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Conventional photocages only respond to short wavelength light, which is a significant obstacle to developing efficient phototherapy in vivo. The development of photocages activated by near‐infrared (NIR) light at wavelengths from 700 to 950 nm is important for in vivo studies but remains challenging. Herein, we describe the synthesis of a photocage based on a ruthenium (Ru) complex with NIR light‐triggered photocleavage reaction. The commercial anticancer drug, tetrahydrocurcumin (THC), was coordinated to the RuII center to create the Ru‐based photocage that is readily responsive to NIR light at 760 nm. The photocage inherited the anticancer properties of THC. As a proof‐of‐concept, we further engineered a self‐assembled photocage‐based nanoparticle system with amphiphilic block copolymers. Upon exposure to NIR light at 760 nm, the Ru complex‐based photocages were released from the polymeric nanoparticles and efficiently inhibited tumor proliferation in vivo. [ABSTRACT FROM AUTHOR]

Radiotherapy is essential for treating unresectable or metastatic breast cancer, but radiotherapy‐induced tumor cell death generates small extracellular vesicles (sEVs) that promote tumor regrowth and metastasis following treatment. Here cationic nanosheets with a high sEVs‐binding capacity that suppress sEVs‐induced tumor regrowth and metastasis following radiotherapy is developed. Molybdenum disulfide (MoS2) monolayers are prepared by using lithium ions as intercalation agents, and are functionalized with cationic polyamidoamine (PAMAM) dendrimers. The MoS2‐PAMAM particles exhibit a corrugated sheet‐like nanostructure with a larger surface‐to‐volume ratio than spherical PAMAM‐functionalized particles, resulting in greater sEVs binding capacity. Treatment of MDA‐MB‐231 human breast cancer cells with the MoS2‐PAMAM nanosheets reduces sEVs‐induced Toll‐like receptor activation and tumor cell proliferation, migration, and invasion to a greater extent than treatment with spherical PAMAM nanoparticles. In a mouse 4T1 metastatic breast cancer model, the nanosheets exhibit greater inhibition of tumor regrowth and metastasis after radiotherapy than the spherical nanoparticles, demonstrating the potential of these sEVs‐scavenging nanosheets for improving outcomes for breast cancer radiotherapy patients. The work reveals a pivotal role of the 2D sheet‐like materials in binding sEVs, indicating the significance of nanoscale geometry in developing the next‐generation sEVs‐scavenging biomaterials. [ABSTRACT FROM AUTHOR]

Bacterial infection and excessive inflammation following abdominal injury can cause life‐threatening complications that lead to multiple organ failure and death. Removing bacteria and proinflammatory factors—which are predominantly negatively charged—from the wound site with a cationic, antibiotic‐containing hydrogel wound dressing is therefore a promising treatment approach for severe abdominal trauma. Here an injectable, self‐healing hydrogel composed of the gel‐forming glycosaminoglycan oxidized chondroitin sulfate (OCS), cationic polyethylenimine (PEI), and the antibiotic tobramycin (Tob) via a Schiff's base reaction is developed. Compared with hydrogels lacking either PEI or Tob, only the Tob/PEI/OCS hydrogels exhibit a large binding capacity for negatively‐charged proinflammatory factors including cell‐free DNA, lipopolysaccharides, TNF‐α, and high mobility group box 1 protein, and a large reduction in bacterial populations in vitro. In a murine model of severe abdominal trauma, the Tob/PEI/OCS hydrogel exhibits good biodegradability and biosafety, reduced local and systemic inflammation and infection, and prevents multiple organ failure, resulting in 100% survival. This hydrogel dressing is thus a promising biomaterial for preventing complications and improving outcomes following severe abdominal trauma. [ABSTRACT FROM AUTHOR]

The integration of silver nanoparticles (Ag NPs) with mesoporous silica nanoparticles (MSNs) protects the former from aggregation and promotes the controlled release of silver ions, resulting in therapeutic significance on cancer and infection. The unique size, shape, pore structure and silver distribution of silver mesoporous silica nanoparticles (Ag‐MSNs) embellish them with the potential to perform combined imaging and therapeutic actions via modulating optical and drug release properties. Here, we comprehensively review the recent progress in the fabrication and application of Ag‐MSNs for combination therapies for cancer and infection. We first elaborate on the fabrication of star‐shaped structure, core‐shell structure, and Janus structure Ag‐MSNs. We then highlight Ag‐MSNs as a multifunctional nanoplatform to surface‐enhanced Raman scattering‐based detection, non‐photo‐based cancer theranostics and photo‐based cancer theranostics. In addition, we detail Ag‐MSNs for combined antibacterial therapy via drug delivery and phototherapy. Overall, we summarize the challenges and future perspectives of Ag‐MSNs that make them promising for diagnosis and therapy of cancer and infection. [ABSTRACT FROM AUTHOR]

Biomimetic strategies are useful for designing potent vaccines. Decorating a nanoparticulate adjuvant with cell membrane fragments as the antigen‐presenting source exemplifies, such as a promising strategy. For translation, a standardizable, consistent, and scalable approach for coating nanoadjuvant with the cell membrane is important. Here a turbulent mixing and self‐assembly method called flash nanocomplexation (FNC) for producing cell membrane‐coated nanovaccines in a scalable manner is demonstrated. The broad applicability of this FNC technique compared with bulk‐sonication by using ten different core materials and multiple cell membrane types is shown. FNC‐produced biomimetic nanoparticles have promising colloidal stability and narrow particle polydispersity, indicating an equal or more homogeneous coating compared to the bulk‐sonication method. The potency of a nanovaccine comprised of B16‐F10 cancer cell membrane decorating mesoporous silica nanoparticles loaded with the adjuvant CpG is then demonstrated. The FNC‐fabricated nanovaccines when combined with anti‐CTLA‐4 show potency in lymph node targeting, DC antigen presentation, and T cell immune activation, leading to prophylactic and therapeutic efficacy in a melanoma mouse model. This study advances the design of a biomimetic nanovaccine enabled by a robust and versatile nanomanufacturing technique. [ABSTRACT FROM AUTHOR]

Although adoptive transfer of therapeutic cells to cancer patients is demonstrated with great success and fortunately approved for the treatment of leukemia and B‐cell lymphoma, potential issues, including the unclear mechanism, complicated procedures, unfavorable therapeutic efficacy for solid tumors, and side effects, still hinder its extensive applications. The explosion of nanotechnology recently has led to advanced development of novel strategies to address these challenges, facilitating the design of nano‐therapeutics to improve adoptive cell therapy (ACT) for cancer treatment. In this review, the emerging nano‐enabled approaches, that design multiscale artificial antigen‐presenting cells for cell proliferation and stimulation in vitro, promote the transducing efficiency of tumor‐targeting domains, engineer therapeutic cells for in vivo imaging, tumor infiltration, and in vivo functional sustainability, as well as generate tumoricidal T cells in vivo, are summarized. Meanwhile, the current challenges and future perspectives of the nanostrategy‐based ACT for cancer treatment are also discussed in the end. [ABSTRACT FROM AUTHOR]

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and painful bladder condition afflicting patients with increased urinary urgency and frequency as well as incontinence. Owing to the elusive pathogenesis of IC/BPS, obtaining effective therapeutic outcomes remains challenging. Current administrational routes such as intravesical-bladder injection improve the treatment efficacy and reduce systemic side effects. However, the bladder permeability barrier hinders drug penetration into the bladder wall to meet the desired therapeutic expectation. These issues can be addressed by encapsulating drugs into biomaterials. When appropriately exploited, they would increase the drug dwelling time in the bladder, enhance the penetration of mucosa and improve the therapeutic response of IC/BPS. In this review, we first elucidate the pathogenesis and animal models of IC/BPS. Then, we highlight recent representative biomaterial-assisted drug delivery systems for IC/BPS treatment. Finally, we discuss the challenges and outlook for further developing biomaterial-based delivery systems for IC/BPS management. [ABSTRACT FROM AUTHOR]

The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology enables genome editing with high precision and versatility and has been widely utilized to combat viruses, bacteria, cancers, and genetic diseases. Nonviral nanocarriers can overcome several limitations of viral vehicles, including immunogenicity, inflammation, carcinogenicity, and low versatility, and thus represent promising platforms for CRISPR/Cas9 delivery. Herein, we for the first time develop the application of protamine-capped gold nanoclusters (protamine–AuNCs) as an effective nanocarrier for Cas9–sgRNA plasmid transport and release to achieve efficient genome editing. The protamine–AuNCs integrate the merits of AuNCs and protamine: AuNCs are able to promptly assemble with Cas9–sgRNA plasmids to allow efficient cellular delivery, while the cationic protamine facilitates the effective release of Cas9–sgRNA plasmids into the cellular nucleus. The AuNCs/Cas9–gRNA plasmid nanocomplexes can not only achieve successful gene editing in cells but also knock out the oncogenic gene for cancer therapy. Moreover, the AuNCs with excellent photoluminescence characteristics endow our nanoplatform with the functionality of bioimaging. Overall, our study provides strong evidence that demonstrates protamine–AuNCs as an effective CRISPR/Cas9 delivery tool for gene therapy. [ABSTRACT FROM AUTHOR]

Photocages, Ruthenium complex, NIR light, Polymer nanoparticles, Photocleavage reaction Keywords: Photocages; Ruthenium complex; NIR light; Polymer nanoparticles; Photocleavage reaction EN Photocages Ruthenium complex NIR light Polymer nanoparticles Photocleavage reaction 1 1 1 06/06/23 20230612 NES 230612 B A ruthenium-based photocage b that can be activated by 760 nm NIR light via single-photon pathway is reported by Xuezhao Li, Wen Sun et al. in their Research Article (e202218768). The photocage was engineered into amphiphilic block copolymers, forming nanoparticles via self-assembly, which release the ruthenium complex-based photocages to inhibit tumor proliferation in vivo upon exposure to NIR light. [Extracted from the article]

Inside Back Cover: A Near-Infrared Light-Activated Photocage Based on a Ruthenium Complex for Cancer Phototherapy (Angew. The photocage was engineered into amphiphilic block copolymers, forming nanoparticles via self-assembly, which release the ruthenium complex-based photocages to inhibit tumor proliferation in vivo upon exposure to NIR light. Photocages, Ruthenium complex, NIR light, Polymer nanoparticles, Photocleavage reaction. [Extracted from the article]

Photodynamic therapy (PDT) is clinically promising in destructing primary tumors but ineffective against distant metastases. This study reports the use of immunogenic nanoparticles mediated combination of PDT and magnetic hyperthermia to synergistically augment the anti‐metastatic efficacy of immunotherapy. Janus nanobullets integrating chlorine e6 (Ce6) loaded, disulfide‐bridged mesoporous organosilica bodies with magnetic heads (M‐MONs@Ce6) are tailored for redox/pH‐triggered photosensitizer release accompanying their matrix degradation. Cancer cell membrane cloaking enables favorable tumor‐targeted accumulation and prolonged blood circulation time of M‐MONs@Ce6. The combination of PDT and magnetic hyperthermia has a strong synergy anticancer activity and simultaneously elicits a sequence of immunogenic cell death, resulting in synergistically tumor‐specific immune responses. When combined with anti‐CTLA‐4 antibody, the biomimetic and biodegradable nanoparticle enables the notable eradication of primary and deeply metastatic tumors with low systematic toxicity, thus potentially advancing the development of combined hyperthermia, PDT, and checkpoint blockade immunotherapy to combat cancer metastasis. [ABSTRACT FROM AUTHOR]

Inflammation is ubiquitous in the body, triggering desirable immune response to defend against dangerous signals or instigating undesirable damage to cells and tissues to cause disease. Nanomedicine holds exciting potential in modulating inflammation. In particular, cell membranes derived from cells involved in the inflammatory process may be used to coat nanotherapeutics for effective targeted delivery to inflammatory tissues. Herein, the recent progress of rationally engineering cell membrane‐based nanotherapeutics for inflammation therapy is highlighted, and the challenges and opportunities presented in realizing the full potential of cell‐membrane coating in targeting and manipulating the inflammatory microenvironment are discussed. [ABSTRACT FROM AUTHOR]

A therapeutic strategy that targets multiple proinflammatory factors in inflammatory bowel disease (IBD) with minimal systemic side effects would be attractive. Here, we develop a drug-free, biodegradable nanomedicine that acts against IBD by scavenging proinflammatory cell-free DNA (cfDNA) and reactive oxygen species (ROS). Polyethylenimine (PEI) was conjugated to antioxidative diselenide-bridged mesoporous organosilica nanoparticles (MONs) to formulate nanoparticles (MON-PEI) that exhibited high cfDNA binding affinity and ROS-responsive degradation. In ulcerative colitis and Crohn's disease mouse colitis models, orally administered MON-PEI accumulated preferentially in the inflamed colon and attenuated colonic and peritoneal inflammation by alleviating cfDNA- and ROS-mediated inflammatory responses, allowing a reduced dose frequency and ameliorating colitis even after delayed treatment. This work suggests a new nanomedicine strategy for IBD treatment.

Highlights: This review focuses on the therapeutic mechanisms, targeting strategies of various nanomaterials in acute liver failure, and recent advances of diverse nanomaterials for acute liver failure therapy, diagnosis, and imaging. This review provides an outlook on the applications of nanomaterials, especially on the new horizons in acute liver failure therapy, and inspires broader interests across various disciplines. Acute liver failure (ALF), a fatal clinical disease featured with overwhelming hepatocyte necrosis, is a grand challenge in global health. However, a satisfactory therapeutic option for curing ALF is still absent, other than liver transplantation. Nanobiomaterials are currently being developed for the diagnosis and treatment of ALF. The liver can sequester most of nanoparticles from blood circulation, which becomes an intrinsic superiority for nanobiomaterials targeting hepatic diseases. Nanobiomaterials can enhance the bioavailability of free drugs, thereby significantly improving the therapeutic effects in ALF. Nanobiomaterials can also increase the liver accumulation of therapeutic agents and enable more effective targeting of the liver or specific liver cells. In addition, stimuli-responsive, optical, or magnetic nanomaterials exhibit great potential in the therapeutical, diagnostic, and imaging applications in ALF. Therefore, therapeutic agents in combination with nanobiomaterials increase the specificity of ALF therapy, diminish adverse systemic effects, and offer a multifunctional theranostic platform. Nanobiomaterial holds excellent significance and prospects in ALF theranostics. In this review, we summarize the therapeutic mechanisms and targeting strategies of various nanobiomaterials in ALF. We highlight recent developments of diverse nanomedicines for ALF therapy, diagnosis, and imaging. Furthermore, the challenges and future perspectives in the theranostics of ALF are also discussed.

Severe sepsis represents a common, expensive, and deadly health care issue with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis would help develop new therapeutic strategies against severe sepsis. In this study, we identified the crucial role of cell-free DNA (cfDNA) in the regulation of the Toll-like receptor 9-mediated proinflammatory pathway in severe sepsis progression. Hypothesizing that removing cfDNA would be beneficial for sepsis treatment, we used polyethylenimine (PEI) and synthesized PEI-functionalized, biodegradable mesoporous silica nanoparticles with different charge densities as cfDNA scavengers. These nucleic acid-binding nanoparticles (NABNs) showed superior performance compared with their nucleic acid-binding polymer counterparts on inhibition of cfDNA-induced inflammation and subsequent multiple organ injury caused by severe sepsis. Furthermore, NABNs exhibited enhanced accumulation and retention in the inflamed cecum, along with a more desirable in vivo safety profile. Together, our results revealed a key contribution of cfDNA in severe sepsis and shed a light on the development of NABN-based therapeutics for sepsis therapy, which currently remains intractable., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Mesenchymal stem cell (MSC) has been increasingly applied to cancer therapy because of its tumor-tropic capability. However, short retention at target tissue and limited payload option hinder the progress of MSC-based cancer therapy. Herein, we proposed a hybrid spheroid/nanomedicine system, comprising MSC spheroid entrapping drug-loaded nanocomposite, to address these limitations. Spheroid formulation enhanced MSC's tumor tropism and facilitated loading of different types of therapeutic payloads. This system acted as an active drug delivery platform seeking and specifically targeting glioblastoma cells. It enabled effective delivery of combinational protein and chemotherapeutic drugs by engineered MSC and nanocomposite, respectively. In an in vivo migration model, the hybrid spheroid showed higher nanocomposite retention in the tumor tissue compared with the single MSC approach, leading to enhanced tumor inhibition in a heterotopic glioblastoma murine model. Taken together, this system integrates the merits of cell- and nanoparticle- mediated drug delivery with the tumor-homing characteristics of MSC to advance targeted combinational cancer therapy.

Peripheral nerve blockade (PNB) is a conventional strategy for the management of acute postoperative pain. However, the short duration of the associated analgesia and the potential systemic toxicity due to the low molecular weights of local anesthetics limit their application. Methods: An in situ forming injectable Gel-microsphere (Gel-MS) system consisting of PLGA-PEG-PLGA Gel (Gel) and Gel-immobilized bupivacaine-loaded microsphere (MS/BUP) was prepared for precision-guided long-acting analgesia. A series of in vitro characterizations, such as scanning electron microscopy, rheology analysis, confocal laser scanning microscopy, drug release, and erosion and degradation, were carried out. After that, the in vivo analgesia effect of the Gel-MS system, the immobilization effect of Gel on the MS, and biocompatibility of the system were evaluated using a sciatic nerve block model. Results: The BUP release from the Gel-MS system was regulated by both the inner MS and the outer Gel matrix, demonstrating sustained BUP release in vitro for several days without an initial burst release. More importantly, incorporation of the Gel immobilized the MS and hindered the diffusion of MS from the injection site because of its in situ property, which contributed to a high local drug concentration and prevented systemic side effects. In vivo , a single injection of Gel-MS/BUP allowed rats to maintain sensory and motor blockade significantly longer than treatment with MS/BUP ( P < 0.01) or BUP-loaded Gel (Gel-BUP, P < 0.01). Histopathological results demonstrated the excellent biodegradability and biocompatibility of the Gel-MS system without neurotoxicity. Conclusion: This precision-guided long-acting analgesia, which provides an in situ and sustained release of BUP, is a promising strategy for long-acting analgesia, and could represent a potential alternative for clinical pain management., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Magnetic mesoporous silica nanoparticles (M-MSNs) are attractive candidates for the immunomagnetic isolation and detection of circulating tumor cells (CTCs). Understanding of the interactions between the effects of the shape of M-MSNs and CTCs is crucial to maximize the binding capacity and capture efficiency as well as to facilitate the sensitivity and efficiency of detection. In this work, fluorescent M-MSNs were rationally designed with sphere and rod morphologies while retaining their robust fluorescence and uniform surface functionality. After conjugation with the antibody of epithelial cell adhesion molecule (EpCAM), both of the differently shaped M-MSNs-EpCAM obtained achieved efficient enrichment of CTCs and fluorescent-based detection. Importantly, rodlike M-MSNs exhibited faster immunomagnetic isolation as well as better performance in the isolation and detection of CTCs in spiked cells and real clinical blood samples than those of their spherelike counterparts. Our results showed that shape engineering contributes positively toward immunomagnetic isolation, which might open new avenues to the rational design of magnetic-fluorescent nanoprobes for the sensitive and efficient isolation and detection of CTCs.