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In this report, we present a mesoporous carbon nanosphere that can target drugs to tumors and image tumor biomarkers. A single-strand DNA (P0 aptamer) aptavalve was capped on the surface of doxorubicin-loaded oxide mesoporous carbon nanospheres (Dox-OMCN-P0) through π-π stacking for real-time imaging-guided on-demand targeting drug delivery. The Dox-OMCN-P0 could not only realize the detection of MUC1 tumor marker with a wide linear range (0.1 - 10.6 μmol/L) and a low detection limit (17.5 nmol) based on different apparatuses, but also achieve in-situ targeting imaging of cellular MUC1 concentration in vitro and in vivo via "off-on" fluorescence biosensing. Much attractively, as a real-time feedback of the diagnostic/imaging outcomes, Dox-OMCN-P0 accomplished the on-demand targeting drug delivery in quantitative response to MUC1. Controllable chemotherapy with sustained release and pH-sensitiveness, together with the potential photothermal therapy, were also clearly demonstrated. This is a simple but advanced platform, which could well achieve the real-time switchable imaging of cellular mucin for targeting cancer therapy.

mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence‐known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T‐cell receptor (TCR), CD134, and immune‐modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large‐scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA‐based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA‐based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA‐based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA‐based cancer immunotherapy are also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: The Shitou goose, derived from the swan goose (Anser cygnoides), is an excellent large goose breed in China and has high economic value. Therefore, it is imperative to delve into the study of its muscle characteristics. Circular RNA (CircRNA), acting as a molecular sponge, binds to miRNA, thereby intricately modulating targeted gene expression and influencing muscle growth and development. To unravel these complexities, we employed transcriptome sequencing to scrutinize the myoblasts and myotubes of Shitou geese, generating comprehensive circRNA and mRNA maps for two distinct developmental stages. In the subsequent analysis, a circRNA–miRNA–mRNA interaction network emerged, delineating a regulatory framework for muscle growth and development. This network is pivotal in understanding the underlying mechanisms of goose myogenesis and contributes new ideas and perspectives concerning the role of non-coding RNAs in the regulation of growth in geese. CircRNA, a recently characterized non-coding RNA (ncRNA) variant, functions as a molecular sponge, exerting regulatory control by binding to microRNA (miRNA) and modulating the expression of downstream proteins, either promoting or inhibiting their expression. Among poultry species, geese hold significant importance, prized by consumers for their delectable taste and rich nutritional content. Despite the prominence of geese, research on the growth and development of goose muscle, particularly the regulatory role of circRNAs in goose muscle formation, remains insufficiently explored. In this study, we constructed comprehensive expression profiles of circRNAs and messenger RNAs (mRNAs) within the myoblasts and myotubes of Shitou geese. We identified a total of 96 differentially expressed circRNAs (DEcircRNAs) and 880 differentially expressed mRNAs (DEmRNAs). Notably, the parental genes of DEcircRNAs and DEmRNAs exhibited enrichment in the Wnt signaling pathway, highlighting its potential impact on the proliferation and differentiation of goose myoblasts. Employing RNAhybrid and miRDB, we identified circRNA-miRNA pairs and mRNA-miRNA pairs that may play a role in regulating myogenic differentiation or muscle growth. Subsequently, utilizing Cytoscape, we constructed a circRNA–miRNA–mRNA interaction network aimed at unraveling the intricate regulatory mechanisms involved in goose muscle growth and development, which comprises 93 circRNAs, 351 miRNAs, and 305 mRNAs. Moreover, the identification of 10 hub genes (ACTB, ACTN1, BDNF, PDGFRA, MYL1, EFNA5, MYSM1, THBS1, ITGA8, and ELN) potentially linked to myogenesis, along with the exploration of their circRNA–miRNA–hub gene regulatory axis, was also conducted. These competitive endogenous RNA (ceRNA) regulatory networks elucidate the molecular regulatory mechanisms associated with muscle growth in Shitou geese, providing deeper insights into the reciprocal regulation of circRNA, miRNA, and mRNA in the context of goose muscle formation. [ABSTRACT FROM AUTHOR]

Calcium carbonate (CaCO3), a natural common inorganic material with good biocompatibility, low toxicity, pH sensitivity, and low cost, has a widespread use in the pharmaceutical and chemical industries. In recent years, an increasing number of CaCO3-based nano-drug delivery systems have been developed. CaCO3 as a drug carrier and the utilization of CaCO3 as an efficient Ca2+ and CO2 donor have played a critical role in tumor diagnosis and treatment and have been explored in increasing depth and breadth. Starting from the CaCO3-based nano-drug delivery system, this paper systematically reviews the preparation of CaCO3 nanoparticles and the mechanisms of CaCO3-based therapeutic effects in the internal and external tumor environments and summarizes the latest advances in the application of CaCO3-based nano-drug delivery systems in tumor therapy. In view of the good biocompatibility and in vivo therapeutic mechanisms, they are expected to become an advancing biomedicine in the field of tumor diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Carbon nanodots present resistance to photobleaching, bright photoluminescence, and superior biocompatibility, making them highly promising for bioimaging applications. Herein, nanoprobes were caged with four-armed oligomers and subsequently modified with a novel DBCO–PEG-modified retro-enantio peptide ligand reL57, enhancing cellular uptake into U87MG glioma cells highly expressing low-density lipoprotein receptor-related protein 1 (LRP1). A key point in the development of the oligomers was the incorporation of ε-amino-linked lysines instead of standard α-amino-linked lysines, which considerably extended the contour length per monomer. The four-armed oligomer 1696 was identified as the best performer, spanning a contour length of ~8.42 nm for each arm, and was based on an altering motive of two cationic ε-amidated lysine tripeptides and two tyrosine tripeptides for electrostatic and aromatic stabilization of the resulting formulations, cysteines for disulfide-based caging, and N-terminal azidolysines for click-modification. This work highlights that well-designed four-armed oligomers can be used for noncovalent coating and covalent caging of nanoprobes, and click modification using a novel LRP1-directed peptide ligand facilitates delivery into receptor-expressing target cells. [ABSTRACT FROM AUTHOR]

Chronic pain has attracted wide interest because it is a major obstacle affecting the quality of life. Consequently, safe, efficient, and low‐addictive drugs are highly desirable. Nanoparticles (NPs) with robust anti‐oxidative stress and anti‐inflammatory properties possess therapeutic possibilities for inflammatory pain. Herein, a bioactive zeolitic imidazolate framework (ZIF)‐8‐capped superoxide dismutase (SOD) and Fe3O4 NPs (SOD&Fe3O4@ZIF‐8, SFZ) is developed to achieve enhanced catalytic, antioxidative activities, and inflammatory environment selectivity, ultimately improving analgesic efficacy. SFZ NPs reduce tert‐butyl hydroperoxide (t‐BOOH)‐induced reactive oxygen species (ROS) overproduction, thereby depressing the oxidative stress and inhibiting the lipopolysaccharide (LPS)‐induced inflammatory response in microglia. After intrathecal injection, SFZ NPs efficiently accumulate at the lumbar enlargement of the spinal cord and significantly relieve complete Freund's adjuvant (CFA)‐induced inflammatory pain in mice. Moreover, the detailed mechanism of inflammatory pain therapy via SFZ NPs is further studied, where SFZ NPs inhibit the activation of the mitogen‐activated protein kinase (MAPK)/p‐65 signaling pathway, leading to reductions in phosphorylated protein levels (p‐65, p‐ERK, p‐JNK, and p‐p38) and inflammatory factors (tumor necrosis factor [TNF]‐α, interleukin [IL]‐6, and IL‐1β), thereby preventing microglia and astrocyte activation for acesodyne. This study provides a new cascade nanoenzyme for antioxidant treatments and explores its potential applications as non‐opioid analgesics. [ABSTRACT FROM AUTHOR]

CircRNAs are newly identified special endogenous RNA molecules that covalently close a loop by back-splicing with pre-mRNA. In the cytoplasm, circRNAs would act as molecular sponges to bind with specific miRNA to promote the expression of target genes. However, knowledge of circRNA functional alternation in skeletal myogenesis is still in its infancy. In this study, we identified a circRNA–miRNA–mRNA interaction network in which the axis may be implicated in the progression of chicken primary myoblasts' (CPMs) myogenesis by multi-omics (i.e., circRNA-seq and ribo-seq). In total, 314 circRNA–miRNA–mRNA regulatory axes containing 66 circRNAs, 70 miRNAs, and 24 mRNAs that may be relevant to myogenesis were collected. With these, the circPLXNA2-gga-miR-12207-5P-MDM4 axis aroused our research interest. The circPLXNA2 is highly differentially expressed during differentiation versus proliferation. It was demonstrated that circPLXNA2 inhibited the process of apoptosis while at the same time stimulating cell proliferation. Furthermore, we demonstrated that circPLXNA2 could inhibit the repression of gga-miR-12207-5p to MDM4 by directing binding to gga-miR-12207-5p, thereby restoring MDM4 expression. In conclusion, circPLXNA2 could function as a competing endogenous RNA (ceRNA) to recover the function of MDM4 by directing binding to gga-miR-12207-5p, thereby regulating the myogenesis. [ABSTRACT FROM AUTHOR]

Covalent organic framework (COF) receives great attention in biomedical applications due to its variable compositions and ordered structures. However, its targeted design to achieve desirable physiological functions especially for cancer treatments remains elusive. Herein, PEGylated COF with tumor‐specific TKD peptide modification is uniformly coated on photothermal mesoporous carbon nanospheres via polyethyleneimine‐mediated interface polymerization to construct a multifunctional core‐shell nanoparticle (OPCPT). Physicochemical studies demonstrate near infrared (NIR)‐blocking ability of the crystalline COF shells under physiological conditions, whereas COF is degraded under the acidic tumor microenvironments (TME). Subsequently, the nanoparticle charge is reversed and the COF monomers can produce 1O2/O2. As a result, OPCPT, activated in the TME due to the shell dissociation, penetrates deeply into tumors through positive charge‐mediated/lysosome rupture‐mediated transcytosis and recovers its NIR‐heating potential for tumor‐specific photothermal therapy. Moreover, the TME‐triggered 1O2 significantly depresses the lysosome autophagy via membrane destruction, and selectively damages the mitochondria to promote the cytochrome C release‐activated apoptosis and ATP deficiency‐inhibited tumor metastasis. Particularly, this unique O2 generation mechanism relieves the tumor hypoxia upon the reactive oxygen species therapy and downregulates hypoxia‐inducible factor and its downstream proteins, which all contribute to augmented tumor therapy. The findings represent a remarkable unveiling of the potential of COF‐based nanomaterials for extended biomedical applications. [ABSTRACT FROM AUTHOR]

The numerous biological barriers, which limit pharmacotherapy of pancreatic carcinoma, including inadequate drug accumulation in the tumor environment, a dense extracellular matrix (ECM) and efficient drug‐efflux mechanisms, illustrate the requirement of multifunctional delivery systems to overcome the individual barriers at the right place at the right time. Herein, a space–time conversion vehicle based on covalent organic framework (COF)‐coated mesoporous silica nanospheres (MSN) with a sandwiched polyethyleneimine (PEI) layer (MPCP), is designed. The space‐specific drugs‐loaded vehicle (MGPPCLP) is obtained by separately incorporating a chemotherapeutic agent (gemcitabine, G) into the MSN core, a P glycoprotein inhibitor (LY 335979, P) into the PEI layer, and an extracellular matrix disruptor (losartan, L) into the COF shell. Thereafter, a programmed drug delivery is achieved via the ordered degradation from COF shell to MSN core. Sequential release of the individual drugs, synergized with a change of nanoparticle surface charge, contribute to an obvious extracellular matrix distraction, distinct drug efflux inhibition, and consequently enhance chemotherapeutic outcomes in pancreatic carcinoma. This MPCP‐based vehicle design suggests a robust space–time conversion strategy to achieve programmed multi‐drugs delivery and represents a new avenue to the treatment of pancreatic carcinoma by overcoming extracellular matrix and drug reflux barriers. [ABSTRACT FROM AUTHOR]