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Comprehensive Summary: Tumor stroma composing diverse extracellular matrixes (ECM) and stromal cells shapes a condensed physical barrier, which severely hampers the efficient accessibility of nanomedicine to tumor cells, especially these deep‐seated in the core of tumor. Such barrier significantly compromises the antitumor effects of drug‐loaded nanomedicine, revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration ability. To achieve this goal, various nanoparticle‐based strategies have been developed, including direct depleting ECM components via delivering anti‐fibrotic agents or targeting stromal cells to suppress ECM expression, dynamic regulation of nanoparticles' physicochemical properties (i.e., size, surface charge, and morphology), mechanical force‐driven deep penetration, natural/biomimetic self‐driven nanomedicine, and transcytosis‐inducing nanomedicine. All these nanostrategies were systemically summarized in this review, and the design principles for obtaining admirable nanomedicine were included. With the rapid development of nanotechnology, elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies, such as chemotherapy, photodynamic therapy, and immunotherapy. Key Scientists: In 2006, Chan et al. demonstrated that the size and shape of nanoparticles were important for biomedical applications, such as intracellular delivery rate and tissue penetration. In addition, the degradation of the structural collagen was confirmed to increase the diffusion of nanoparticles and macromolecules by Davies et al. in 2010. These findings reveal the importance of chemophysical properties of nanoparticles in determining their diffusion and the critical roles of stromal barrier in hindering nanoparticles penetration. On the basis of this, photoswitchable nanoparticles were developed by Kohane et al. for triggered tissue penetration and efficient drug delivery. In 2015, Nie et al. reported the targeted depletion of cancer‐associated fibroblasts by peptide assembly for enhanced antitumor drug delivery. In 2019, Shen et al. proposed the transcytosis strategy to promote the tumor penetration of nanoparticles. Very recently, Luo et al. reported the specific reversing of the biological function of cancer‐associated fibroblasts to suppress the generation of stromal matrix, greatly increasing the drug perfusion in tumor tissue. All these strategies fueled the design and construction of function‐specific nanoparticles for tumor therapy. [ABSTRACT FROM AUTHOR]

The last decade witnessed the great advances in the development of nanomedicines. As a kind of attractive nanomedicine, carrier-free nanomedicines received extensive investigations because of their high biosafety, high drug loading capacities, simple drug compositions and simplified synthetic procedures. Extensive efforts have been made to exploit more excipients and therapeutic agents, new self-assembly methods and therapeutic mechanisms to expand the scope of carrier-free nanomedicines with enhanced therapeutic performance. In this review, we summarized the research progress of carrier-free nanomedicines with practical applications in cancer therapy. Carrier-free nanomedicines were classified into three kinds, including free drugs, prodrugs and non-drug agents based carrier-free nanomedicines. These carrier-free nanomedicines were introduced in detail according to their drug compositions, assembly and antitumor applications. The current clinical translation situation and safety of carrier-free nanomedicines were also summarized. The outlooks were included in the conclusion section to discuss the existing challenges on the future development and clinical application of carrier-free nanomedicines. [ABSTRACT FROM AUTHOR]

Abstract: To investigate the temperature sensitive mechanism and develop temperature sensitive materials, a novel poly(N-isopropyl-3-butenamide) (PNIPBAm) hydrogel was designed and synthesized. The maximum swelling ratio, temperature dependence of swelling ratio and deswelling/reswelling kinetics of the resulted PNIPBAm hydrogel were characterized. The data obtained exhibited that the temperature sensitivity of the PNIPBAm hydrogel depended on the amount of crosslinker, i.e. the temperature sensitivity decreased with the increasing content of crosslinker. This novel temperature sensitive hydrogel would have the potential applications in bioengineering and biotechnology fields. [Copyright &y& Elsevier]

A series of novel pH and thermosensitive hydrogels, comprised of N-isopropylacrylamide (NIPAAm) and N-isopropyl-maleamic acid (NIPMMA) units were designed and fabricated. The resultant P(NIPAAm-co-NIPMMA) hydrogels were characterized and it was found, with the increasing content of NIPMMA, that the pH sensitivity of P(NIPAAm-co-NIPMMA) hydrogel improved, whilst the temperature sensitivity remained almost the same. This unique intelligent character was attributed to the existence of a continuous isopropylamide sequence in P(NIPAAm-co-NIPMMA) hydrogels. [Copyright &y& Elsevier]

Abstract: An amphiphilic AB block copolymer composed of poly(N-isopropylacrylamide) as a hydrophilic segment and poly(10-undecenoic acid) as a hydrophobic segment was synthesized. Cytotoxicity study of this copolymer exhibited no significant cytotoxicity. The lower critical solution temperature (LCST) of the copolymer was 30.8 °C, as determined by the turbidity method. The block copolymer forms micelles in an aqueous medium at the temperature lower than the LCST. Transmission electron microscopy images showed that these micelles were regularly spherical in shape. The micelle size determined by size analysis was around 160 nm. The anti-inflammation drug prednisone acetate was incorporated into the micelles and the release profiles of prednisone acetate showed a dramatic thermoresponsive switching behavior and a unique pH responsive behavior. Moreover, the pH responsive behavior was in relation to the thermoresponsive behavior. That is, the micelles were not pH sensitive at the temperature below the LCST, but the aggregates were pH sensitive at the temperature above the LCST. Based on these results, the thermo- and pH responsive micelles have great potential to be a novel carrier for drug delivery. [Copyright &y& Elsevier]

Abstract: Fast responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with improved properties were prepared in phenol aqueous solutions with different concentrations. Due to the expanded network structure in water, the resulted hydrogels are capable of absorbing a large amount of water, i.e. exhibits a much increased swelling ratio at room temperature. Importantly, the hydrogels demonstrated much faster response rate than that of traditional PNIPAAm hydrogel upon external temperature increase. [Copyright &y& Elsevier]

Abstract: To achieve a combination of spatial specificity in a passive manner with a stimuli–response targeting mechanism, a temperature-responsive polymeric micelle was prepared using block copolymers of poly(N-isopropylacrylamide-b-methyl methacrylate) (PNIPAAm-b-PMMA). The critical micelle concentration of amphiphilic block copolymers in aqueous solution was determined by fluorescence spectroscopy using pyrene as a fluorescence probe. Transmission electron microscopy images showed that these nanoparticles were regularly spherical in shape. Micelle size determined by size analysis was around 190nm. The micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PNIPAAm at around 33°C, observed by optical absorbance measurements and dynamic light scattering (DLS). The anti-inflammation drug prednisone acetate was loaded as the model drug in the polymeric nanoparticles. In vitro release behavior of prednisone acetate was investigated, which showed a dramatic thermoresponsive fast/slow switching behavior according to the temperature-responsive structural changes of a micellar shell structure. The reversible and sensitive thermoresponse of this micelle might provide opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia. [Copyright &y& Elsevier]

Abstract: Poly(N-isopropylacrylamide)/poly(ethylene glycol) diacrylate (PNIPAAm/PEG-DA) microgels were used as an additive during the polymerization and/or crosslinking of PNIPAAm hydrogels to improve their thermosensitive properties. The influence of this additive on the property of resulting PNIPAAm hydrogels was investigated and characterized. The interior morphology by scanning electron microscopy (SEM) revealed that microgel impregnated PNIPAAm hydrogels have tighter and constrained porous network structures, although large cavities of 30–40μm in diameter, occupied by the microgels were sporadically distributed in this constrained network. Differential scanning calorimetry (DSC) studies did not show apparent difference in lower critical solution temperature (LCST) between normal and microgel-impregnated PNIPAAm hydrogels. The incorporating of PNIPAAm/PEG-DA microgels, however, significantly improved mechanical properties of modified hydrogels when comparing with a normal PNIPAAm hydrogel, although the tendency was not strictly proportional to the microgel amount. Based on the temperature-induced swelling ratio data as well as response kinetics, microgel-impregnated hydrogels exhibited improved thermosensitive characteristics in terms of higher equilibrium swelling ratio as well as faster response rates and the level of improvement depended on the amount of microgel impregnated. [Copyright &y& Elsevier]

Abstract: In this contribution, a novel smart drug delivery system (DDS) consisting of hydroxyl-functionalized glycerol poly(ɛ-caprolactone) (PGCL)-based microspheres and poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was developed for prolonged and sustained controlled drug release. Various amounts PGCL-based microspheres were incorporated physically into temperature sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel to form the novel DDSs. Resulting DDSs were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and compression modulus measurements to investigate the morphological, thermal, and mechanical properties. The temperature dependence of swelling ratio and response kinetics upon heating or cooling were also investigated to understand the smart properties, i.e., temperature sensitive properties of these DDSs. Finally, ovalbumin (OVA), used as the model drug, was loaded into PGCL-based microspheres to examine and compare the effects of controlled release at different temperature (22 and 37°C) of these novel smart DDSs. [Copyright &y& Elsevier]

Objective: To develop and characterize a new class of temperature-sensitive hydrogel microspheres composed of poly(N-isopropylacrylamide)/poly(ethylene glycol) diacrylate (PNIPAAm/PEG-DA). Methods: The PNIPAAm/PEG-DA hydrogel microspheres were fabricated in two aqueous systems as a result of polymer/polymer immiscibility. Both PNIPAAm and PEG-DA were used as the precursors; the PEG-DA was also used as a cross-linker for the formation of the hydrogel microspheres. Bovine serum albumin was used as the model protein drug to examine the effects of the thermo-responsive properties of the hydrogel microspheres on the release of a protein at two different temperatures (22°C and 37°C). Results: The hydrated PNIPAAm/PEG-DA hydrogel microspheres exhibited a swollen diameter of 50µm, with a narrow particle-size distribution. Scanning electron microscopy and environmental scanning electron microscopy observations revealed that, upon swelling, the resulting hydrogel microspheres had a regular spherical and rough surface morphology. The lower critical solution temperature (LCST) of the PNIPAAm/PEG-DA hydrogel microspheres was around 29.1°C, based on differential scanning calorimetric data. The release of BSA from the hydrogel microspheres at 37°C was slower than that at 22°C because of the thermo-responsive nature of PNIPAAm at temperatures above its LCST. Conclusions: We believe that these kinds of PNIPAAm/PEG-DA hydrogel microspheres may have wide applications as promising drug delivery systems, because of their intelligent nature upon external temperature change. [ABSTRACT FROM AUTHOR]

The development of a new temperature sensitive hydrogel particle having biodegradable crosslinkages, composed of poly(N-isopropylacrylamide)/dextran-allyl isocyanate (PNIPAAm/Dex-AI) was prepared through precipitation polymerization. Dex-AI was used as a precursor as well as a biodegradable crosslinker for forming the network particles. Characterization data showed that these PNIPAAm/Dex-AI hydrogel particles had an average hydration diameter around 1.0 mm and showed a dendrite-like heterogeneous morphology with two different porous microstructures. The hydrogel particles exhibited a transition temperature or lower critical solution temperature (LCST) at around 25.7 °C through differential scanning calorimetry (DSC) measurement or temperature dependence study of particles volume. The freeze-dried particles swelled quickly when socked in distilled water at room temperature and large amounts of water were stored within the network before reaching the stable swollen state. [Copyright &y& Elsevier]

A method was developed to prepare thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with an interpenetrating polymer network (IPN) structure for the purpose of improving its mechanical properties, response rate to temperature and sustained release of drugs. Although the differential scanning calorimetry data exhibited similarly lower critical solution temperature (LCST) between IPN- and non-IPN–PNIPAAm hydrogels, an increase in the glass transition temperature (Tg) of the IPNs relative to the normal PNIPAAm hydrogel was observed. In addition, the mechanical properties of the IPNs were greatly improved when compared with the normal PNIPAAm hydrogel. The interior morphology of the IPN–PNIPAAm hydrogels was revealed by scanning electron microscopy (SEM); the IPN hydrogels showed a fibrillar-like porous network structure that normal PNIPAAm did not have. Furthermore, by measuring the temperature dependence of the swelling ratio and deswelling kinetics, these IPN hydrogels also exhibited improved intelligent characteristics (e.g., controllable faster response rate) that depended on the composition ratio of the two network components. From the applications viewpoint, the effects of a shrinking–reswelling cycle around the LCST on the properties of the IPN hydrogels were examined to determine if these properties would be stable for potential applications. Bovine serum albumin was chosen as the model protein for examining its release from the IPNs at different temperatures. The release data suggested that an improved controlled release could be achieved by the IPN–PNIPAAm hydrogels without losing their intelligent properties. [Copyright &y& Elsevier]

The model drug, 5-fluorouracil (5-FU) was loaded into the poly(N-isopropylacrylamide) (PNIPA) hydrogel at 25 °C, then the drug-loaded, swollen hydrogel sample was carefully enveloped in the dialysis bag to form a novel thermo-responsive drug delivery system (DDS). The concentration of released 5-FU was monitored at 266 nm on the UV spectrophotometer. We found that this novel DDS provides a positive drug release pattern and the drug, 5-FU, was released faster at the increased temperature (37 °C, >25 °C) than the one at the decreased temperature (10 °C, <25 °C). This was attributed to the double control of the thermo-sensitivity of the hydrogel matrix and the dialysis membrane. By employing the fast response PNIPA hydrogel instead of the conventional hydrogel in this novel DDS, we can further control the drug release rate and/or drug release amount etc., without changing the positive, thermo-responsive drug release pattern. [Copyright &y& Elsevier]

Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel exhibits a response to external temperature variation and shrinks in volume abruptly as the temperature is increased above its lower critical solution temperature. It has great potential applications in biomedical fields. A rapid response rate is essential, especially when this material is designed as an on–off switch for targeted drug delivery. However, due to the appearance of a thick, dense skin layer on the hydrogel surface during the shrinking process, the deswelling rate of conventional PNIPAAm gels is low. In this article, a novel method is proposed to modify the surface morphology of PNIPAAm gel, in which the swollen gels are frozen at low temperature (−20°C). The scanning electron micrographs revealed that a fishnet-like skin layer appeared on the surfaces of the cold-treated gels. Dramatically rapid deswelling was achieved with the cold-treated gels since the fishnet-like structure with numerous small pores prevented the formation of a dense, thick skin layer during the deswelling process, which commonly occurs in normal PNIPAAm hydrogels. Prolonging the cold treatment from 1 day to 10 days resulted in a slightly higher deswelling rate. Rearrangement of the hydrogel matrix structure during the freezing process might contribute to the formation of the fishnet-like skin layer. The water uptake of the hydrogels increased nearly in proportion to the square root of time, indicating that the reswelling rate of hydrogels was controlled predominantly by water diffusion into the network. However, there were no significant differences in the equilibrated swelling ratio and reswelling kinetics at room temperature (22°C) between normal gels and cold-treated gels, which implied that cold treatment did not change bulk porosity and gel tortuosity much. [Copyright &y& Elsevier]

Paraptosis is a non‐apoptotic and caspase‐independent programmed cell death that can trigger immunogenic cell death (ICD) in tumor cells, representing a potent tactic to overcome immune tolerance to apoptosis. Here, this study demonstrates the construction of a dual‐responsive nanoreactor (MCGDH) to achieve paraptosis‐mediated ICD for chemo‐immunotherapy. Specifically, by doping Cu2+ into glutathione (GSH)‐responsive dendritic mesoporous silica nanoparticles, the platform (CGDMSN) is endowed with partial acid‐sensitivity. After loaded with 8‐hydroxyquinoline (8‐HQ), cell membrane fragments are coated onto the ammoniated CGDMSN surface to construct MCGDH. Upon internalization by tumor cells, the release of Cu2+ and 8‐HQ from MCGDH in response to the acidic pH and high concentration of GSH in the tumor microenvironment stimulates in situ generation of Cu(8‐HQ)2, inducing tumor cells paraptosis at a low copper dose. Moreover, MCGDH‐mediated paraptosis amplifies the immunogenicity of tumor cells, facilitating antigen presentation to dendritic cells and activating CD8+/CD4+ T cells immune responses. Furthermore, the combination of MCGDH and anti‐PD‐1 antibodies (αPD‐1) promotes the systemic anti‐tumor immune responses and long‐term immunological effect to vastly inhibit the primary/distant tumor growth and prevent tumor metastasis. This GSH/pH dual‐responsive nanoreactor serves as a selective platform for accelerating the development of chemo‐immunotherapy. [ABSTRACT FROM AUTHOR]

A microalgal oxygenerator (PTA) was developed by surface coating microalgae with the photothermal agent polydopamine. The PTA is capable of generating O 2 in situ within the tumor through photosynthesis. This process effectively targets the hypoxia-adenosine axis, thereby reducing immunosuppression. The modification of the tumor microenvironment promotes antitumor immunity triggered by photothermal therapy and significantly improves antitumor efficiency. [Display omitted] Hypoxia induces the generation of immunosuppressive adenosine within the tumor microenvironment (TME) and further impedes the activation of antitumor immunity triggered by photothermal therapy (PTT). In this study, a photothermal microalgae system (PTA) based on Chlorella sorokiniana (C. soro) is developed to boost antitumor immune responses by targeting the hypoxia-adenosine axis. PTA is constructed by coating polydopamine (PDA), a promising photothermal agent with good biocompatibility, on the surface of C. soro. Due to the inherent photosynthetic capability of microalgae, PTA in situ generates O 2 within the tumor under irradiation at 660 nm for hypoxia alleviation, thereby downregulating the level of adenosine to reverse the immunosuppression in TME. Subsequently, this reshaped TME promotes the activation of antitumor immunity induced by PTT, which is realized by the coated PDA layer on C. soro under irradiation at 808 nm. In a mouse model of 4T1 tumors, PTA significantly weakens the immunosuppression in the TME, elicits robust antitumor immune responses, and suppresses tumor growth. Together, this strategy highlights the potential of leveraging living photosynthetic microalgae as an oxygenerator to boost cancer photothermal immunotherapy. [ABSTRACT FROM AUTHOR]

The lack of broad‐spectrum tumor antigens, limited immunogenicity of antigens, and immunosuppressive microenvironment in tumors have impeded the development of cancer vaccines. To address this issue, a vaccine platform is developed based on Spirulina skeleton fibers loaded with gold (Au) nanoparticles (Au@E‐SP). Upon subcutaneous administration, Au@E‐SP self‐aggregates in situ and forms a 3D vaccine scaffold owing to its elongated and helical architecture. Through the aggregation of Au@E‐SP, Au nanoparticles are concentrated, which significantly enhances the local photothermal effect and releases more tumor‐associated antigens. In addition, the retained E‐SP serves as a natural immune adjuvant that sustainably reverses the immunosuppressive microenvironment in vivo. Combining these advantages, the vaccines induce a potent anti‐tumor immune response, effectively inhibiting tumor recurrence and metastasis. This strategy utilizes microalgae as a self‐adjuvant vaccine, providing a promising avenue for further research in tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Cancer has been the most deadly disease, and 13 million cancer casualties are estimated to occur each year by 2030. Gold nanoparticles (AuNPs)‐based photothermal therapy (PTT) has attracted great interest due to its high spatiotemporal controllability and noninvasiveness. Due to the trade‐off between particle size and photothermal efficiency of AuNPs, rational design is needed to realize aggregation of AuNPs into larger particles with desirable NIR adsorption in tumor site. Exploiting the bioorthogonal "Click and Release" (BCR) reaction between iminosydnone and cycloalkyne, aggregation of AuNPs can be achieved and attractively accompanied by the release of chemotherapeutic drug purposed to photothermal synergizing. We synthesize iminosydnone‐lonidamine (ImLND) as a prodrug and choose dibenzocyclooctyne (DBCO) as the trigger of BCR reaction. A PEGylated AuNPs‐based two‐component nanoplatform consisting of prodrug‐loaded AuNPs‐ImLND and tumor‐targeting peptide RGD‐conjugated AuNPs‐DBCO‐RGD is designed. In the therapeutic regimen, AuNPs‐DBCO‐RGD are intravenously injected first for tumor‐specific enrichment and retention. Once the arrival of AuNPs‐ImLND injected later at tumor site, highly photothermally active nanoaggregates of AuNPs are formed via the BCR reaction between ImLND and DBCO. The simultaneous release of lonidamine further enhanced the therapeutic performance by sensitizing cancer cells to PTT. [ABSTRACT FROM AUTHOR]

Cancer has been the most deadly disease, and 13 million cancer casualties are estimated to occur each year by 2030. Gold nanoparticles (AuNPs)‐based photothermal therapy (PTT) has attracted great interest due to its high spatiotemporal controllability and noninvasiveness. Due to the trade‐off between particle size and photothermal efficiency of AuNPs, rational design is needed to realize aggregation of AuNPs into larger particles with desirable NIR adsorption in tumor site. Exploiting the bioorthogonal "Click and Release" (BCR) reaction between iminosydnone and cycloalkyne, aggregation of AuNPs can be achieved and attractively accompanied by the release of chemotherapeutic drug purposed to photothermal synergizing. We synthesize iminosydnone‐lonidamine (ImLND) as a prodrug and choose dibenzocyclooctyne (DBCO) as the trigger of BCR reaction. A PEGylated AuNPs‐based two‐component nanoplatform consisting of prodrug‐loaded AuNPs‐ImLND and tumor‐targeting peptide RGD‐conjugated AuNPs‐DBCO‐RGD is designed. In the therapeutic regimen, AuNPs‐DBCO‐RGD are intravenously injected first for tumor‐specific enrichment and retention. Once the arrival of AuNPs‐ImLND injected later at tumor site, highly photothermally active nanoaggregates of AuNPs are formed via the BCR reaction between ImLND and DBCO. The simultaneous release of lonidamine further enhanced the therapeutic performance by sensitizing cancer cells to PTT. [ABSTRACT FROM AUTHOR]

Tumor recurrence and unfavorable bacterial biofilm formation on implants after bone tumor resection remain challenging in clinical settings. However, this dilemma also provides inspiration for the development of bioactive implants and a new route for the management of bone tumors through biofilm formation. Here, based on the characteristic that bacteria prefer to adhere to implants, 3D‐printing bioceramic scaffolds modified with probiotic biofilms are designed to augment antitumor immunity. In comparison with Akkermansia muciniphila, Lactobacillus rhamnosus GG (LGG) is demonstrated to more easily form biofilms on bioceramics and is selected to engineer etched bioceramics. The LGG biofilm subjected to pasteurization guarantees good biocompatibility and enhanced doxorubicin (Dox) loading. Furthermore, the LGG biofilm combined with Dox imparts the scaffolds with multiple properties of direct chemo‐killing for tumor cells and potent immune activation. The modified scaffolds efficiently inhibit bone tumor recurrence and bone metastasis in murine tumor model receives surgical resection. Moreover, based on 3D‐printing technology, the probiotic biofilm modified scaffolds with adjustable shapes are also demonstrated to repair shape‐specific bone defects after tumor elimination. Collectively, the multifunctional 3D‐printing scaffolds realize the integrated treatment of tumor elimination and bone repair, providing a promising strategy for clinical treatment of bone tumors. [ABSTRACT FROM AUTHOR]

A critical challenge of existing cancer vaccines is to orchestrate the demands of antigen‐enriched furnishment and optimal antigen‐presentation functionality within antigen‐presenting cells (APCs). Here, a complementary immunotherapeutic strategy is developed using dendritic cell (DC)‐tumor hybrid cell‐derived chimeric exosomes loaded with stimulator of interferon genes (STING) agonists (DT‐Exo‐STING) for maximized tumor‐specific T‐cell immunity. These chimeric carriers are furnished with broad‐spectrum antigen complexes to elicit a robust T‐cell‐mediated inflammatory program through direct self‐presentation and indirect DC‐to‐T immunostimulatory pathway. This chimeric exosome‐assisted delivery strategy possesses the merits versus off‐the‐shelf cyclic dinucleotide (CDN) delivery techniques in both the brilliant tissue‐homing capacity, even across the intractable blood–brain barrier (BBB), and the desired cytosolic entry for enhanced STING‐activating signaling. The improved antigen‐presentation performance with this nanovaccine‐driven STING activation further enhances tumor‐specific T‐cell immunoresponse. Thus, DT‐Exo‐STING reverses immunosuppressive glioblastoma microenvironments to pro‐inflammatory, tumoricidal states, leading to an almost obliteration of intracranial primary lesions. Significantly, an upscaling option that harnesses autologous tumor tissues for personalized DT‐Exo‐STING vaccines increases sensitivity to immune checkpoint blockade (ICB) therapy and exerts systemic immune memory against post‐operative glioma recrudesce. These findings represent an emerging method for glioblastoma immunotherapy, warranting further exploratory development in the clinical realm. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) are an emerging kind of crystalline porous polymers that present the precise integration of organic building blocks into extensible structures with regular pores and periodic skeletons. The diversity of organic units and covalent linkages makes COFs a rising materials platform for the design of structure and functionality. Herein, recent research progress in developing COFs for photoluminescent materials is summarised. Structural and functional design strategies are highlighted and fundamental problems that need to be solved are identified, in conjunction with potential applications from perspectives of photoluminescent materials. [ABSTRACT FROM AUTHOR]

Controlled nano-systems for drug delivery are designed to deliver therapeutical drugs to desirable sites on demand. Due to the diverse physiological functions of peptides, it is reasonable to introduce peptides into anti-tumor nano-system. The integration of peptides into nanomaterials has complementary advantages, which not only avoids the rapid degradation of peptides in vivo, but also improves the intelligence and functionality of the nano-system. We summarized the functional peptides with targeting and stimulus-responsive properties, and the present review outlined the most relevant and recent developed peptide-based multifunctional nanomaterials for tumor therapy. Unlabelled Image [ABSTRACT FROM AUTHOR]

Controlled nano-systems for drug delivery are designed to deliver therapeutical drugs to desirable sites on demand. Due to the diverse physiological functions of peptides, it is reasonable to introduce peptides into anti-tumor nano-system. The integration of peptides into nanomaterials has complementary advantages, which not only avoids the rapid degradation of peptides in vivo, but also improves the intelligence and functionality of the nano-system. We summarized the functional peptides with targeting and stimulus-responsive properties, and the present review outlined the most relevant and recent developed peptide-based multifunctional nanomaterials for tumor therapy. Unlabelled Image [ABSTRACT FROM AUTHOR]

We found CRC is sensitive to cuproptosis which also results in IFN-γ-inducible PD-L1 upregulation in tumor cells. A cuproptosis-mediated immunotherapy nanoreactor is constructed for CRC treatment. It not only significantly induces cuproptosis in cancer cells, but also initiates cuproptosis-mediated systemic immune responses, reshapes immunosuppressive TME and prevents immune evasion, further inhibiting both primary and distant tumor growth. [Display omitted] Owing to the deficiency of infiltrating immune cells and the accumulation of immunosuppressive cells in tumor microenvironment (TME), immunotherapy remains enormous challenges in colorectal cancer (CRC). Here, CRC was found to be sensitive to cuproptosis which could further evoke immune responses and mediate immune resistance. Thus, a cuproptosis-mediated immunotherapy nanoreactor (CCJD-FA) was constructed by encapsulating copper-based shell-coated CaO 2 and bromodomain-containing protein 4 inhibitor JQ-1 with DSPE-PEG-FA. Within tumor cells, CCJD-FA was disassembled under GSH environment, and the exposed CaO 2 could generate H 2 O 2 under the acidic condition, which reacted with the released Cu2+ via Fenton-like reaction to produce O 2 for relieving hypoxia and Cu+ for inducing cuproptosis. Furthermore, CCJD-FA could also inhibit intracellular glycolysis and ATP generation, then blocking the Cu+ efflux protein ATP7B. Meanwhile, the IFN-γ-induced PD-L1 expression could be exactly reduced by the BRD4 suppression and oxygen supply. These effects sensitized cancer cells to cuproptosis, further evoking systemic immune responses and reshaping immunosuppressive TME to inhibit tumor growth. [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) induced by specific chemotherapeutic agents is often hampered by the immunosuppressive tumor microenvironment (TME). Here, a bacterial bioreactor E@Fe‐DOX, is developed, to enhance ICD‐mediated antitumor immunity by in situ manipulation of tumor metabolism‐immune interactions. The E@Fe‐DOX bioreactor is constructed by depositing doxorubicin‐loaded iron‐polyphenol nanoparticles on Eubacterium hallii, which can specifically target hypoxic tumor regions and release doxorubicin and Fe3+ to induce ICD. In addition, Eubacterium hallii can continuously convert intratumoral lactate to butyrate, which inhibits the polarization of pro‐tumoral M2‐like macrophages and improves the function of tumor‐infiltrating cytotoxic T cells. Furthermore, E@Fe‐DOX promotes the formation of immune cell‐aggregated tertiary lymph structures (TLS) to augment ICD‐induced antitumor immunity. In murine tumor models, E@Fe‐DOX significantly inhibits tumor growth and enhances immune checkpoint blockade (ICB) therapy. Overall, the developed living biomaterial offers a promising strategy to potentiate cancer chemo‐immunotherapy by continuously regulating the intratumoral immuno‐metabolic microenvironment. [ABSTRACT FROM AUTHOR]

Biofilms are the chief culprits of most intractable infections and pose great threat to human health. Developing effective strategies to sweep away the detrimental microbe and stubborn biofilm still remains a challenge. Here, an ultrasound (US) activated microbomb is constructed by encapsulating perfluorohexane (PFH) and iron‐tannin modified calcium peroxide (CaO2‐TA‐Fe) in poly(lactide‐co‐glycolide) (PLGA) vesicles as the reactive oxygen species (ROS) generating reactors for dental biofilm elimination. Upon the US irradiation by ultrasonic toothbrush, the swiftly vaporized PFH can not only promptly explode the PLGA shell to facilitate the generation of H2O2 from CaO2, but also blast the tight biofilm for effective delivery of the lethal hydroxyl free radicals (•OH) caused by degradative Fe3+ from iron‐tannin network, thereby proceeding cascade catalysis eradication of biofilm. As a proof‐of‐concept, this study demonstrates the proposed synergetic paradigm that integrates the US‐triggered explosion with ROS‐induced sterilization for stubborn biofilm elimination, and is a promising tactic for the costly and prevalent caries prevention as well as the biofilm‐associated diseases treatments. [ABSTRACT FROM AUTHOR]

Attempting to couple photochemical CO2 reduction with N2 fixation is usually difficult, because the reaction conditions for these two processes are typically incompatible. Here, we report that a light-driven biohybrid system can utilize abundant, atmospheric N2 to produce electron donors via biological nitrogen fixation, to achieve effective photochemical CO2 reduction. This biohybrid system is constructed by incorporating molecular cobalt-based photocatalysts into N2-fixing bacteria. It is found that N2-fixing bacteria can convert N2 into reductive organic nitrogen and create a localized anaerobic environment, which allows the incorporated photocatalysts to continuously perform photocatalytic CO2 reduction under aerobic conditions. Specifically, the light-driven biohybrid system displays a high formic acid production rate of over 1.41 × 10−14 mol h−1 cell−1 under visible light irradiation, and the organic nitrogen content undergoes an over-3-fold increase within 48 hours. This work offers a useful strategy for coupling CO2 conversion with N2 fixation under mild and environmentally benign conditions. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ) is an oral DNA-alkylating drug used in colorectal cancer (CRC) chemotherapy. In this work, we proposed a safe and biomimetic platform for macrophages-targeted delivery of TMZ and O6-benzylguanine (O6-BG). TMZ was loaded in poly (D, l -lactide-coglycolide) (PLGA) nanoparticles, followed by sequential coating with O6-BG-grafted chitosan (BG-CS) layers and yeast shell walls (YSW) via layer-by-layer assembly (LBL) process, forming TMZ@P-BG/YSW biohybrids. Due to the yeast cell membrane-camouflage, TMZ@P-BG/YSW particles exhibited significantly enhanced colloidal stability as well as low premature drug leakage in simulated gastrointestinal conditions. In vitro drug release profiles of TMZ@P-BG/YSW particles revealed noticeable higher TMZ release in simulated tumor acidic environment within 72 h. Meanwhile, O6-BG could down-regulate MGMT expression in CT26 colon carcinoma cells, ultimately facilitating TMZ-induced tumor cell death. After oral delivery of yeast cell membrane-camouflaged particles containing fluorescent tracer (Cy5), TMZ@P-BG/YSW and bare YSW displayed high retention time of 12 h in the colon and small intestine (ileum). Correspondingly, oral gavage administration of TMZ@P-BG/YSW particles afforded favorable tumor-specific retention and superior tumor growth inhibition. Overall, TMZ@P-BG/YSW is validated to be a safe, targetable and effective formulation, paving a new avenue towards highly effective and precise treatment of malignancies. PLGA-based bioinspired platform for tumor-specific retention and enhanced colorectal cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

B cell activating factor (BAFF) has been shown to play a key role in regulating B cell function, but little is known about whether BAFF affects the function of fibroblast-like synoviocyte (FLS), an effector cell of rheumatoid arthritis (RA). CP-25, a new ester derivative of paeoniflorin, could alleviate the arthritis symptoms of collagen-induced arthritis (CIA) mice by inhibiting BAFF-mediated abnormal activation of B cells. In this study, we aimed to understand the mechanism by which BAFF activates FLS and the effect of CP-25 on FLS function. Therefore, the proliferation and migration abilities of FLS and key proteins on the non-canonical NF-κB pathway were examined. The results showed that compared with the FLS of normal rats/OA patients, the expression of BAFF-R, TRAF2, NIK, p-IKKα, P100, and P52 was higher in the FLS of AA rats/RA patients, while the expression of TRAF3 was lower. And, BAFF promotes FLS activation by activating the non-canonical NF-κB signaling pathway. Meanwhile, BAFFR-siRNA inhibited the proliferation of FLS and the activation of non-canonical NF-κB signaling in FLS induced by BAFF. Additionally, CP-25 could inhibit abnormal proliferation and migration of FLS by regulating non-canonical NF-κB signaling. We concluded that BAFF may act as an important role in facilitating the function of FLS through the BAFFR-mediated non-canonical NF-κB pathway, which would be useful for revealing the pathological mechanism of RA. And CP-25 may become a potential new drug for the treatment of RA, providing a scientific basis for the development of new drugs to treat RA. [ABSTRACT FROM AUTHOR]

The endogenous H 2 S plays an important role in the occurrence and development of colon cancer, and is related to the abnormal blood vessels. Here, we reported on a sulfhydryl hyaluronid-based hydrogel (HA-SH) synthesized by amide reaction and further obtained a bacterial hydrogel by loading Thiobacillus denitrificans to the hydrogel for targeting adhesion to the colon. It was found that the loaded bacteria in HA-SH hydrogel can scavenge excess H 2 S in colon cancer, then promote tumor vascular normalization and improve the delivery of chemotherapy drug CPT to inhibit tumor progression. Both in vivo and in vitro experiments show that the self-crosslinked bacterial hydrogel has satisfactory effects in inhibiting tumor progression and promoting tumor vascular normalization in colon cancer. This study presents an efficient method to target the colon and consume overexpressed H 2 S in colon cancer to inhabit tumor progression, providing a new way for oral drug treatment of colon cancer. [Display omitted] • A bacterial hydrogel based on sulfhydrylated hyaluronic acid is reported. • Bacterial hydrogel targeting colon cancer consumes H 2 S. • Bacterial hydrogel consumes H 2 S to promote tumor vascular normalization. • Bacterial hydrogel improves chemotherapy of colon cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway could effectively initiate antitumor immunity, but specific activation of STING pathway is still an enormous challenge. Herein, a ferroptosis-induced mitochondrial DNA (mtDNA)-guided tumor immunotherapy nanoplatform (designated as HBMn-FA) was elaborately developed for activating and boosting STING-based immunotherapy. On the one hand, the high-levels of reactive oxygen species (ROS) in tumor cells induced by HBMn-FA-mediated ferroptosis elicited mitochondrial stress to cause the release of endogenous signaling mtDNA, which specifically initiate cGAS-STING pathway with the cooperation of Mn2+. On the other hand, the tumor-derived cytosolic double-stranded DNA (dsDNA) from debris of death cells caused by HBMn-FA further activated the cGAS-STING pathway in antigen-presenting cells (e.g., DCs). This bridging of ferroptosis and cGAS-STING pathway could expeditiously prime systemic antitumor immunity and enhance the therapeutic efficacy of checkpoint blockade to suppress tumor growth in both localized and metastatic tumor models. The designed nanotherapeutic platform paves the way for novel tumor immunotherapy strategies that are based on specific activation of STING pathway. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, a poor tissue penetration of activation light and low target specificity seriously hindered the clinical application of PDT. Here, we designed and constructed a size-controllable nanosystem (UPH) with inside-out responsive for deep PDT with enhanced biosafety. To obtain nanoparticles with the best quantum yield, a series of core-shell nanoparticles (UCNP@nPCN) with different thicknesses were synthesized by a layer-by-layer self-assembly method to incorporate a porphyritic porous coordination network (PCN) onto the surface of upconverting nanoparticles (UCNPs), followed by coating with hyaluronic acid (HA) on the surface of nanoparticles with optimized thickness to form the UPH nanoparticles. With the aid of HA, the UPH nanoparticles were capable of preferentially enriching in tumor sites and specific endocytosis by CD44 receptors as well as responsive degradation by hyaluronidase in cancer cells after intravenous administration. Subsequently, after being activated by strong penetrating 980 nm near-infrared light (NIR), the UPH nanoparticles efficiently converted oxygen into strongly oxidizing reactive oxygen species based on the fluorescence resonance energy transfer (FRET) effect, thereby significantly inhibiting tumor growth. Experimental results in vitro and in vivo indicated that such dual-responsive nanoparticles successfully realize the photodynamic therapy of deep-seated cancer with negligible side effects, which showed great potential for potential clinical translational research. [ABSTRACT FROM AUTHOR]

Probiotic spore germinator-based living biotherapeutics capable of specifically inhibiting Enterobacteriaceae growth and relieving acute colitis as well as colibactin-induced colonic cancerization was reported, which may propose a paradigm on gastrointestinal tract disease therapy by restoring gastrointestinal microenvironment. [Display omitted] The abnormal intestinal features like increased epithelial oxygenation, elevated inflammatory cascades and excess nitrate production can exacerbate colitis progression and even trigger colorectal cancer by promoting gut microbiota dysbiosis. Here, probiotic spores decorated with anti-inflammatory curcumin are encapsulated into cysteine-modified konjac glucomannan microspheres, to intervene colitis and colonic cancerization through remodeling gut microenvironment. Benefiting from the prolonged intestinal retention effect of polysaccharide microspheres, epithelial oxygenation is effectively restored into hypoxia in colon location due to spore germination-induced oxygen consumption, which blunts luminal Enterobacteriaceae overgrowth, and facilitates short chain fatty acids (SCFAs)-producing bacteria. By fermenting prebiotics of konjac glucomannan, the produced butyrate by SCFAs-producing bacteria further converts cell energy metabolism from glycolysis to oxygen-consumed β-oxidation by activating epithelial peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling, resulting in thorough oxygen outage, nitrate production-related enzymes downregulation and inflammatory response elimination. In view of directed gut microbiota modulation and colonic epithelial cell functions normalization, the potent intervention effect of spore germinator-loaded polysaccharide microspheres is achieved in multiple colitis models and genotoxic colibactin-producing Enterobacteriaceae - induced colon tumorigenesis. [ABSTRACT FROM AUTHOR]

Systematic administration of antibiotics to treat infections often leads to the rapid evolution and spread of multidrug‐resistant bacteria. Here, an in situ‐formed biotherapeutic gel that controls multidrug‐resistant bacterial infections and accelerates wound healing is reported. This biotherapeutic gel is constructed by incorporating stable microbial communities (kombucha) capable of producing antimicrobial substances and organic acids into thermosensitive Pluronic F127 (polyethylene‐polypropylene glycol) solutions. Furthermore, it is found that the stable microbial communities‐based biotherapeutic gel possesses a broad antimicrobial spectrum and strong antibacterial effects in diverse pathogenic bacteria‐derived xenograft infection models, as well as in patient‐derived multidrug‐resistant bacterial xenograft infection models. The biotherapeutic gel system considerably outperforms the commercial broad‐spectrum antibacterial gel (0.1% polyaminopropyl biguanide) in pathogen removal and infected wound healing. Collectively, this biotherapeutic strategy of exploiting stable symbiotic consortiums to repel pathogens provides a paradigm for developing efficient antibacterial biomaterials and overcomes the failure of antibiotics to treat multidrug‐resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Tumor hypoxia greatly suppresses the therapeutic efficacy of photodynamic therapy (PDT), mainly because the generation of toxic reactive oxygen species (ROS) in PDT is highly oxygen-dependent. In contrast to ROS, the generation of oxygen-irrelevant free radicals is oxygen-independent. A new therapeutic strategy based on the light-induced generation of free radicals for cancer therapy is reported. Initiator-loaded gold nanocages (AuNCs) as the free-radical generator were synthesized. Under near-infrared light (NIR) irradiation, the plasmonic heating effect of AuNCs can induce the decomposition of the initiator to generate alkyl radicals (R.), which can elevate oxidative-stress (OS) and cause DNA damages in cancer cells, and finally lead to apoptotic cell death under different oxygen tensions. As a proof of concept, this research opens up a new field to use various free radicals for cancer therapy. [ABSTRACT FROM AUTHOR]

Tumor hypoxia greatly suppresses the therapeutic efficacy of photodynamic therapy (PDT), mainly because the generation of toxic reactive oxygen species (ROS) in PDT is highly oxygen-dependent. In contrast to ROS, the generation of oxygen-irrelevant free radicals is oxygen-independent. A new therapeutic strategy based on the light-induced generation of free radicals for cancer therapy is reported. Initiator-loaded gold nanocages (AuNCs) as the free-radical generator were synthesized. Under near-infrared light (NIR) irradiation, the plasmonic heating effect of AuNCs can induce the decomposition of the initiator to generate alkyl radicals (R.), which can elevate oxidative-stress (OS) and cause DNA damages in cancer cells, and finally lead to apoptotic cell death under different oxygen tensions. As a proof of concept, this research opens up a new field to use various free radicals for cancer therapy. [ABSTRACT FROM AUTHOR]

Intracellular Methicillin-Resistant Staphylococcus aureus (MRSA) remains a major factor of refractory and recurrent infections, which cannot be well addressed by antibiotic therapy. Here, we design a cellular infectious microenvironment-activatable polymeric nano-system to mediate targeted intracellular drug delivery for macrophage reprogramming and intracellular MRSA eradication. The polymeric nano-system is composed of a ferrocene-decorated polymeric nanovesicle formulated from poly(ferrocenemethyl methacrylate)- block -poly(2-methacryloyloxyethyl phosphorylcholine) (PFMMA- b -PMPC) copolymer with co-encapsulation of clofazimine (CFZ) and interferon-γ (IFN-γ). The cellular-targeting PMPC motifs render specific internalization by macrophages and allow efficient intracellular accumulation. Following the internalization, the ferrocene-derived polymer backbone sequentially undergoes hydrophobic-to-hydrophilic transition, charge reversal and Fe release in response to intracellular hydrogen peroxide over-produced upon infection, eventually triggering endosomal escape and on-site cytosolic drug delivery. The released IFN-γ reverses the immunosuppressive status of infected macrophages by reprogramming anti-inflammatory M2 to pro-inflammatory M1 phenotype. Meanwhile, intracellular Fe2+-mediated Fenton reaction together with antibiotic CFZ contributes to increased intracellular hydroxyl radical (•OH) generation. Ultimately, the nano-system achieves robust potency in ablating intracellular MRSA and antibiotic-tolerant persisters by synchronous immune modulation and efficient •OH killing, providing an innovative train of thought for intracellular MRSA control. A cellular infectious environment-activatable polymeric nano-system was demonstrated to mediate targeted intracellular drug delivery for macrophage reprogramming and intracellular MRSA eradication. [Display omitted] • A link between M2 macrophage and persistent intracellular infection. • Construction of a cellular infectious microenvironment-activatable polymeric nano-system. • Specific drug delivery for macrophage reprogramming and intracellular •OH generation. • Eradication of intracellular MRSA and antibiotic-tolerant persistersby synchronous immune invoking and •OH killing. [ABSTRACT FROM AUTHOR]

Several stress‐activated signals are highly responsible for the thermal tolerance and attribute to the poor therapeutic outcome of photothermal therapy (PTT). In this study, the naturally human hair‐derived nanoparticles (Hair NPs) with significant photothermal conversion efficacy are explored to combine with stress‐activated signal inhibitors for maximizing the PTT efficiency. During the Hair NPs‐based PTT, two distinct signals are found to be remarkably upregulated. One is the heat‐induced overexpression of HSP90, and the other one is the activation of mitogen‐activated protein kinase (MAPK) signaling pathway. Through the integration of particular inhibitors (17‐allylamino‐17‐demethoxygeldanamycin (17AAG) specifically binding to HSP90 or LY2228820 targeting to p38 MAPK) and the subsequent modification of hyaluronic acid (HA), the resultant Hair NPs‐HA@inhibitor can specifically deliver the inhibitor into tumor cells with minimal side effects on normal tissues, which can specifically block the stressfully activated signals as well as inhibit the expression of their downstream effectors (e.g., MMPs, VEGF) that are closely related with tumor survival and invasion. Without these elements to protect tumor cells or promote tumor progression, the Hair NPs‐induced PTT effect can be much elevated, resulting in a superior antitumor efficacy. These findings represent an effective approach in maximizing PTT effect for fighting against tumor. [ABSTRACT FROM AUTHOR]

Owing to the significant importance in clinics, antibacterial activity is thought as one indispensable feature of the next generation of absorbable sutures. It is challenging but imperative to arm the existing absorbable sutures with antibacterial functions. The present study describes a "gradient deposition" technique to coat a continuous and smooth layer of chitosan on the surface of absorbable sutures. Specifically, chitosan solution is arranged to undergo gradient pH decline step by step while during each pH interval, the solution is allowed to stand for a predetermined period of time in order to control gradual chitosan deposition. Chitosan nanoparticles are found to be first generated on suture surface and finally developed into a smooth chitosan layer as the antibacterial surface. In vitro and in vivo results demonstrated that coating chitosan on sutures by our technique could relieve wound inflammation, stimulate collagen deposition, regenerate blood vessels, and assist tissue repairing, consequently leading to a significant enhancement of wound healing effect. This technique is highlighted with low cost, extreme convenience and excellent safety without organic solvents. Furthermore, the "gradient deposition" technique would not affect the fundamental properties of matrix and thus hold promises as a universal way for superficial antibacterial modification towards almost all the surgical implanted materials, including but not limited to absorbable sutures. [ABSTRACT FROM AUTHOR]

A seed-like hydrogel with metabolic cascade microbiota was demonstrated to achieve efficient oxygen consumption and cascaded hypoxia-induced ammonia elimination, which can reduce hepatotoxic endotoxin and neurotoxic ammonia in situ in the non-invasive treatment of liver failure. [Display omitted] Liver failure is a fatal disease with a mortality rate of 80%. The only access to treat liver failure is invasive operation, which is restricted by limited donor sources or high costs. Thus, non-invasive medication for liver failure is urgently needed. Herein, we tried the first attempt to design a seed-inspired hydrogel with a micro-ecosystem, which imitates characteristics of seed with high intestinal adaptability, for the elimination of harmful metabolites in liver failure using a cascade reaction triggered by encapsulated microbes. Focusing on abnormal ammonia assimilation and intestinal oxygen metabolism, a two-component artificial microbiota was constructed to enable efficient intestinal oxygen consumption and subsequent hypoxia-induced ammonia elimination. More importantly, we imitated plant seeds with high adaptability to the intestinal environment to improve the performance of bacteria. A hydrogel particle with the seed shape, lignin coating, and porous structure, for achieving intentional retention, bacterial protection, and diffusion promotion, respectively was prepared. In murine and porcine models of liver failure, the artificial reactor lowered the blood ammonia to prevent nerve damage, and consumed oxygen to inhibit pathogenic facultative anaerobes for alleviating liver failure. This work underscores the great potential of medication with a bioinspired micro-ecosystem for liver failure. [ABSTRACT FROM AUTHOR]

Cholestatic drug‐induced liver injury (DILI) induced by drugs or other xenobiotics is a severe and even fatal clinical syndrome. Here, living materials of hierarchy‐assembled dual probiotics system are fabricated by sequentially encapsulating probiotic Lactobacillus delbrueckii subsp. bulgaricus (LDB) and Lactobacillus rhamnosus GG (LGG) into Ca2+‐complexed polymer microspheres for effective prevention of cholestatic DILI. Upon entering intestinal tract of the constructed living materials, LGG is released because of pH‐triggered dissolution of outer enteric polymer coating. The released LGG can inhibit hepatic bile acids (BAs) synthesis by activating intestinal farnesoid X receptor‐fibroblast growth factor 15（FGF‐15) signaling pathway. BAs excretion is also facilitated by LGG through increasing the abundance of bile salt hydrolase (BSH)‐active gut commensal bacteria. Furthermore, exposed positively‐charged chitosan shell can absorb the excessive BAs via electrostatic interaction, which leads to steady BAs fixation by the imprisoned LDB, decreasing the total BAs amounts in enterohepatic circulation. Together, the fabricated living materials, obtained here, can effectively prevent cholestatic DILI through dredging cholestasis via gut‐liver axis modulation. The therapeutic effect is demonstrated in α‐naphthylisothiocyanate and clinical antiepileptic drug valproate acid‐induced cholestatic DILI mouse models, which reveal the great potential for effective cholestatic DILI management. [ABSTRACT FROM AUTHOR]

A countermeasure based on ZnO assistant Bdellovibrio (ZnO@Bdello) was reported to remove biofilm in periodontitis. ZnO@Bdello can remove Gram-negative bacteria biofilm, thereby alleviating inflammation, inhibiting bone resorption, and exhibiting an excellent effect in the treatment of periodontitis. [Display omitted] Periodontitis is caused by subgingival plaque biofilm mainly composed of Gram-negative bacteria, affecting human populations at a high prevalence. Antibiotics therapy is the traditional method for periodontitis, but its efficiency in removing plaque biofilm is limited. With the aim to find an effective therapeutic method to treat periodontitis, we reported a material-assistant micro-organism (MAMO) strategy to eradicate Gram-negative bacteria biofilm using ZnO nanorods engineered Bdellovibrio (ZnO@Bdello). Bdellovibrio bacteriovorus is a natural Gram-negative bacteria predator with strong motility. ZnO nanorods are a kind of common piezoelectric material that senses mechanical pressure and produces reactive oxygen species (ROS). During the predation process of Bdellovibrio , the collision of Bdellovibrio triggered ZnO nanorods to produce ROS to enhance the removal of plaque biofilm. Both in vitro and in vivo studies showed ZnO@Bdello could remove biofilm effectively. In addition, ZnO@Bdello possessed superior competence in alleviating inflammation and inhibiting bone resorption in rats and rabbit periodontitis models. Importantly, this strategy does not induce detectable pathogen resistance and side effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ex situ and in situ peptide self-assembly for biomedical applications have been well documented. • Ex situ peptide self-assembly has been carried out to construct cargo delivery carriers, self-deliverable nanomedicines, and tissue engineering materials. • The design principle and trigger module of in situ peptide self-assembly are summarized, with an emphasis on its bioeffects used for disease imaging and therapy. • Peptide re-assembly with morphological adaption is introduced to combat cancers, bacterial infection, and other diseases. In the last few decades, we have witnessed the great advances of molecular self-assembly in biomedical applications. Among the building blocks for molecular self-assembly, peptide exhibits several merits such as structural designability, feasible synthetic methodology, and robust self-assembling tendency. Particularly, the excellent biocompatibility, biodegradability and bioactivity bestow peptide-based assemblies with dominant advantages as biological materials. Herein, the state-of-the-art research on peptide self-assembly is reviewed. First, we discuss the representative achievements of ex situ peptide self-assembly for cargo delivery carriers, self-deliverable nanomedicines, and tissue engineering materials, which are contributed to the prefabrication of micro/nanoarchitectures in solution. After that, the in vitro/in vivo formation of peptide-based nanomaterials is presented, which is nominated as in situ peptide self-assembly. The design principle and trigger module of in situ peptide self-assembly are summarized, with an emphasis on its biological effects used for disease imaging and therapy. Finally, the combinational modality, i.e. integrating ex situ construction of peptide self-assemblies for their delivery with in situ adaptive transformation of their morphologies to optimize outcomes, is attached, which bridges the gap between ex situ and in situ peptide self-assembly. We hope this review will provide a panoramic sketch of peptide self-assembly, which is helpful for chemists and material scientists to exploit more biomedical functions from peptide libraries for disease treatments. [ABSTRACT FROM AUTHOR]

The present study described the case of a 22-year-old woman who had symptoms of left chest pain for >6 months, with further aggravation over 2 days. Computed tomography (CT) images of the mediastinal and pulmonary windows showed low-density shadows in the left ventricle. Echocardiography indicated a slightly stronger echo cluster in the left ventricle, with a range of ~29x30x35 mm, which was closely related to the lower wall and part of the posterior wall of the left ventricle. Contrast-enhanced ultrasound showed that the left ventricular mass was enhanced in a circular and dot-line shape, with a solid mass occupying the left ventricle and a rich blood supply. CT angiography revealed a nodule of size 27x27x24 mm in the left ventricle. During the operation, it was observed that the cardiac lipoma invaded the chordae tendinae and papillary muscle, and a valve replacement was performed. Postoperative examination revealed a piece of gray and anaplastic tissue, measuring 30x22x17 mm. The pathology of the specimen showed that the morphology of the left ventricular mass met the criteria of an intramuscular lipoma. The present study reported a cardiac lipoma involving the left anterior chordae tendinae and papillary muscle, with the patient showing only nonspecific symptoms. Early surgery should be applied to improve the prognosis of cardiac lipoma. [ABSTRACT FROM AUTHOR]

Taking inspiration from percutaneous ethanol injection (PEI) for tumor ablation, an acetaldehyde generator (SC@ZIF@ADH) is constructed for tumor treatment by modifying a metal–organic framework nanocarrier (ZIF), which is loaded with alcohol dehydrogenase (ADH), onto the surface of Saccharomyces cerevisiae (SC). Oral administration of SC@ZIF@ADH can target tumor via mannose‐mediated targeting to tumor associated macrophages (TAMs) and generate ethanol at the hypoxic tumor areas. Ethanol is subsequently catalyzed to toxic acetaldehyde by ADH, inducing tumor cells apoptosis and polarizing TAMs toward the anti‐tumor phenotype. In vivo animal results show that this acetaldehyde generator can cause a temulence‐like reaction in the tumor, significantly inhibiting tumor progression, and might provide an intelligent and nonsurgical substitute for PEI therapy. [ABSTRACT FROM AUTHOR]

Microorganisms have been extensively applied as active biotherapeutic agents or drug delivery vehicles for antitumor treatment because of their unparalleled bio-functionalities. Taking advantage of the living attributes of microorganisms, a new avenue has been opened in anticancer research. The integration of customized functional materials with living microorganisms has demonstrated unprecedented potential in solving existing questions and even conferring microorganisms with updated antitumor abilities and has also provided an innovative train of thought for enhancing the efficacy of microorganism-based tumor therapy. In this review, we have summarized the emerging development of customized materials-assisted microorganisms (MAMO) (including bacteria, viruses, fungi, microalgae, as well as their components) in tumor therapeutics with an emphasis on the rational utilization of chosen microorganisms and tailored materials, the ingenious design of biohybrid systems, and the efficacious antitumor mechanisms. The future perspectives and challenges in this field are also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Driven by the urgent need in practical applications of stimuli-responsive nano-carriers for intracellular drug delivery, the design and development of advanced polymeric micelles capable of responding to the intracellular environment (e.g., ions, proteins, enzymes, and pH changes) has represented a promising strategy as well as a new task in this research field during the past decade. To this end, an effective approach has been to incorporate cleavable links into the polymer structure, either to cause a structural change of the delivery systems, or to direct conjugate drug molecules which could be released on the cleavage of the links. The current review highlights the recent advance in this field and focuses on two types of polymeric micelles that can respond to the physiological signals, i.e., intracellular pH- and reduction-sensitive micelles. [Copyright &y& Elsevier]

Abstract: Aliphatic polycarbonates are one important kind of biodegradable polymers and have been commonly used as integral components of engineered tissues, medical devices and drug delivery systems. As far as the biomedical application is concerned, traditional aliphatic polycarbonates usually suffer from the strong hydrophobicity, deficient functionality, and insufficient compatibility with cell/organs. Consequently, the application is quite limited in scope. Due to the imparted appealing properties, aliphatic polycarbonates bearing specifically designed functional/reactive groups attract great interest from researchers in the recent years. The present review outlines the development up to date concerning the design and biomedical application of functional aliphatic polycarbonates, with an emphasis on their ring-opening (co)polymerization preparation. [Copyright &y& Elsevier]

Amphiphilic copolymers are well developed as precursors for the preparation of micellar drug carriers. Poly(N-isopropylacrylamide) (PNIPAAm) is one of the most extensively studied thermo-sensitive polymers that exhibits a lower critical solution temperature (LCST) at around 33°C in aqueous solution. Over the past decade, considerable efforts have been devoted to design and preparation of PNIPAAm-based thermo-sensitive polymeric micelles as delivery vehicles for controlled drug release. Present review highlights the recent developments in this field, and focuses on two categories of PNIPAAm-based copolymer micelles as smart drug delivery systems, i.e. micelles with PNIPAAm as hydrophilic shell-forming segments below the LCST and micelles with PNIPAAm as hydrophobic core-forming segments above the LCST. [Copyright &y& Elsevier]