A pH and glutathione-responsive carbon monoxide-driven nano-herb delivery system for enhanced immunotherapy in colorectal cancer

Journal of Controlled Release, Год журнала: 2024, Номер 376, С. 659 - 677

Опубликована: Окт. 28, 2024

Язык: Английский

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Advances in Engineered Phages for Disease Treatment

Small Methods, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Abstract Phage therapy presents a promising solution for combating multidrug‐resistant (MDR) bacterial infections and other bacteria‐related diseases, attributed to their innate ability target lyse bacteria. Recent clinical successes, particularly in treating MDR‐related respiratory post‐surgical infections, validated the therapeutic potential of phage therapy. However, complex microenvironment within human body poses significant challenges activity efficacy vivo. To overcome these barriers, recent advances engineering have aimed enhance targeting accuracy, improve stability survivability, explore synergistic combinations with modalities. This review provides comprehensive overview therapy, emphasizing application engineered phages antibacterial tumor vaccine development. Furthermore, highlights current future trends advancing toward broader applications.

Язык: Английский

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A Peptide‐Derived Aggregation‐Induced Emission Nanobioprobe: Unlocking Selective Detection of Fusobacterium nucleatum and Noninvasive Screening of Colorectal Cancer

Aggregate, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

ABSTRACT Colorectal cancer (CRC) screening and early diagnosis is an effective strategy for reducing CRC mortality. However, the current detection methods involve exorbitant costs complex procedures, which are inconvenient large‐scale screening. Given its high prevalence in malignant tissues feces of patients, Fusobacterium nucleatum ( F. ) has emerged as a crucial biomarker CRC. Herein, we propose ‐specific recognition diagnosis. A novel nanobioprobe (AIE‐Pep) with aggregation‐induced emission (AIE) characteristics was synthesized by conjugating red/near‐infrared (NIR) emissive AIE luminogen (AIEgen) FadA‐targeting peptide (ASANWTIQYND). The robust binding affinity between FadA on allows AIE‐Pep NPs to adhere selectively , emits strong red/NIR fluorescence. In model orthotopic CRC, can precisely localize around Moreover, demonstrated limit (LOD) 82.97 CFU/mL could significantly differentiate mice from those normal mice. Overall, this study presents pivotal approach specifically identifying holds immense potential

Язык: Английский

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The challenge and opportunity of gut microbiota‐targeted nanomedicine for colorectal cancer therapy

iMeta, Год журнала: 2024, Номер 3(4)

Опубликована: Июнь 10, 2024

The gut microbiota is an integral component of the colorectal cancer (CRC) microenvironment and intimately associated with CRC initiation, progression, therapeutic outcomes. We reviewed recent advancements in utilizing nanotechnology for modulating microbiota, discussing strategies mechanisms underlying their design. For future nanomedicine design, we propose a 5I principle individualized management. Colorectal third most prevalent malignancy has become clinically challenging disease along second leading cause cancer-related deaths globally, which usually attributed to its recurrence metastasis [1, 2]. Emerging evidence suggests that especially pathogenic microbes, metabolites, constitute tumor microenvironment, demonstrating intimate association initiation progression While diversity can differ significantly among individuals, large-scale multicohort analysis metagenome revealed consistent enrichment specific microbiomes tumorigenesis functions, indicating correlation during progression. example, dysbiotic expansion intestinal mucosa-associated Enterobacteriaceae, common pathogen, strongly inflammatory bowel (IBD) occurrence [1-3]. Moreover, over-representation could potentially counteract traditional treatment regimens promote [2]. instance, Fusobacterium nucleatum (Fn), pro-tumoral bacterium, rarely found lower gastrointestinal tract healthy individuals but often enriched human tumors [4]. Its presence promotes chemoresistance oxaliplatin 5-fluorouracil (5-FU) correlates poor prognosis patients [2, 4]. Apart from pathogenesis function, some preclinical clinical studies also underscore critical role metabolites improving antitumor responses efficacy chemotherapy, radiotherapy, immunotherapy [2], burgeoning field microbiota-related interventions. Recent have demonstrated microbiome modulation through oral administration commensal bacteria, such as Bacteroidales, Bifidobacterium, Akkermansia muciniphila (AKK), augment efficiency first-line chemotherapy treatments enhance CTLA-4- or PD-L1-mediated immunotherapies Therefore, regulation antibiotics, fecal transplants (FMT), probiotics, prebiotics, diet modifications, promising approach inhibiting carcinogenesis FMT direct intervention by reversing microbial dysbiosis ameliorating inflammation improve immune anticancer Supplementations probiotics and/or prebiotics inhibit development Gut responds changes bacterial-derived short-chain fatty acids (SCFA). SCFA-guided enhances mouse models However, current approaches treating not manipulate intratumoral efficacy. Antibiotic therapy alone lacks tumor- intracellular-targeting, limits effectiveness against tumor-associated bacteria. Meanwhile, complexity anatomical physiology multiple physical barriers impede precise editing conventional regimes. Recently, dramatically transformed landscape past decades [5, 6]. there urgent need develop new pathophysiology-oriented microbiota-targeted therapies precisely remove cancer-causing bacteria colonization beneficial species [7]. advantage nanoscale drug delivery systems lies ability bypass issues related solubility vulnerability harsh chemical biological conditions (such gastric pH enzymes) capacity tumor-targeted accumulation reduce systemic exposure diverse functionality provides engineers facets microbiome, enabling possibility applying employ bacteria-targeting ligands guide drug-loaded carrier tumors. These emerging intelligent nanocarriers provide feasibility on-demand (Table 1). straightforward strategy remodeling involves directly interfering tumor-colonized using nanomedicines. intense interaction between Fn membrane protein Fap-2 overexpressed D-galactose-β-(1-3)-N-acetyl-D-galactosamine (Gal-GalNAc) on cells facilitates reduces checkpoint blockade (ICB) efficacy, evidenced samples animal [8]. Hence, selectively killing without causing vital [9, 10]. Dong colleagues assembled silver nanoparticles (AgNP) Fn-binding M13 phage (M13@Ag) clear remodel tumor-immune [9]. Oral intravenous azide-modified eradicate pathobiont induced potentiate activity folinic acid-5-FU-irinotecan [10]. distinct clade was reported dominate [17]. employing Fna C2 membrane-constructed achieve targeted eradication impacting ecology. Besides Fn, other microorganisms like Enterotoxigenic Bacteroides fragilis (ETBF) been identified worse nanomedicines should be designed eliminate wide selective range protumoral pathogens rather than exclusively targeting individual species. Jiang proposed nanocatalytic tumor-immunotherapeutic method disintegration (TAB) trigger innate immunity situ cooperatively [11]. Unlike this Fenton reaction under alternating magnetic field-induced hyperthermia generating cytotoxic hydroxyl radicals situ. Although achieved bacteriophage bacterial materials, barely any CRC-associate identified. main challenge CRC-associated achieving efficient medicines, equipping newly delivery. Beyond increasing supports existence intracellular broad spectrum cells, disrupting surveillance mediating escape activating suppressive pathways (TME). integrating chemotherapeutics antibiotics represents synergistic eradicating offering strategic management [12, 18]. Gao synthesized amphiphilic small molecule combining metronidazole (MTZ) fluorouridine (5-FU), cleavable response elevated glutathione (GSH) levels, impact released antibiotic chemotherapeutic, both [18]. In same way, Chen developed AB-Gel tumor-triggered release MTZ 5-FU, cell growth perfusion [12]. efficiently suppressed orthotopic model MTZ-induced CRC-related enhanced via elimination. intracellularly offer alternative neoepitopes immunotherapy. Selectively these within may expose epitopes, sources cancer-associated neoantigens. Wang engineered liposomes encapsulating silver-tinidazole complex (LipoAgTNZ) primary liver metastases while preserving homeostasis [13]. Mice colonized either tumor-promoting exhibited positive LipoAgTNZ treatment, long-term survival rate exceeding 70% two infected Fn. Additionally, produced neoantigens, CD8+ T priming them recognize uninfected summary, nano-sized whether intertumor elimination, leverage advantageous features nanoparticles, stability, capacity, improved bioavailability, advance nanomaterials used antibacterial materials dysbiosis-associated diseases, including IBD CRC, discoveries pave way elimination demand. abnormally proliferated mucosal barrier physiological structures [3, 5, essential maintaining host health [3]. Liu presented self-thermophoretic (CTPB) cloaked biomimetic Staphylococcus aureus, aiming localization segment [19]. Upon near-infrared laser irradiation, CTPB showed noteworthy 2.7-fold enhancement mucus penetration simultaneous 3.5-fold reduction interception, CRC-bearing mice, impressive 99.4% rate. eliminating microbiomes, bioengineered colonize enable novel effect prevention treatment. Probiotic strains safety investigated biotherapeutic agents trials. probiotic encounters obstacles specificity, unique penetration, dosage adjustability. Engineering tumor-colonizing Escherichia coli Nissle 1917 explicitly tumor-targeting adhesion heparan sulfate proteoglycan result >95% proliferation inhibition adenoma burden ~50% vivo [16]. Engineered lactic acid bacterium Pediococcus pentosaceus harboring P8 ameliorate impaired regression [20]. administered enrich genera SCFAs cyclic diadenosine monophosphate (cyclic di-AMP), active immunity, respectively. Zheng fabricated prebiotic-encapsulated spores (spores-dex) host–guest interactions commercially available Clostridium butyricum chemically modified dextran. Following administration, spores-dex accumulate colon cancers, where dextran undergoes fermentation butyricum, production [14]. Besides, orally capecitabine-loaded prebiotic xylan-stearic immunotherapeutic 5.29% 71.78% extended time 14 33.5 days facilitating SCFA [15]. As opportunities use nanotechnologies depletion induction challenges arise infiltration, internalized targeting, immunological (5I) will addressed (Figure (1) Individualized nanomedicine: composed tumor-type-specific closely nanotherapeutic interventions applied case personalized medicine. (2) Intestinal infiltration: intravenously infused nanomedicines, heavily rely permeation retention (EPR) effect, administrable typically face low bioavailability due physicochemical (GIT). overcome deliver drugs locations. (3) Internalized probiotics: safe effective future. incidence quality life. (4) Intratumoral targeting: Tumor-associated patient-unique ecosystem dynamically diet, environment, drugs, factors, hence target kill microbiome. (5) Immunological regulation: desensitizes host-mediated results immunoresistance efficacy; previously summarized, major inroads empowered therapy. Eradicating supplementing all fulfill multifaceted demands usher era stimulus-responsive payload release, subsequent Hanqing conceived coordinated work. Rui Guangjun Nie provided direction guidance throughout preparation manuscript. Yaohua Wei, Ruifang Zhao, Huidong Song, Feng Shen authored paper. revised Wei drew diagrams. Weiyue Feng, Yue Pan, Xiaobo Li, Huanling Yu, Giuseppe Familiari, Michela Relucenti, Michael Aschner, Hanping Shi All authors read final manuscript approved it publication. This work supported grants National Basic Research Plan China (2023YFC2508503 2021YFA0909900 Zhao), Science Fund Distinguished Young Scholars (82025031 Chen), Natural Foundation (32171370 CAS Project Scientists (YSBR-041 Beijing Nova Program (202304584382 Guangdong Province (2022A1515010415 Scientific Technological Innovation Academy Chinese Medical Sciences (CI2023C012YL Technology Guangzhou (2023A03J0493 Song). declare no conflict interest. No animals humans were involved study. data generated Supporting Information (graphical abstract, slides, videos, translated version, update materials) online DOI iMeta http://www.imeta.science/.

Язык: Английский

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Engineering lauric acid-based nanodrug delivery systems for restoring chemosensitivity and improving biocompatibility of 5-FU and OxPt against Fn-associated colorectal tumor

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(16), С. 3947 - 3958

Опубликована: Янв. 1, 2024

Colorectal cancer (CRC) occurs in the colorectum and ranks second global incidence of all cancers, accounting for one highest mortalities. Although combination chemotherapy regimen 5-fluorouracil (5-FU) platinum(IV) oxaliplatin prodrug (OxPt) is an effective strategy CRC treatment clinical practice, resistance caused by tumor-resided Fusobacterium nucleatum (Fn) could result failure. To enhance efficacy improve biocompatibility chemotherapy, we developed antibacterial-based nanodrug delivery system Fn-associated treatment. A tumor microenvironment-activated nanomedicine 5-FU-LA@PPL was constructed self-assembly chemotherapeutic drug derivatives 5-FU-LA polymeric carrier PPL. PPL prepared conjugating lauric acid (LA) OxPt to hyperbranched polyglycidyl ether. In principle, LA used selectively combat Fn, inhibit autophagy cells, restore chemosensitivity 5-FU as well OxPt, consequently effects drug-resistant colorectal tumor. Both vitro vivo studies exhibited that tailored possessed efficient antibacterial anti-tumor activities with improved reduced non-specific toxicity. Hence, this novel has great potential CRC, which suggests a clinically relevant valuable option bacteria-associated cancers.

Язык: Английский

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Various Antibacterial Strategies Utilizing Titanium Dioxide Nanotubes Prepared via Electrochemical Anodization Biofabrication Method

Biomimetics, Год журнала: 2024, Номер 9(7), С. 408 - 408

Опубликована: Июль 5, 2024

Currently, titanium and its alloys have emerged as the predominant metallic biomaterials for orthopedic implants. Nonetheless, relatively high post-operative infection rate (2-5%) exacerbates patient discomfort imposes significant economic costs on society. Hence, urgent measures are needed to enhance antibacterial properties of alloy The dioxide nanotube array (TNTA) is gaining increasing attention due topographical photocatalytic properties. Moreover, pores within TNTA serve excellent carriers chemical ion doping drug loading. fabrication surface can be achieved through various methods. Studies demonstrated that electrochemical anodization method offers numerous advantages, such simplicity, cost-effectiveness, controllability. This review presents development process applications in synthesizing TNTA. Additionally, this article systematically discusses topographical, chemical, delivery, combined strategies. It widely acknowledged implants should possess a range favorable biological characteristics. Clearly, addressing multiple needs with single strategy challenging. proposes systematic research into strategies further mitigate risks implant success rates future.

Язык: Английский

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Tumor and intratumoral pathogen cascade-targeting photothermal nanotherapeutics for boosted immunotherapy of colorectal cancer

Journal of Controlled Release, Год журнала: 2025, Номер 379, С. 574 - 591

Опубликована: Янв. 24, 2025

Язык: Английский

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Enhanced precise therapy of ROS-sensitive dual-layer shell nanoparticles loading quercetin on DSS-induced ulcerative colitis mice

APL Materials, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 1, 2025

Ulcerative colitis (UC) is an intestinal condition, involving inflammatory response, apoptosis, and associated processes. As one of the traditional Chinese medicine treatments for UC, quercetin has received attention because it can attenuate inflammation. However, oral administration does not perform well in therapy. In this study, reactive oxygen species (ROS)-sensitive nanoparticles (Que@Gel-DA NPs) prepared by self-assembly polymerization were proposed treatment UC. Quercetin was encapsulated within a shell layer gelatin, followed dopamine on gelatin surface. Relative to free form quercetin, dual-layer encapsulation enhanced solubility bioavailability achieved intragastric protection, extended resident time gastrointestinal tract. Upon reaching colon lesion, underwent degradation response ROS, served enhance biocompatibility mitigate burst release. This resulted controlled release which enabled precise therapy exerted antibacterial anti-inflammatory effects. Furthermore, Que@Gel-DA NPs significantly alleviated UC symptoms dextran sodium sulfate (DSS)-induced mouse model. evidenced significant increase body weight, reduction occult blood feces, recovery crypt structure. The stained results indicated that inflammation promoting polarization M2 macrophages reduce apoptosis modulate immunity. Therefore, NPs, ROS-sensitive nano-drug delivery system, represent novel therapeutic approach clinical intervention

Язык: Английский

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Recent advances in therapeutic probiotics: insights from human trials

Clinical Microbiology Reviews, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

SUMMARY Recent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome’s role and disease. However, comprehensive reviews integrating diverse effects subjects been limited. By analyzing randomized controlled trials (RCTs) meta-analyses, this review provides overview key developments probiotic interventions targeting gut, liver, skin, vaginal, mental, oral health. Emerging evidence supports efficacy specific strains combinations treating wide range disorders, from gastrointestinal (GI) liver diseases to dermatological bacterial vaginosis, mental diseases. We discuss expanding microbiome-organ connections underlying mechanisms action. While many clinical demonstrate significant benefits, we acknowledge areas requiring further large-scale studies establish definitive optimal treatment protocols. The addresses challenges standardizing research methodologies emphasizes importance considering individual variations microbiome composition host genetics. Additionally, explore emerging concepts such as oral-gut-brain axis future directions, including high-resolution profiling, host-microbe interaction studies, organoid models, artificial intelligence applications research. Overall, offers update on current state multiple domains health, providing insights into directions potential for revolutionize preventive medicine.

Язык: Английский

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Neutrophil‐Mimicking Nanomedicine Eliminates Tumor Intracellular Bacteria and Enhances Chemotherapy on Liver Metastasis of Colorectal Cancer

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Май 28, 2025

Abstract Fusobacterium nucleatum ( Fn ) enrichment has been identified in colorectal cancer and its liver metastases. In this study, we found that predominantly accumulated within cells, correlating with metastasis. Clinically, the administration of high doses antibiotics chemotherapeutic agents can disrupt balance host microbiota. To address clinical challenge, metronidazole (MTI) oxaliplatin (OXA) are encapsulated poly (lactic‐co‐glycolic acid) (PLGA) nanoparticles. Neutrophil membrane vesicles extracted from murine bone marrow coated these nanoparticles (NM@PLGA‐MTI‐OXA), creating neutrophil‐mimetic dual targeting capabilities for antibacterial anticancer purposes. The neutrophil coating, compared free drugs, is to enhance nanoparticle uptake by tumor facilitating intracellular bacterial elimination cell death. Further experiments reveal NM@PLGA‐MTI‐OXA reverses ‐induced epithelial‐mesenchymal transition (EMT) cells during metastasis remodels immunosuppressive microenvironment, suppressing development while minimizing broad‐spectrum damage commensal

Язык: Английский

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