic vacancies-engineered ultrathin trimetallic nanozyme with anti-inflammation and antitumor performances for intestinal disease treatment.

Colitis-associated colorectal cancer, which represents a highly aggressive subtypes of colorectal cancer, requires concurrent antitumor and anti-inflammation therapies in clinic. Herein, we successfully engineered Ru38Pd34Ni28 ultrathin trimetallic nanosheets (TMNSs) by introducing diverse transition metal atoms into the structure of RuPd nanosheets. Density functional theory (DFT) calculations reveal that the elaborate introduction of transition metal Ru and Ni facilitates the formation of Ru-O and Ni-O bonds on the surface of TMNSs for efficient reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavenging, respectively. Moreover, the engineered abundant atomic vacancies on their surface conspicuously improve the performance in eliminating reactive oxygen and nitrogen species (RONS). The designed TMNSs act as a multi-metallic nanocatalyst with RONS elimination performance for chronic colitis treatment by relieving inflammation, as well as photothermal conversion capability for colon cancer therapy by inducing hyperthermia effect. Profiting from the excellent RONS scavenging activities, TMNSs can down-regulate the expression levels of the pro-inflammatory factors, thereby leading to prominent therapeutic efficacy against dextran sulfate sodium-induced colitis. Benefiting from the high photothermal performance, TMNSs cause significant suppression of CT-26 tumors without obvious recurrence. This work provides a distinct paradigm to design multi-metallic nanozymes for colon disease treatment by elaborate introduction of transition metal atoms and engineering of atomic vacancies.

Bifunctional MXene-Augmented Retinal Progenitor Cell Transplantation for Retinal Degeneration.

Retinal degeneration, characterized by the progressive loss of retinal neurons, is the leading cause of incurable visual impairment. Retinal progenitor cells (RPCs)-based transplantation can facilitate sight restoration, but the clinical efficacy of this process is compromised by the imprecise neurogenic differentiation of RPCs and undermining function of transplanted cells surrounded by severely oxidative retinal lesions. Here, it is shown that ultrathin niobium carbide (Nb2 C) MXene enables performance enhancement of RPCs for retinal regeneration. Nb2 C MXene with moderate photothermal effect markedly improves retinal neuronal differentiation of RPCs by activating intracellular signaling, in addition to the highly effective RPC protection by scavenging free radicals concurrently, which has been solidly evidenced by the comprehensive biomedical assessments and theoretical calculations. A dramatically increased neuronal differentiation is observed upon subretinal transplantation of MXene-assisted RPCs into the typical retinal degeneration 10 (rd10) mice, thereby contributing to the efficient restoration of retinal architecture and visual function. The dual-intrinsic function of MXene synergistically aids RPC transplantation, which represents an intriguing paradigm in vision-restoration research filed, and will broaden the multifunctionality horizon of nanomedicine.

Ultrasound-Triggered Cascade Amplification of Nanotherapy.

Ultrasound (US)-triggered cascade amplification of nanotherapies has attracted considerable attention as an effective strategy for cancer treatment. With the remarkable advances in materials chemistry and nanotechnology, a large number of well-designed nanosystems have emerged that incorporate presupposed cascade amplification processes and can be activated to trigger therapies such as chemotherapy, immunotherapy, and ferroptosis, under exogenous US stimulation or specific substances generated by US actuation, to maximize antitumor efficacy and minimize detrimental effects. Therefore, summarizing the corresponding nanotherapies and applications based on US-triggered cascade amplification is essential. This review comprehensively summarizes and highlights the recent advances in the design of intelligent modalities, consisting of unique components, distinctive properties, and specific cascade processes. These ingenious strategies confer unparalleled potential to nanotherapies based on ultrasound-triggered cascade amplification and provide superior controllability, thus overcoming the unmet requirements of precision medicine and personalized treatment. Finally, the challenges and prospects of this emerging strategy are discussed and it is expected to encourage more innovative ideas and promote their further development.

Radical-Scavenging and Subchondral Bone-Regenerating Nanomedicine for Osteoarthritis Treatment.

Osteoarthritis (OA) is characterized by cartilage degradation and subchondral bone remodeling. However, most available studies focus on either cartilage degradation or subchondral bone lesion, alone, and rarely pay attention to the synergy of these two pathological changes. Herein, a dual-functional medication is developed to simultaneously protect cartilage and achieve subchondral bone repair. Black phosphorus nanosheets (BPNSs), with a strong reactive oxygen species (ROS)-scavenging capability and high biocompatibility, also present a notable promoting effect in osteogenesis. BPNSs efficiently eliminate the intracellular ROS and, thus, protect the inherent homeostasis between cartilage matrix anabolism and catabolism. RNA sequencing results of BPNSs-treated OA chondrocytes further reveal the restoration of chondrocyte function, activation of antioxidant enzymes, and regulation of inflammation. Additional in vivo assessments solidly confirm that BPNSs inhibit cartilage degradation and prevent OA progression. Meanwhile, histological evaluation and microcomputed tomography (micro-CT) scanning analysis verify the satisfying disease-modifying effects of BPNSs on OA. Additionally, the excellent biocompatibility of BPNSs enables them as a competitive candidate for OA treatment. This distinct disease-modifying treatment of OA on the basis of BPNSs provides an insight and paradigm on the dual-functional treatment strategy focusing on both cartilage degradation and subchondral bone lesion in OA and explores a broader biomedical application of BPNS nanomedicine in orthopedics.

3D-CEUS tracking of injectable chemo-sonodynamic therapy-enabled mop-up of residual renal cell carcinoma after thermal ablation.

Thermal ablation (TA), as a minimally invasive therapeutic technique, has been extensively used to the treatment of solid tumors, such as renal cell carcinoma (RCC), which, unfortunately, still fails to overcome the high risk of local recurrence and distant metastasis since the incomplete ablation cannot be ignored due to various factors such as the indistinguishable tumor margins and limited ablation zone. Herein, we report the injectable thermosensitive hydrogel by confining curcumin (Cur)-loaded hollow mesoporous organosilica nanoparticles (Cur@HMON@gel) which can locate in tumor site more than half a month and mop up the residual RCC under ultrasound (US) irradiation after transforming from colloidal sol status to elastic gel matrix at physiological temperature. Based on the US-triggered accelerated diffusion of the model chemotherapy drug with multi-pharmacologic functions, the sustained and controlled release of Cur has been demonstrated in vitro. Significantly, US is employed as an external energy to trigger Cur, as a sonosensitizer also, to generate reactive oxygen species (ROS) for sonodynamic tumor therapy (SDT) in parallel. Tracking by the three-dimensional contrast-enhanced ultrasound (3D-CEUS) imaging, the typical decreased blood perfusions have been observed since the residual xenograft tumor after incomplete TA were effectively suppressed during the chemo-sonodynamic therapy process. The high in vivo biocompatibility and biodegradability of the multifunctional nanoplatform confined by thermogel provide the potential of their further clinical translation for the solid tumor eradication under the guidance and monitoring of 3D-CEUS.

From Triboelectric Nanogenerator to Multifunctional Triboelectric Sensors: A Chemical Perspective toward the Interface Optimization and Device Integration.

Triboelectric nanogenerators (TENGs) have intrigued scientists for their potential to alleviate the energy shortage crisis and facilitate self-powered sensors. Triboelectric interfaces containing triboelectric functionalized molecular groups and tunable surface charge densities are important for improving the electrical output capability of TENGs and the versatility of future electronics. In this review, following an introduction to the fundamental progress of TENG systems for mechanic energy harvesting, surface modifications that aim to increase the surface charge density and functionality are highlighted, with an emphasis on interfacial chemical modification and triboelectric energetics/dynamics optimization for efficient electrostatic induction and charge transfer. Recent advances in assemblies of multifunctional triboelectric sensing are briefly introduced, and future challenges and chemical perspectives in the field of TENG-based electronics are concisely reviewed. This review presents and advances the understanding of the state-of-the-art chemical strategies toward rational triboelectric interface engineering and system assembly and is expected to guide the rational design of highly efficient and versatile triboelectric sensing.

Self-Assembled Aza-Boron-Dipyrromethene for Ferroptosis-Boosted Sonodynamic Therapy.

The presence of apoptosis inhibition proteins renders the cancer cells resistant to apoptosis, severely compromising the antitumor efficacy of sonodynamic therapy (SDT). Here, an intelligent anticancer nanoplatform based on an Aza-boron-dipyrromethene dye (denoted as Aza-BDY) is elaborately established for ferroptosis augmented SDT through cysteine (Cys) starvation. After endocytosis by tumor cells, Aza-BDY serves as both a ferroptosis inducing agent and a sonosensitizer for tumor treatment. The specific Cys response facilitates the disruption of redox homeostasis and initiation of cellular ferroptosis. Meanwhile, the released sonosensitizer causes efficient SDT and augments ferroptosis under ultrasound irradiation. Detailed in vitro and in vivo investigations demonstrate that the synergistic effect of Cys depletion and singlet oxygen (1 O2 ) generation significantly induces cancer-cell death and suppresses tumor proliferation with a high inhibition rate of 97.5 %.

Sequential Ultrasound-Triggered and Hypoxia-Sensitive Nanoprodrug for Cascade Amplification of Sonochemotherapy.

Hypoxia, the typical and conspicuous characteristic of most solid tumors, worsens the tumor invasiveness and metastasis. Here, we engineered a sequential ultrasound (US)/hypoxia-sensitive sonochemotherapeutic nanoprodrug by initially synthesizing the hypoxia-activated azo bond-containing camptothecin (CPT) prodrug (CPT2-Azo) and then immobilizing it into the mesopores of sonosensitizer-integrated metal organic frameworks (MOF NPs). Upon entering the hypoxic tumor microenvironment (TME), the structure of CPT2-Azo immobilized MOFs (denoted as MCA) was ruptured and the loaded nontoxic CPT2-Azo prodrug was released from the MOF NPs. Under US actuation, this sonochemotherapeutic nanoprodrug not only promoted sonosensitizer-mediated sonodynamic therapy (SDT) via the conversion of oxygen into cytotoxic reactive oxygen species (ROS) but also aggravated hypoxia in the TME by elevating oxygen consumption. The exacerbated hypoxia in turn served as a positive amplifier to boost the activation of CPT2-Azo, and the controllable release of toxic chemotherapeutic drug (CPT), and compensated the insufficient treatment efficacy of SDT. In vitro and in vivo evaluations confirmed that sequential SDT and tumor hypoxia-activated sonochemotherapy promoted the utmost of tumor hypoxia and thereby contributed to the augmented antitumor efficacy, resulting in conspicuous apoptotic cell death and noteworthy tumor suppression in vivo. Our work provides a distinctive insight into the exploitation of the hypoxia-activated sonochemotherapeutic nanoprodrug that utilizes the hypoxic condition in TME, a side effect of SDT, to initiate chemotherapy, thus causing a significantly augmented treatment outcome compared to conventional SDT.

Engineering 2D Cu-composed metal-organic framework nanosheets for augmented nanocatalytic tumor therapy.

The engineered nanoformulation that can be activated by intracellular tumor microenvironment, including acidic pH, overexpressed H2O2, and high concentration of glutathione (GSH), features high efficacy to eradicate tumor cells with the intrinsic specificity and therapeutic biosafety. However, the relatively slow reaction rate of traditional Fe2+-mediated Fenton reaction induces the low production amount of reactive oxygen species (ROS) and subsequently the limited therapeutic outcome against tumors. Here, we established Cu (II)-based two-dimensional (2D) metal-organic framework (MOF) nanosheets as a distinct chemoreactive nanocatalyst for GSH-triggered and H2O2-augmented chemodynamic therapy (CDT), depending on the "AND" logic gate, for significant tumor suppression. After internalization by tumor cells, the MOF catalytic nanosheets reacted with local GSH for inducing GSH consumption and reducing the Cu2+ into Cu+. Subsequently, abundant hydroxyl radicals (·OH) generation was achieved via Cu+-mediated Fenton-like catalytic reaction. The dual effects of ·OH production and GSH depletion thus enhanced ROS production and accumulation in tumor cells, leading to significant cellular apoptosis and tumor inhibition, which was systematically demonstrated in both 4T1 and MDA-MB-231 tumor models. Therefore, GSH and H2O2, serve as an "AND" logic gate to trigger the Cu+-mediated Fenton-like reaction and reduce GSH level for augmented CDT with high therapeutic specificity and efficacy, thus inducing cellular apoptosis primarily through ferroptosis at the RNA sequence level.

Engineering Electronic Band Structure of Binary Thermoelectric Nanocatalysts for Augmented Pyrocatalytic Tumor Nanotherapy.

Photothermal therapy (PTT) has emerged as a distinct therapeutic modality owing to its noninvasiveness and spatiotemporal selectivity. However, heat-shock proteins (HSPs) endow tumor cells with resistance to heat-induced apoptosis, severely lowering the therapeutic efficacy of PTT. Here, a high-performance pyroelectric nanocatalyst, Bi13 S18 I2 nanorods (NRs), with prominent pyroelectric conversion and photothermal conversion performance for augmented pyrocatalytic tumor nanotherapy, is developed. Canonical binary compounds are reconstructed by inserting a third biocompatible agent, thus facilitating the formation of Bi13 S18 I2 NRs with enhanced pyrocatalytic conversion efficiency. Under 808 nm laser irradiation, Bi13 S18 I2 NRs induce a conspicuous temperature elevation for photonic hyperthermia. In particular, Bi13 S18 I2 NRs harvest pyrocatalytic energy from the heating and cooling alterations to produce abundant reactive oxygen species, which results in the depletion of HSPs and hence the reduction of thermoresistance of tumor cells, thereby significantly augmenting the therapeutic efficacy of photothermal tumor hyperthermia. By synergizing the pyroelectric dynamic therapy with PTT, tumor suppression with a significant tumor inhibition rate of 97.2% is achieved after intravenous administration of Bi13 S18 I2 NRs and subsequent exposure to an 808 nm laser. This work opens an avenue for the design of high-performance pyroelectric nanocatalysts by reconstructing canonical binary compounds for therapeutic applications in biocatalytic nanomedicine.

Engineering Oxygen-Irrelevant Radical Nanogenerator for Hypoxia-Independent Magnetothermodynamic Tumor Nanotherapy.

Tumor hypoxia substantially lowers the treatment efficacy of oxygen-relevant therapeutic modalities because the production of reactive oxygen species in oxygen-relevant anticancer modalities is highly dependent on oxygen level in tumor tissues. Here a distinctive magnetothermodynamic anticancer strategy is developed that takes the advantage of oxygen-irrelevant free radicals produced from magnetothermal decomposable initiators for inducing cancer-cell apoptosis in vitro and tumor suppression in vivo. Free-radical nanogenerator is constructed through in situ engineering of a mesoporous silica coating on the surface of superparamagnetic Mn and Co-doped nanoparticles (MnFe2 O4 @CoFe2 O4 , denoted as Mag) toward multifunctionality, where mesoporous structure provides reservoirs for efficient loading of initiators and the Mag core serves as in situ heat source under alternating magnetic field (AMF) actuation. Upon exposure to an exogenous AMF, the magnetic hyperthermia effect of superparamagnetic core lead to the rapid decomposition of the loaded/delivered initiators (AIPH) to produce oxygen-irrelevant free radicals. Both the magnetothermal effect and generation of toxic free radicals under AMF actuation are synergistically effective in promoting cancer-cell death and tumor suppression in the hypoxic tumor microenvironment. The prominent therapeutic efficacy of this radical nanogenerator represents an intriguing paradigm of oxygen-irrelevant nanoplatform for AMF-initiated synergistic cancer treatment.

Piezoelectric Nanogenerator for Highly Sensitive and Synchronous Multi-Stimuli Sensing.

Smart sensors are expected to be sustainable, stretchable, biocomfortable, and tactile over time, either in terms of mechanical performance, reconfigurability, or energy supply. Here, a biocompatible piezoelectric electronic skin (PENG) is demonstrated on the base of PZT-SEBS (lead zirconate titanate and styrene ethylene butylene styrene) composite elastomer. The highly elastic (with an elasticity of about 950%) PENG can not only harvest mechanical energy from ambient environment, but also show low toxicity and excellent sensing performance toward multiple external stimuli. The synchronous and independent sensing performance toward motion capture, temperature, voice identification, and especially the dual-dimensional force perception promotes its wide application in physiological, sound restoration, and other intelligent systems.

Sono-Controllable and ROS-Sensitive CRISPR-Cas9 Genome Editing for Augmented/Synergistic Ultrasound Tumor Nanotherapy.

The potential of the cluster regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9)-based therapeutic genome editing is severely hampered by the difficulties in precise regulation of the in vivo activity of the CRISPR-Cas9 system. Herein, sono-controllable and reactive oxygen species (ROS)-sensitive sonosensitizer-integrated metal-organic frameworks (MOFs), denoted as P/M@CasMTH1, are developed for augmented sonodynamic therapy (SDT) efficacy using the genome-editing technology. P/M@CasMTH1 nanoparticles comprise singlet oxygen (1 O2 )-generating MOF structures anchored with CRISPR-Cas9 systems via 1 O2 -cleavable linkers, which serve not only as a delivery vector of CRISPR-Cas9 targeting MTH1, but also as a sonoregulator to spatiotemporally activate the genome editing. P/M@CasMTH1 escapes from the lysosomes, harvests the ultrasound (US) energy and converts it into abundant 1 O2 to induce SDT. The generated ROS subsequently trigger cleavage of ROS-responsive thioether bonds, thus inducing controllable release of the CRISPR-Cas9 system and initiation of genome editing. The genomic disruption of MTH1 conspicuously augments the therapeutic efficacy of SDT by destroying the self-defense system in tumor cells, thereby causing cellular apoptosis and tumor suppression. This therapeutic strategy for synergistic MTH1 disruption and abundant 1 O2 generation provides a paradigm for augmenting SDT efficacy based on the emerging nanomedicine-enabled genome-editing technology.

Chemotherapy-enabled/augmented cascade catalytic tumor-oxidative nanotherapy.

Catalytic cascade transformations, which occur in spatially constrained tumor environment to generate therapeutic moieties from prodrugs or intrinsic species, are highly desirable for precise cancer therapy. Nevertheless, it is high challenging to engineer a cascade nanoreactor with tumor microenvironment (TME)-responsive capability for synergistic tumor therapy. Inspired by the biocatalytic cascades in biological processes, here, a tumor-specific nanoreactor was established to activate cascade reactions for oxidative stress-augmented chemotherapy by the integration of an artificial enzyme, Pt(IV)-based prodrug (Pt(IV)), with Cu(II)-based metal-organic frameworks (CuMOF). Upon internalization of CuMOF@Pt(IV) by tumor cells, in addition to chemotherapeutic effect, the activated cisplatin by glutathione (GSH) reduction is capable of acting as an artificial enzyme to elevate the hydrogen peroxide (H2O2) level through cascade reactions for augmenting the therapeutic efficacy of Cu+-mediated chemodynamic therapy (CDT). Meanwhile, CuMOF@Pt(IV) specifically deplete overexpressed GSH at tumor sites, thus amplifying tumor oxidative stress, and finally leading to augmented antitumor efficacy. The orchestrated cooperative effect of chemotherapy and oxidative stress presents splendid therapeutic efficacy on tumor-bearing mice with negligible adverse effects. Therefore, this cascade nanoreactor provides exciting opportunities to develop complementary therapeutic modalities for precise cancer treatment.