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US/PA/MR multimodal imaging-guided multifunctional genetically engineered bio-targeted synergistic agent for tumor therapy. US/PA/MR 多模态成像引导的多功能基因工程生物靶向协同制剂用于肿瘤治疗。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s12951-024-02868-9
Li Ren, Yaotai Wang, Yu Tang, Fang Wang, Yan Du, Xia Ou, Li Lin, Zhong Zhang, Yan Ding, Meixian Wu, Yijun Zhou, Mingyang Zhang, Qi Wang, Jianzhong Zou

Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy.

聚焦超声消融手术(FUAS)是一种微创治疗方法,已被用于多种肿瘤的治疗。然而,其安全性和效率低、图像引导模式单一、术后肿瘤残留等问题阻碍了其临床推广。针对这些局限性,本研究旨在开发一种新型多功能产气工程菌生物靶向协同系统。通过对大肠杆菌(E.coli)进行基因改造,插入声学报告基因来编码气体囊泡(GVs),从而产生了能够靶向肿瘤缺氧的产气大肠杆菌(GVs-E.coli)。GVs-E.coli 在肿瘤内定植和增殖,而 GVs 则有助于超声成像和合作 PFUS。此外,还开发了含有超顺磁性氧化铁(SPIO,Fe3O4)、全氟己烷(PFH)和表柔比星(EPI)的多功能阳离子聚乙烯亚胺(PEI)-聚乳酸-共聚乙醇酸(PLGA)纳米粒子(PEI-PLGA/EPI/PFH@Fe3O4)。GVs-E.coli通过静电吸附作用,有效引导PEI-PLGA/EPI/PFH@Fe3O4在肿瘤靶区内聚集,从而对肿瘤的根除产生协同治疗作用。总之,GVs-E.coli介导的多功能纳米粒子可与PFUS和化疗协同作用,有效治疗肿瘤,克服了目前FUAS疗法的局限性,提高了安全性和疗效。这种方法为肿瘤治疗提供了一种前景广阔的新策略。
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引用次数: 0
Correction: Conductive single-wall carbon nanotubes/extracellular matrix hybrid hydrogels promote the lineage-specific development of seeding cells for tissue repair through reconstructing an integrin-dependent niche. 更正:导电单壁碳纳米管/细胞外基质杂化水凝胶通过重建依赖整合素的龛位,促进了用于组织修复的播种细胞的特异性发育。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s12951-024-02867-w
Rui Bai, Jianfeng Liu, Jiao Zhang, Jinmiao Shi, Zhigeng Jin, Yi Li, Xiaoyu Ding, Xiaoming Zhu, Chao Yuan, Bingshui Xiu, Huiliang Liu, Zengqiang Yuan, Zhiqiang Liu
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引用次数: 0
Double-camouflaged tellurium nanoparticles for enhanced photothermal immunotherapy of tumor. 用于增强肿瘤光热免疫疗法的双掩蔽碲纳米粒子。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-08 DOI: 10.1186/s12951-024-02853-2
Chaoqing Li, Luyao Yang, Bin Zhang, Jiahao Li, Bingjie Cai, Wei Ni, Guojun Zhang

The photothermal conversion properties of tellurium (Te) nanoparticles have been extensively investigated, rendering them a promising candidate for tumor photothermal therapy. However, there is still room for improvement in the development of efficient Te-based drug delivery systems. Here, Te nanoparticles are mineralized with bioactive molecules within attenuated Salmonella (S-Te), which are subsequently taken up by macrophages (RAW264.7) to construct a double-camouflaged delivery platform (RS-Te). Remarkably, RS-Te retains superior photothermal properties under near-infrared irradiation. The mineralization process eliminates bacterial proliferation potential, thereby mitigating the risk of excessive bacterial growth in vivo. Furthermore, the uptake of bacteria by macrophages not only polarizes them into M1 macrophages to induce an anti-tumor immune response but also circumvents any adverse effects caused by complex antigens on the bacterial surface. The results show that RS-Te can effectively accumulate and retain in tumors. RS-Te-mediated photothermal immunotherapy largely promotes the maturation of dendritic cells and priming of cytotoxic T cells induced by near-infrared laser irradiation. Moreover, RS-Te can switch the activation of macrophages from an immunosuppressive M2 phenotype to a more inflammatory M1 state. The double-camouflaged delivery system may offer highly efficient and safe cancer treatment.

碲(Te)纳米粒子的光热转换特性已得到广泛研究,使其有望成为肿瘤光热疗法的候选物质。然而,在开发基于碲的高效给药系统方面仍有改进的余地。在这里,Te 纳米粒子与减毒沙门氏菌(S-Te)内的生物活性分子矿化在一起,随后被巨噬细胞(RAW264.7)吸收,从而构建了一个双伪装给药平台(RS-Te)。值得注意的是,RS-Te 在近红外照射下仍具有优异的光热特性。矿化过程消除了细菌增殖的可能性,从而降低了细菌在体内过度生长的风险。此外,巨噬细胞吸收细菌后,不仅能将其极化为 M1 型巨噬细胞,诱导抗肿瘤免疫反应,还能避免细菌表面的复杂抗原造成的不良影响。研究结果表明,RS-Te 能有效地在肿瘤内积聚和保留。RS-Te 介导的光热免疫疗法在很大程度上促进了近红外激光照射诱导的树突状细胞的成熟和细胞毒性 T 细胞的启动。此外,RS-Te 还能将巨噬细胞的活化从免疫抑制的 M2 表型转换为更具炎症性的 M1 状态。这种双重伪装递送系统可提供高效、安全的癌症治疗。
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引用次数: 0
Nanomaterial-mediated host directed therapy of tuberculosis by manipulating macrophage autophagy. 通过操纵巨噬细胞的自噬作用,以纳米材料为媒介对结核病进行宿主定向治疗。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-08 DOI: 10.1186/s12951-024-02875-w
Yilin Liu, Jiajun Wang, Jiayi Yang, Jiaojiao Xia, Jiaqi Yu, Dongsheng Chen, Yuhe Huang, Fen Yang, Yongdui Ruan, Jun-Fa Xu, Jiang Pi

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a major public health issue worldwide. Mtb has developed complicated strategies to inhibit the immunological clearance of host cells, which significantly promote TB epidemic and weaken the anti-TB treatments. Host-directed therapy (HDT) is a novel approach in the field of anti-infection for overcoming antimicrobial resistance by enhancing the antimicrobial activities of phagocytes through phagosomal maturation, autophagy and antimicrobial peptides. Autophagy, a highly conserved cellular event within eukaryotic cells that is effective against a variety of bacterial infections, has been shown to play a protective role in host defense against Mtb. In recent decades, the introduction of nanomaterials into medical fields open up a new scene for novel therapeutics with enhanced efficiency and safety against different diseases. The active modification of nanomaterials not only allows their attractive targeting effects against the host cells, but also introduce the potential to regulate the host anti-TB immunological mechanisms, such as apoptosis, autophagy or macrophage polarization. In this review, we introduced the mechanisms of host cell autophagy for intracellular Mtb clearance, and how functional nanomaterials regulate autophagy for disease treatment. Moreover, we summarized the recent advances of nanomaterials for autophagy regulations as novel HDT strategies for anti-TB treatment, which may benefit the development of more effective anti-TB treatments.

由结核分枝杆菌(Mtb)感染诱发的肺结核(TB)仍然是全球重大的公共卫生问题。结核分枝杆菌开发了复杂的策略来抑制宿主细胞的免疫清除,这大大促进了结核病的流行并削弱了抗结核治疗的效果。宿主导向疗法(HDT)是抗感染领域的一种新方法,它通过吞噬体成熟、自噬和抗菌肽来增强吞噬细胞的抗菌活性,从而克服抗菌药耐药性。自噬是真核细胞内的一种高度保守的细胞活动,可有效抵抗多种细菌感染,已被证明在宿主防御 Mtb 的过程中发挥保护作用。近几十年来,纳米材料被引入医疗领域,为针对不同疾病的高效、安全的新型疗法开辟了新的前景。对纳米材料的活性修饰不仅能使其对宿主细胞产生诱人的靶向效应,还能调节宿主的抗结核免疫机制,如细胞凋亡、自噬或巨噬细胞极化。在这篇综述中,我们介绍了宿主细胞自噬清除胞内Mtb的机制,以及功能纳米材料如何调控自噬以治疗疾病。此外,我们还总结了自噬调控纳米材料作为新型 HDT 策略用于抗结核治疗的最新进展,这可能有利于开发更有效的抗结核治疗方法。
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引用次数: 0
The new advance of exosome-based liquid biopsy for cancer diagnosis. 基于外泌体的液体活检在癌症诊断中的新进展。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-08 DOI: 10.1186/s12951-024-02863-0
Haozhou Tang, Dan Yu, Jiahui Zhang, Maoye Wang, Min Fu, Yu Qian, Xiaoxin Zhang, Runbi Ji, Jianmei Gu, Xu Zhang

Liquid biopsy is a minimally invasive method that uses biofluid samples instead of tissue samples for cancer diagnosis. Exosomes are small extracellular vesicles secreted by donor cells and act as mediators of intercellular communication in human health and disease. Due to their important roles, exosomes have been considered as promising biomarkers for liquid biopsy. However, traditional methods for exosome isolation and cargo detection methods are time-consuming and inefficient, limiting their practical application. In the past decades, many new strategies, such as microfluidic chips, nanowire arrays and electrochemical biosensors, have been proposed to achieve rapid, accurate and high-throughput detection and analysis of exosomes. In this review, we discussed about the new advance in exosome-based liquid biopsy technology, including isolation, enrichment, cargo detection and analysis approaches. The comparison of currently available methods is also included. Finally, we summarized the advantages and limitations of the present strategies and further gave a perspective to their future translational use.

液体活检是一种微创方法,利用生物流体样本代替组织样本进行癌症诊断。外泌体是供体细胞分泌的小细胞外囊泡,是人类健康和疾病中细胞间通信的媒介。由于其重要作用,外泌体一直被认为是液体活检中很有前景的生物标记物。然而,传统的外泌体分离和货物检测方法耗时长、效率低,限制了它们的实际应用。在过去的几十年里,人们提出了许多新的策略,如微流控芯片、纳米线阵列和电化学生物传感器等,以实现快速、准确和高通量的外泌体检测和分析。在这篇综述中,我们讨论了基于外泌体的液体活检技术的新进展,包括分离、富集、货物检测和分析方法。我们还对目前可用的方法进行了比较。最后,我们总结了现有策略的优势和局限性,并进一步展望了其未来的转化应用。
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引用次数: 0
Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice. 口服携带 CX5461 的槐花外泌体纳米颗粒可改善 DSS 诱导的小鼠结肠炎。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-08 DOI: 10.1186/s12951-024-02856-z
Manqi Zhang, Xichao Xu, Liqian Su, Yuqing Zeng, Jingxiong Lin, Wenwen Li, Yigui Zou, Sicong Li, Boxian Lin, Ziyuan Li, Hu Chen, Yuheng Huang, Quanle Xu, Hongbo Chen, Fang Cheng, Dongling Dai

Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1β, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.

溃疡性结肠炎(UC)属于慢性炎症性疾病,具有复发性的特点。治疗溃疡性结肠炎的传统口服药物在临床上受到胃肠道过早降解、疗效不佳和不良反应等限制。CX5461 可治疗自身免疫性疾病、免疫排斥和血管炎症。然而,低溶解度、静脉注射和非炎症靶向性限制了其临床应用。在此,本研究旨在开发携带 CX5461 的 Sophora Flavescens 衍生外泌体纳米颗粒(SFELNVs@CX5461),用于口服 CX5461 治疗 UC。我们发现 SFELNVs 具有纳米直径(80 nm)和负 zeta 电位(-32mV)。细胞吸收表明,SFELNVs 可被巨噬细胞靶向吸收,从而提高药物浓度。此外,口服 SFELNVs@CX5461 在右旋糖酐硫酸钠(DSS)诱导的结肠炎小鼠胃肠道中表现出良好的安全性和稳定性,以及炎症靶向能力。在体内,口服 SFELNVs 和 CX5461 可以缓解小鼠结肠炎。更重要的是,SFELNVs和CX5461通过抑制促炎因子(TNF-α、IL-1β和IL-6)的表达和促进M2巨噬细胞极化,缓解了小鼠结肠炎。此外,利用 miRNA 测序,SFELNVs 通过 miR4371c 促进了 M2 极化。我们的研究结果表明,SFELNVs@CX5461是一种可改善结肠炎的新型口服治疗药物,也是一种安全治疗UC的靶向策略。
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引用次数: 0
Nanobiotechnology boosts ferroptosis: opportunities and challenges. 纳米生物技术促进铁蛋白沉积:机遇与挑战。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-08 DOI: 10.1186/s12951-024-02842-5
Shiqi Han, Jianhua Zou, Fan Xiao, Jing Xian, Ziwei Liu, Meng Li, Wei Luo, Chan Feng, Na Kong

Ferroptosis, distinct from apoptosis, necrosis, and autophagy, is a unique type of cell death driven by iron-dependent phospholipid peroxidation. Since ferroptosis was defined in 2012, it has received widespread attention from researchers worldwide. From a biochemical perspective, the regulation of ferroptosis is strongly associated with cellular metabolism, primarily including iron metabolism, lipid metabolism, and redox metabolism. The distinctive regulatory mechanism of ferroptosis holds great potential for overcoming drug resistance-a major challenge in treating cancer. The considerable role of nanobiotechnology in disease treatment has been widely reported, but further and more systematic discussion on how nanobiotechnology enhances the therapeutic efficacy on ferroptosis-associated diseases still needs to be improved. Moreover, while the exciting therapeutic potential of ferroptosis in cancer has been relatively well summarized, its applications in other diseases, such as neurodegenerative diseases, cardiovascular and cerebrovascular diseases, and kidney disease, remain underreported. Consequently, it is necessary to fill these gaps to further complete the applications of nanobiotechnology in ferroptosis. In this review, we provide an extensive introduction to the background of ferroptosis and elaborate its regulatory network. Subsequently, we discuss the various advantages of combining nanobiotechnology with ferroptosis to enhance therapeutic efficacy and reduce the side effects of ferroptosis-associated diseases. Finally, we analyze and discuss the feasibility of nanobiotechnology and ferroptosis in improving clinical treatment outcomes based on clinical needs, as well as the current limitations and future directions of nanobiotechnology in the applications of ferroptosis, which will not only provide significant guidance for the clinical applications of ferroptosis and nanobiotechnology but also accelerate their clinical translations.

有别于细胞凋亡、坏死和自噬的铁变性是一种由铁依赖性磷脂过氧化驱动的独特细胞死亡类型。自 2012 年铁凋亡被定义以来,它受到了全球研究人员的广泛关注。从生物化学的角度来看,铁吞噬的调控与细胞代谢密切相关,主要包括铁代谢、脂代谢和氧化还原代谢。铁突变的独特调控机制为克服耐药性--治疗癌症的主要挑战--提供了巨大潜力。纳米生物技术在疾病治疗中的巨大作用已被广泛报道,但关于纳米生物技术如何提高铁氧化相关疾病的疗效,仍有待进一步和更系统的讨论。此外,虽然人们已相对较好地总结了铁蛋白沉积在癌症中令人振奋的治疗潜力,但其在其他疾病(如神经退行性疾病、心脑血管疾病和肾脏疾病)中的应用仍未得到充分报道。因此,有必要填补这些空白,进一步完善纳米生物技术在铁突变中的应用。在这篇综述中,我们广泛介绍了铁突变的背景并阐述了其调控网络。随后,我们讨论了纳米生物技术与铁变态反应相结合的各种优势,以提高疗效并减少铁变态反应相关疾病的副作用。最后,我们根据临床需求,分析讨论了纳米生物技术和铁蛋白病在改善临床治疗效果方面的可行性,以及纳米生物技术在铁蛋白病应用中的目前局限性和未来发展方向,这不仅将为铁蛋白病和纳米生物技术的临床应用提供重要指导,还将加速其临床转化。
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引用次数: 0
Zinc-based Polyoxometalate Nanozyme Functionalized Hydrogels for optimizing the Hyperglycemic-Immune Microenvironment to Promote Diabetic Wound Regeneration. 锌基多氧金属酸盐纳米酶功能化水凝胶用于优化高血糖-免疫微环境以促进糖尿病伤口再生
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-08 DOI: 10.1186/s12951-024-02840-7
Chaoyu Pu, Yong Wang, Honglin Xiang, Jiangtao He, Qiyuan Sun, Yuan Yong, Lu Chen, Ke Jiang, Hanfeng Yang, Yuling Li

Background: In diabetic wounds, hyperglycemia-induced cytotoxicity and impaired immune microenvironment plasticity directly hinder the wound healing process. Regulation of the hyperglycemic microenvironment and remodeling of the immune microenvironment are crucial.

Results: Here, we developed a nanozymatic functionalized regenerative microenvironmental regulator (AHAMA/CS-GOx@Zn-POM) for the effective repair of diabetic wounds. This novel construct integrated an aldehyde and methacrylic anhydride-modified hyaluronic acid hydrogel (AHAMA) and chitosan nanoparticles (CS NPs) encapsulating zinc-based polymetallic oxonate nanozyme (Zn-POM) and glucose oxidase (GOx), facilitating a sustained release of release of both enzymes. The GOx catalyzed glucose to gluconic acid and (H₂O₂), thereby alleviating the effects of the hyperglycemic microenvironment on wound healing. Zn-POM exhibited catalase and superoxide dismutase activities to scavenge reactive oxygen species and H₂O₂, a by-product of glucose degradation. Additionally, Zn-POM induced M1 macrophage reprogramming to the M2 phenotype by inhibiting the MAPK/IL-17 signaling diminishing pro-inflammatory cytokines, and upregulating the expression of anti-inflammatory mediators, thus remodeling the immune microenvironment and enhancing angiogenesis and collagen regeneration within wounds. In a rat diabetic wound model, the application of AHAMA/CS-GOx@Zn-POM enhanced neovascularization and collagen deposition, accelerating the wound healing process.

Conclusions: Therefore, the regenerative microenvironment regulator AHAMA/CS-GOx@Zn-POM can achieve the effective conversion of a pathological microenvironment to regenerative microenvironment through integrated control of the hyperglycemic-immune microenvironment, offering a novel strategy for the treatment of diabetic wounds.

背景:在糖尿病伤口中,高血糖诱导的细胞毒性和受损的免疫微环境可塑性直接阻碍了伤口愈合过程。调节高血糖微环境和重塑免疫微环境至关重要:在此,我们开发了一种纳米酶功能化再生微环境调节剂(AHAMA/CS-GOx@Zn-POM),用于有效修复糖尿病伤口。这种新型结构整合了醛和甲基丙烯酸酐改性透明质酸水凝胶(AHAMA)和壳聚糖纳米颗粒(CS NPs),其中封装了锌基多金属氧膦酸盐纳米酶(Zn-POM)和葡萄糖氧化酶(GOx),促进了两种酶的持续释放。葡萄糖氧化酶可将葡萄糖催化成葡萄糖酸和(H₂O₂),从而减轻高血糖微环境对伤口愈合的影响。Zn-POM 具有过氧化氢酶和超氧化物歧化酶活性,可清除活性氧和葡萄糖降解的副产物 H₂O₂。此外,Zn-POM 还能抑制 MAPK/IL-17 信号转导,减少促炎细胞因子,上调抗炎介质的表达,从而诱导 M1 巨噬细胞重编程为 M2 表型,从而重塑免疫微环境,促进伤口内的血管生成和胶原再生。在大鼠糖尿病伤口模型中,AHAMA/CS-GOx@Zn-POM 的应用促进了血管新生和胶原沉积,加速了伤口愈合过程:因此,再生微环境调节剂 AHAMA/CS-GOx@Zn-POM 可通过综合控制高血糖免疫微环境,实现病理微环境向再生微环境的有效转化,为糖尿病伤口的治疗提供了一种新策略。
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引用次数: 0
Ultrasound-responsive nanocarriers with siRNA and Fe3O4 regulate macrophage polarization and phagocytosis for augmented non-small cell lung cancer immunotherapy. 含有 siRNA 和 Fe3O4 的超声响应纳米载体能调节巨噬细胞的极化和吞噬作用,从而增强非小细胞肺癌的免疫疗法。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-07 DOI: 10.1186/s12951-024-02883-w
Ming Li, Yuanyuan Li, Jun Zheng, Zhen Ma, Jianye Zhang, Hao Wu, Yangyang Zhu, Pan Li, Fang Nie

The immunosuppressive tumor microenvironment (TME) significantly inhibits the effective anti-tumor immune response, greatly affecting the efficacy of immunotherapy. Most tumor-associated macrophages (TAMs) belong to the M2 phenotype, which contributes significantly to the immunosuppressive effects in non-small cell lung cancer (NSCLC) TME. The interaction between signal regulatory protein α (SIRPα) expressed on macrophages and CD47, a transmembrane protein overexpressed on cancer cells, activates the "eat-me-not" signaling pathway, inhibiting phagocytosis. In this study, a folic acid (FA)-modified ultrasound responsive gene/drugs delivery system, named FA@ PFP @ Fe3O4 @LNB-SIRPα siRNA (FA-PFNB-SIRPα siRNA), was developed using 1,2-dioleoacyl-3-trimethylammonium-propane (DOTAP), FA-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino (polyethylene glycol)2000] (DSPE-PEG2000-FA), cholesterol, and perfluoropentane (PFP), for the delivery of siRNA encoding SIRPα mRNA and immune adjuvant Fe3O4 nanoparticles. Under ultrasound conditions, the nanobubbles effectively transfected macrophages, inhibiting SIRPα mRNA and protein expression, promoting the phagocytosis of TAMs, and synergistically reversing M2 polarization. This system promotes the infiltration of T cells, enhances the proliferation and activation of cytotoxic T cells, and inhibits the infiltration of immunosuppressive cells in tumor tissues. Administration of FA-PFNB-SIRPα siRNA combined with ultrasound significantly inhibits NSCLC progression. The study highlights the potential of ultrasound nanotechnology-enabled delivery of SIRPα siRNA and Fe3O4 as an effective strategy for macrophage-based immunotherapy to reshape the immunosuppressive TME for cancer therapy.

免疫抑制性肿瘤微环境(TME)严重抑制了有效的抗肿瘤免疫反应,极大地影响了免疫疗法的疗效。大多数肿瘤相关巨噬细胞(TAMs)属于M2表型,这在很大程度上导致了非小细胞肺癌(NSCLC)TME的免疫抑制效应。巨噬细胞上表达的信号调控蛋白α(SIRPα)与癌细胞上过度表达的跨膜蛋白CD47相互作用,激活了 "吃我不吃 "信号通路,抑制了吞噬作用。本研究开发了一种叶酸(FA)修饰的超声响应基因/药物递送系统,命名为 FA@ PFP @ Fe3O4 @LNB-SIRPα siRNA(FA-PFNB-SIRPα siRNA),该系统利用 1,2-二油酰基-3-三甲基铵丙烷(DOTAP)、FA-1、2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino (polyethylene glycol)2000] (DSPE-PEG2000-FA)、胆固醇和全氟戊烷 (PFP),用于递送编码 SIRPα mRNA 的 siRNA 和免疫佐剂 Fe3O4 纳米颗粒。在超声条件下,纳米气泡能有效转染巨噬细胞,抑制 SIRPα mRNA 和蛋白的表达,促进 TAMs 的吞噬,并协同逆转 M2 极化。该系统能促进 T 细胞的浸润,增强细胞毒性 T 细胞的增殖和活化,抑制肿瘤组织中免疫抑制细胞的浸润。FA-PFNB-SIRPα siRNA 与超声波结合使用能显著抑制 NSCLC 的进展。该研究强调了利用超声纳米技术递送 SIRPα siRNA 和 Fe3O4 作为基于巨噬细胞的免疫疗法的有效策略,重塑免疫抑制 TME 以治疗癌症的潜力。
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引用次数: 0
Biomimetic nanocarriers in cancer therapy: based on intercellular and cell-tumor microenvironment communication. 生物仿生纳米载体在癌症治疗中的应用:基于细胞间和细胞与肿瘤微环境的交流。
IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-06 DOI: 10.1186/s12951-024-02835-4
He Mengyuan, Li Aixue, Gu Yongwei, Chai Qingqing, Cai Huanhuan, Liu Xiaoyan, Liu Jiyong

Inspired by the concept of "natural camouflage," biomimetic drug delivery systems have emerged to address the limitations of traditional synthetic nanocarriers, such as poor targeting, susceptibility to identification and clearance, inadequate biocompatibility, low permeability, and systemic toxicity. Biomimetic nanocarriers retain the proteins, nucleic acids, and other components of the parent cells. They not only facilitate drug delivery but also serve as communication media to inhibit tumor cells. This paper delves into the communication mechanisms between various cell-derived biomimetic nanocarriers, tumor cells, and the tumor microenvironment, as well as their applications in drug delivery. In addition, the additional communication capabilities conferred on the modified biomimetic nanocarriers, such as targeting and environmental responsiveness, are outlined. Finally, we propose future development directions for biomimetic nanocarriers, hoping to inspire researchers in their design efforts and ultimately achieve clinical translation.

受 "自然伪装 "概念的启发,生物仿生给药系统应运而生,以解决传统合成纳米载体的局限性,如靶向性差、易被识别和清除、生物相容性不足、渗透性低和全身毒性等。仿生纳米载体保留了母细胞的蛋白质、核酸和其他成分。它们不仅有利于药物输送,还可作为抑制肿瘤细胞的交流媒介。本文深入探讨了各种源自细胞的生物仿生纳米载体、肿瘤细胞和肿瘤微环境之间的交流机制,以及它们在给药方面的应用。此外,本文还概述了改良生物仿生纳米载体所具有的额外通信能力,如靶向性和环境响应性。最后,我们提出了仿生纳米载体未来的发展方向,希望能对研究人员的设计工作有所启发,并最终实现临床转化。
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Journal of Nanobiotechnology
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