Confined Assembly of Hydrated Vanadium Oxide into Hollow Mesoporous Carbon Nanospheres for Fast and Stable K+ Storage Capability.

The rational structural design of the electrode materials is significant to enhance the electrochemical performance for potassium ion storage, benefiting from the shortened ion diffusion distance, increased conductivity, and pseudo-capacitance promotion. Herein, hydrated vanadium oxide (HVO) nanosheets with enriched oxygen defects are well confined into hollow mesoporous carbon spheres (HMCS), producing Od -VOH@C nanospheres through one-step hydrothermal reaction. Attributed to the restricted growth in the HMCS, the HVO nanosheets are loosely packed, generating abundant interfacial boundaries and large specific areas. As a result, Od -VOH@C nanospheres show increased reaction kinetics and well buffer the volume effects for the K+ storage. Od -VOH@C delivers stable capacities of 138 mAh g-1 at 2.0 A g-1 over 10 000 cycles in half-cells attributed to the high pseudo-capacitance contribution. The K+ storage mechanism of insertion and conversion reaction is confirmed by ex situ X-ray diffraction, Raman, and X-ray photoelectron spectroscopy analyses. Moreover, the symmetric potassium-ion capacitors of Od -VOH@C//Od -VOH@C deliver a high energy density of 139.6 Wh kg-1 at the power density of 948.3 W kg-1 .

The effects of ginsenosides on platelet aggregation and vascular intima in the treatment of cardiovascular diseases: From molecular mechanisms to clinical applications.

Thrombosis initiated by abnormal platelet aggregation is a pivotal pathological event that precedes most cases of cardiovascular diseases (CVD). Recently, growing evidence indicates that platelet could be a potential target for CVD prevention. However, as the conventional antithrombotic management strategy, applications of current antiplatelet agents are somewhat limited by their various side effects, such as bleeding risk and drug resistance. Hence, efforts have been made to search for agents as complementary therapies. Ginsenoside, the principal active component extracted from Panax ginseng, has gained much attention for its regulations on multiple crucial events of platelet aggregation. From structural characteristics to clinical applications, this review anatomized the intrinsic structure-function relationship of antiplatelet potency of ginsenosides, and the involved signal pathways were specifically summarized. Additionally, the emphasis was placed on clinical studies that investigate the antithrombotic efficacy of ginsenosides in the treatment of CVD. Further, a broad overview of approaches for improving the bioavailability of ginsenosides was concluded. Limitations and prospects of current studies were also discussed. This study may provide some new insights into the systematic understanding of ginsenosides in CVD treatment and lay a foundation for future research.

Accurate Wide Angle SAR Imaging Based on LS-CS-Residual.

Wide angle synthetic aperture radar (WASAR) receives data from a large angle, which causes the problem of aspect dependent scattering. L 1 regularization is a common compressed sensing (CS) model. The L 1 regularization based WASAR imaging method divides the whole aperture into subapertures and reconstructs the subaperture images individually. However, the aspect dependent scattering recovery of it is not accurate. The subaperture images of WASAR can be regarded as the SAR video. The support set among the different frames of SAR video are highly overlapped. Least squares on compressed sensing residuals (LS-CS-Residuals) can reconstruct the time sequences of sparse signals which change slowly with time. This is to replace CS on the observation by CS on the least squares (LS) residual computed using the prior estimate of the support. In this paper, we introduce LS-CS-Residual into WASAR imaging. In the iteration of LS-CS-Residual, the azimuth-range decoupled operators are used to avoid the huge memory cost. Real data processing results show that LS-CS-Residual can estimate the aspect dependent scatterings of the targets more accurately than CS based methods.

Efficient Parameter Estimation for Sparse SAR Imaging Based on Complex Image and Azimuth-Range Decouple.

Sparse signal processing theory has been applied to synthetic aperture radar (SAR) imaging. In compressive sensing (CS), the sparsity is usually considered as a known parameter. However, it is unknown practically. For many functions of CS, we need to know this parameter. Therefore, the estimation of sparsity is crucial for sparse SAR imaging. The sparsity is determined by the size of regularization parameter. Several methods have been presented for automatically estimating the regularization parameter, and have been applied to sparse SAR imaging. However, these methods are deduced based on an observation matrix, which will entail huge computational and memory costs. In this paper, to enhance the computational efficiency, an efficient adaptive parameter estimation method for sparse SAR imaging is proposed. The complex image-based sparse SAR imaging method only considers the threshold operation of the complex image, which can reduce the computational costs significantly. By utilizing this feature, the parameter is pre-estimated based on a complex image. In order to estimate the sparsity accurately, adaptive parameter estimation is then processed in the raw data domain, combining with the pre-estimated parameter and azimuth-range decouple operators. The proposed method can reduce the computational complexity from a quadratic square order to a linear logarithm order, which can be used in the large-scale scene. Simulated and Gaofen-3 SAR data processing results demonstrate the validity of the proposed method.

Comparison of Raw Data-Based and Complex Image-Based Sparse SAR Imaging Methods.

Sparse signal processing has already been introduced to synthetic aperture radar (SAR), which shows potential in improving imaging performance based on raw data or a complex image. In this paper, the relationship between a raw data-based sparse SAR imaging method (RD-SIM) and a complex image-based sparse SAR imaging method (CI-SIM) is compared and analyzed in detail, which is important to select appropriate algorithms in different cases. It is found that they are equivalent when the raw data is fully sampled. Both of them can effectively suppress noise and sidelobes, and hence improve the image performance compared with a matched filtering (MF) method. In addition, the target-to-background ratio (TBR) or azimuth ambiguity-to-signal ratio (AASR) performance indicators of RD-SIM are superior to those of CI-SIM in down-sampling data-based imaging, nonuniform displace phase center sampling, and sparse SAR imaging model-based azimuth ambiguity suppression.

Carrier-Free, Pure Nanodrug Formed by the Self-Assembly of an Anticancer Drug for Cancer Immune Therapy.

Ursolic acid (UA) is a food-plant-derived natural product which has good anticancer activities and low toxicity. However, the poor water solubility of UA limits its application in clinic. To address this issue, we developed a carrier-free nanodrug by self-assembly of UA. Here, we showed that UA nanoparticles (NPs) have a near-spherical shape with a diameter of ∼150 nm. UA NPs exhibited higher antiproliferative activity; significantly caused apoptosis; decreased the expression of COX-2/VEGFR2/VEGFA; and increased the immunostimulatory activity of TNF-α, IL-6, and IFN-ß and decreased the activity of STAT-3 in A549 cells in vitro. Furthermore, UA NPs could inhibit tumor growth and have the ability of liver protection in vivo. More importantly, UA NPs could significantly improve the activation of CD4+ T-cells, which indicated that UA NPs have the potential for immunotherapy. Overall, a carrier-free UA nanodrug may be a promising drug to further enhance their anticancer efficacy and immune function.

Analysis of differential effects of host plants on the gut microbes of Rhoptroceros cyatheae.

As an indispensable part of insects, intestinal symbiotic bacteria play a vital role in the growth and development of insects and their adaptability. Rhoptroceros cyatheae, the main pest of the relict plant Alsophila spinulosa, poses a serious threat to the development of the A. spinulosa population. In the present study, 16S rDNA and internal transcribed spacer high-throughput sequencing techniques were used to analyze the structure of intestinal microbes and the diversity of the insect feeding on two different plants, as well as the similarities between the intestinal microorganisms of R. cyatheae. The dominant bacteria of leaf endophytes were also compared based on the sequencing data. The results showed that Proteobacteria, Firmicutes, and Actinobacteria were the dominant phyla of intestinal bacteria, and Ascomycota was the dominant phylum of intestinal fungi. Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Methylobacterium-Methylorubrum, and Enterococcus were the dominant genera in the intestine of R. cyatheae feeding on two plants, and the relative abundance was significantly different between the two groups. Candida was the common dominant genus of intestinal fungi in the two groups, and no significant difference was observed in its abundance between the two groups. This showed that compared with the intestinal fungi of R. cyatheae, the abundance of the intestinal bacteria was greatly affected by food. The common core microbiota between the microorganisms in A. spinulosa leaves and the insect gut indicated the presence of a microbial exchange between the two. The network correlation diagram showed that the gut microbes of R. cyatheae feeding on Gymnosphaera metteniana were more closely related to each other, which could help the host to better cope with the adverse external environment. This study provides a theoretical basis for the adaptation mechanism of R. cyatheae and a new direction for the effective prevention and control of R. cyatheae.

Manganese-induced Photothermal-Ferroptosis for synergistic tumor therapy.

Ferroptosis-related tumor therapy based on nanomedicines has recently gained significant attention. However, the therapeutic performance is still hindered by the tumor's physical barriers such as the fibrotic tumor matrix and elevated interstitial fluid pressure, as well as chemical barriers like glutathione (GSH) overabundance. These physicochemical barriers impede the bioavailability of nanomedicines and compromise the therapeutic efficacy of lipid reactive oxygen species (ROS). Thus, this study pioneers a manganese-mediated overcoming of physicochemical barriers in the tumor microenvironment using organosilica-based nanomedicine (MMONs), which bolsters the synergy of photothermal-ferroptosis treatment. The MMONs display commendable proficiency in overcoming tumor physical barriers, due to their MnO2-mediated shape-morphing and softness-transformation ability, which facilitates augmented cellular internalization, enhanced tumor accumulation, and superior drug penetration. Also, the MMONs possess excellent capability in chemical barrier overcoming, including MnO2-mediated dual GSH clearance and enhanced ROS generation, which facilitates ferroptosis and heat shock protein inhibition. Notably, the resulting integration of physical and chemical barrier overcoming leads to amplified photothermal-ferroptosis synergistic tumor therapy both in vitro and in vivo. Accordingly, the comparative proteomic analysis has identified promoted ferroptosis with a transient inhibitory response observed in the mitochondria. This research aims to improve treatment strategies to better fight the complex defenses of tumors.

Mitochondria-targeted polyprodrug nanoparticles induce mitochondrial stress for immunogenic chemo-photodynamic therapy of ovarian cancer.

Hypoimmunogenicity and the immunosuppressive microenvironment of ovarian cancer severely restrict the capability of immune-mediated tumor killing. Immunogenic cell death (ICD) introduces a theoretical principle for antitumor immunity by increasing antigen exposure and presentation. Despite recent research progress, the currently available ICD inducers are still very limited, and many of them can hardly induce sufficient ICD based on traditional endoplasmic reticulum (ER) stress. Accumulating evidence indicates that inducing mitochondrial stress usually shows a higher efficiency in evoking large-scale ICD than that via ER stress. Inspired by this, herein, a mitochondria-targeted polyprodrug nanoparticle (named Mito-CMPN) serves as a much superior ICD inducer, effectively inducing chemo-photodynamic therapy-caused mitochondrial stress in tumor cells. The rationally designed stimuli-responsive polyprodrugs, which can self-assemble into nanoparticles, were functionalized with rhodamine B for mitochondrial targeting, cisplatin and mitoxantrone (MTO) for synergistic chemo-immunotherapy, and MTO also serves as a photosensitizer for photodynamic immunotherapy. The effectiveness and robustness of Mito-CMPNs in reversing the immunosuppressive microenvironment is verified in both an ovarian cancer subcutaneous model and a high-grade serous ovarian cancer model. Our results support that the induction of abundant ICD by focused mitochondrial stress is a highly effective strategy to improve the therapeutic efficacy of immunosuppressive ovarian cancer.

Transcriptomics and metabolomics analyses provide insights into resistance genes of tree ferns.

As ancient organisms, tree ferns play a crucial role as an evolutionary bridge between lower and higher plant species, providing various utilitarian benefits. However, they face challenges such as overexploitation, climate change, adverse environmental conditions, and insect pests, resulting in conservation concerns. In this study, we provide an overview of metabolic and transcriptomic resources of leaves in two typical tree ferns, A. spinulosa and A. metteniana, and explore the resistance genes for the first time. The landscape of metabolome showed that the compound skimmin may hold medicinal significance. A total of 111 differentially accumulated metabolites (DAMs) were detected, with pathway enrichment analysis highlighting 14 significantly enriched pathways, including 2-oxocarboxylic acid metabolism possibly associated with environmental adaptations. A total of 14,639 differentially expressed genes (DEGs) were found, among which 606 were resistance (R) genes. We identified BAM1 as a significantly differentially expressed R gene, which is one of the core genes within the R gene interaction network. Both the maximum-likelihood phylogenetic tree and the PPI network revealed a close relationship between BAM1, FLS2, and TMK. Moreover, BAM1 showed a significant positive correlation with neochlorogenic acid and kaempferol-7-O-glucoside. These metabolites, known for their antioxidant and anti-inflammatory properties, likely play a crucial role in the defense response of tree ferns. This research provides valuable insights into the metabolic and transcriptomic differences between A. spinulosa and A. metteniana, enhancing our understanding of resistance genes in tree ferns.

Research progress and application of the CRISPR/Cas9 gene-editing technology based on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is now a common cause of cancer death, with no obvious change in patient survival over the past few years. Although the traditional therapeutic modalities for HCC patients mainly involved in surgery, chemotherapy, and radiotherapy, which have achieved admirable achievements, challenges are still existed, such as drug resistance and toxicity. The emerging gene therapy of clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9-based (CRISPR/Cas9), as an alternative to traditional treatment methods, has attracted considerable attention for eradicating resistant malignant tumors and regulating multiple crucial events of target gene-editing. Recently, advances in CRISPR/Cas9-based anti-drugs are presented at the intersection of science, such as chemistry, materials science, tumor biology, and genetics. In this review, the principle as well as statues of CRISPR/Cas9 technique were introduced first to show its feasibility. Additionally, the emphasis was placed on the applications of CRISPR/Cas9 technology in therapeutic HCC. Further, a broad overview of non-viral delivery systems for the CRISPR/Cas9-based anti-drugs in HCC treatment was summarized to delineate their design, action mechanisms, and anticancer applications. Finally, the limitations and prospects of current studies were also discussed, and we hope to provide comprehensively theoretical basis for the designing of anti-drugs.

Rational design of a minimum nanoplatform for maximizing therapeutic potency: Three birds with one stone.

Therapeutic modalities and drug formulations play a crucial and prominent role in actualizing effective treatment and radical cures of tumors. However, the therapeutic efficiency was severely limited by tumor recurrence and complex multi-step preparation of formulation. Therefore, the exploration of novel nanoparticles via a simple and green synthesis process for conquering traditional obstacles and improving therapeutic efficiency is an appealing, yet remarkably challenging task. Herein, a universal nanoplatform allows all cancerous cell-targeting, acid-responsive, cell imaging, synergistic chemotherapy, and nucleolar targeted phototherapy function was tactfully designed and constructed by using chemotherapeutic agents ursolic acid (UA), sorafenib (SF), and carbon dots (CDs) photosensitizers (PSs). The designed US NPs were formed by self-assembly of UA and SF associated with electrostatic, π-π stacking, and hydrophobic interactions. After hydrogen bonding reaction with CDs, the obtained (denoted as USC NPs) have a relatively uniform size of an average 125.6 nm, which facilitated the favorable accumulation of drugs at the tumor region through a potential enhanced permeability and retention (EPR) effect as compared to their counterpart of free CDs solution. Both in vitro and in vivo studies revealed that the advanced platform commenced synergistic anticancer therapeutic potency, imperceptible systematical toxicity, and remarkable reticence towards drug-resistant cancer cells. Moreover, the CDs PSs possess intrinsic nucleolus-targeting ability. Taken together, this theranostics system can fully play the role of "killing three birds with one stone" in a safe manner, implying a promising direction for exploring treatment strategies for cancer and endowing them with great potential for future translational research and providing a new vision for the advancing of an exceptionally forceful protocol for practical cancer therapy.

Three-pronged attacks by hybrid nanoassemblies involving a natural product, carbon dots, and Cu2+ for synergistic HCC therapy.

Tumor microenvironment (TME) stimuli-responsive nanoassemblies are emerging as promising drug delivery systems (DDSs), which acquire controlled release by structural transformation under exogenous stimulation. However, the design of smart stimuli-responsive nanoplatforms integrated with nanomaterials to achieve complete tumor ablation remains challenging. Therefore, it is of utmost importance to develop TME-based stimuli-responsive DDSs to enhance drug-targeted delivery and release at tumor sites. Herein, we proposed an appealing strategy to construct fluorescence-mediated TME stimulus-responsive nanoplatforms for synergistic cancer therapy by assembling photosensitizers (PSs) carbon dots (CDs), chemotherapeutic agent ursolic acid (UA), and copper ions (Cu2+). First, UA nanoparticles (UA NPs) were prepared by self-assembly of UA, then UA NPs were assembled with CDs via hydrogen bonding force to obtain UC NPs. After combining with Cu2+, the resulting particles (named UCCu2+ NPs) exhibited quenched fluorescence and photosensitization due to the aggregation of UC NPs. Upon entering the tumor tissue, the photodynamic therapy (PDT) and the fluorescence function of UCCu2+ were recovered in response to TME stimulation. The introduction of Cu2+ triggered the charge reversal of UCCu2+ NPs, thereby promoting lysosomal escape. Furthermore, Cu2+ resulted in additional chemodynamic therapy (CDT) capacity by reacting with hydrogen peroxide (H2O2) as well as by consuming glutathione (GSH) in cancer cells through a redox reaction, hence magnifying intracellular oxidative stress and enhancing the therapeutic efficacy due to reactive oxygen species (ROS) therapy. In summary, UCCu2+ NPs provided an unprecedented novel approach for improving the therapeutic efficacy through the three-pronged (chemotherapy, phototherapy, and heat-reinforced CDT) attacks to achieve synergistic therapy.

A drug-delivery depot for epigenetic modulation and enhanced cancer immunotherapy.

DNA methyltransferase inhibitors (DNMTis) have found widespread application in the management of cancer. Zebularine (Zeb), functioning as a demethylating agent, has exhibited notable advantages and enhanced therapeutic efficacy in the realm of tumour immunotherapy. Nevertheless, due to its lack of targeted functionality, standalone Zeb therapy necessitates the administration of a substantially higher dosage. In this investigation, we have devised an innovative nanodrug formulation, comprising the DNA methyltransferase inhibitor Zeb and pH-responsive chitosan (CS), hereinafter referred to as CS-Zeb nanoparticles (NPs). Our findings have unveiled that CS-Zeb NPs manifest heightened drug release within an acidic milieu (pH 5.5) in comparison to a neutral environment (pH 7.4). Furthermore, in vivo studies have conclusively affirmed that, in contrast to equivalent quantities of Zeb in isolation, the nanocomplex significantly curtailed tumour burden and protracted the survival duration of the B16F10 tumour-bearing murine model. Additionally, CS-Zeb NPs elicited an augmentation of CD8+ T cells within the peripheral circulation of mice and tumour-infiltrating lymphocytes (TILs). Notably, the dosage of CS-Zeb NPs was reduced by a remarkable 70-fold when juxtaposed with Zeb administered in isolation. To summarise, our study underscores the potential of CS-Zeb NPs as an alternative chemotherapeutic agent for cancer treatment.

CRISPR/Cas9-based application for cancer therapy: Challenges and solutions for non-viral delivery.

CRISPR/Cas9 genome editing is a promising therapeutic technique, which makes precise and rapid gene editing technology possible on account of its high sensitivity and efficiency. CRISPR/Cas9 system has been proved to able to effectively disrupt and modify genes, which shows great potential for cancer treatment. Current researches proves that virus vectors are capable of effectively delivering the CRISPR/Cas9 system, but immunogenicity and carcinogenicity caused by virus transmission still trigger serious consequences. Therefore, the greatest challenge of CRISPR/Cas9 for cancer therapy lies on how to deliver it to the target tumor site safely and effectively. Non-viral delivery systems with specific targeting, high loading capacity, and low immune toxicity are more suitable than viral vectors, which limited by uncontrollable side effects. Their medical advances and applications have been widely concerned. Herein, we present the molecule mechanism and different construction strategies of CRISPR/Cas9 system for editing genes at the beginning of this research. Subsequently, several common CRISPR/Cas9 non-viral deliveries for cancer treatment are introduced. Lastly, based on the main factors limiting the delivery efficiency of non-viral vectors proposed in the existing researches and literature, we summarize and discuss the main methods to solve these limitations in the existing tumor treatment system, aiming to introduce further optimization and innovation of the CRISPR/Cas9 non-viral delivery system suitable for cancer treatment.

ROS-Triggered Self-Assembled Nanoparticles Based on a Chemo-Sonodynamic Combinational Therapy Strategy for the Noninvasive Elimination of Hypoxic Tumors.

The hypopermeability and hypoxia in the tumor milieu are important factors that limit multiple treatments. Herein, the reactive oxygen species (ROS)-triggered self-assembled nanoparticles (RP-NPs) was constructed. The natural small molecule Rhein (Rh) was encapsulated into RP-NPs as a sonosensitizer highly accumulated at the tumor site. Then highly tissue-permeable ultrasound (US) irradiation induced apoptosis of tumor cells through the excitation of Rh and acoustic cavitation, which prompted the rapid production of large amounts of ROS in the hypoxic tumor microenvironment. In addition, the thioketal bond structures in the innovatively designed prodrug LA-GEM were triggered and broken by ROS to achieve rapid targeted release of the gemcitabine (GEM). Sonodynamic therapy (SDT) increased the tissue permeability of solid tumors and actively disrupted redox homeostasis via mitochondrial pathways to kill hypoxic tumor cells, and the triggered response mechanism to GEM synergistically amplified the effect of chemotherapy. The chemo-sonodynamic combinational treatment approach is highly effective and noninvasive, with promising applications for hypoxic tumor elimination, such as in cervical cancer (CCa) patients who want to maintain their reproductive function.

Engineered Magnetic Polymer Nanoparticles Can Ameliorate Breast Cancer Treatment Inducing Pyroptosis-Starvation along with Chemotherapy.

Nanotechnology has shown a revolution in cancer treatments, including breast cancers. However, there remain some challenges and translational hurdles. Surgery, radiotherapy, and chemotherapy are the primary treatment methods for breast cancer, although drug combinations showed promising results in preclinical studies. Herein we report the development of a smart drug delivery system (DDS) to efficiently treat breast cancer by pyroptosis-starvation-chemotherapeutic combination. Cancer-starvation agent glucose oxidase was chemically attached to synthesized iron oxide nanoparticles which were entrapped inside poly(lactic-co-glycolic acid) along with apoptosis-associated speck-like protein containing a caspase recruitment domain plasmid and paclitaxel (PTX). An emulsion solvent evaporation method was used to prepare the DDS. The surface of the DDS was modified with chitosan to which aptamer was attached to achieve site-specific targeting. Hence, the prepared DDS could be targeted to a tumor site by both external magnet and aptamer to obtain an enhanced accumulation of drugs at the tumor site. The final size of the aptamer-decorated DDS was less than 200 nm, and the encapsulation efficiency of PTX was 76.5 ± 2.5%. Drug release from the developed DDS was much higher at pH 5.5 than at pH 7.4, ensuring the pH sensitivity of the DDS. Due to efficient dual targeting of the DDS, in vitro viability of 4T1 cells was reduced to 12.1 ± 1.6%, whereas the nontargeted group and free PTX group could reduce the viability of cells to 29.2 ± 2.4 and 46.2 ± 1.6%, respectively. Our DDS showed a synergistic effect in vitro and no severe side effects in vivo. This DDS has strong potential to treat various cancers.

Biomimetic polyphenol-coated nanoparticles by Co-assembly of mTOR inhibitor and photosensitizer for synergistic chemo-photothermal therapy.

Rapamycin (RAPA) functions as effectively clinical immunosuppressive agent, its significant tumor growth suppression effect via various pathways in diverse cancers, especially combined with photothermal therapy, is gaining a burgeoning attention. However, its critical defects, low solubility and poor stability, have severely hampered its further application. Herein, RAPA, indocyanine green (ICG) and epigallocatechin gallate (EGCG) serving as chemotherapeutic drug, photosensitizer and biomimetic coatings, respectively, were co-assembled into carrier-free, high biocompatible ICG-RAPA-EGCG nanoparticles (IRE NPs) for synergistic cancer therapy. Particularly, the bioinspired EGCG coatings not only improved the stability of IRE NPs under physiological conditions to avert NPs disassembly and drug release, but also maintained the photostability of ICG to achieve excellent photothermal response. The results indicated that the as-prepared IRE NPs displayed good monodispersity and enhanced stability at various stored media after introducing of EGCG. Compared with monotherapy of RAPA or ICG, IRE NPs showed higher dose-dependent toxicity in MCF-7 cells, HepG2 cells and HeLa cells, especially plus near-infrared laser irradiation. Furthermore, IRE NPs exhibited quicker uptake in cells, higher accumulation in tumor region (even in 48 h) than free ICG and effectively inhibited tumor growth without side effect in H22 tumor-bearing mice. Collectively, the carrier-free IRE NPs provided a simply alternative approach to fabricate RAPA/photosensitizer co-loaded nanoparticles for combinatorial tumor therapy.

A multifunctional theranostics nanosystem featuring self-assembly of alcohol-abuse drug and photosensitizers for synergistic cancer therapy.

Conventional treatments for cancer, such as chemotherapy, surgical resection, and radiotherapy, have shown limited therapeutic efficacy, with severe side effects, lack of targeting and drug resistance for monotherapies, which limit their clinical application. Therefore, combinatorial strategies have been widely investigated in the battle against cancer. Herein, we fabricated a dual-targeted nanoscale drug delivery system based on EpCAM aptamer- and lactic acid-modified low-polyamidoamine dendrimers to co-deliver the FDA-approved agent disulfiram and photosensitizer indocyanine green, combining the imaging and therapeutic functions in a single platform. The multifunctional nanoparticles with uniform size had high drug-loading payload, sustained release, as well as excellent photothermal conversion. The integrated nanoplatform showed a superior synergistic effect in vitro and possessed precise spatial delivery to HepG2 cells with the dual-targeting nanocarrier. Intriguingly, a robust anticancer response of chemo-phototherapy was achieved; chemotherapy combined with the efficacy of phototherapy to cause cellular apoptosis of HepG2 cells (>35%) and inhibit the regrowth of damaged cells. Furthermore, the theranostic nanosystem displayed fluorescence imaging in vivo, attributed to its splendid accumulation in the tumor site, and it provided exceptional tumor inhibition rate against liver cancer cells (>76%). Overall, our research presents a promising multifunctional theranostic nanoplatform for the development of synergistic therapeutics for tumors in further applications.

A smart dual-drug nanosystem based on co-assembly of plant and food-derived natural products for synergistic HCC immunotherapy.

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel "core‒shell" co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and "green" method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells in vitro, good biosafety of organic tissues and efficient tumor accumulation in vivo. Importantly, UA combined with EGCG showed the immunotherapy by activating the innate immunity and acquired immunity resulting in significant synergistic therapeutic effect. The research could provide new ideas for the research and development of self-assembly delivery system in the future, and offer effective intervention strategies for clinical HCC treatment.