JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Chen Shang,He Yan,Huang Xin,Shen Yao,Zou Qingshuang,Yang Gun,Fu Li,Liu Quan,Luo Dixian
Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract
研究领域:
癌症生物学
·
纳米技术
·
免疫疗法
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Manxiang Wu,Dong Xie,Lianfu Wang,Zhusheng Liu,Hongying Bao,Tao Ye,Chengyuan Hong,Jie Lin,Tianxiang Chen,Aiguo Wu,Qiang Li
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Its pathogenesis involves aberrant activation and aggressive proliferation of fibroblast-like synoviocytes (FLS), excessive macrophage infiltration, and disrupted M1/M2 macrophage polarization within the synovial microenvironment (SME). However, current therapies remain inadequate for precise SME modulation, often leading to limited efficacy and poor prognosis. To address this challenge, we developed a multifunctional nanocapsule, termed RP/HP@Mn/L, which is composed of a low molecular weight heparin (LMWH)-modified, Mn 2+ -doped hollow mesoporous polydopamine (HP) nanocarrier co-loaded with rapamycin (Rap) and paeoniflorin (Pae). This nanocapsule's dual-ligand strategy targets P-selectin on inflamed endothelial cells and integrin αM on inflammatory macrophages, enabling precise spatiotemporal accumulation at the pathological site. This nanocapsule enables spatiotemporally specific targeting of both inflammatory endothelial cells and inflammatory macrophages, thereby enhancing precise drug delivery to pathological sites. Mechanistic investigations revealed that RP/HP@Mn/L, in combination with mild photothermal therapy (PTT) mediated by HP, effectively suppressed FLS proliferation and invasion. Concurrently, it promoted the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. These synergistic effects facilitated the remodeling of the SME, thereby alleviating synovitis and enhancing bone repair in RA. In conclusion, this study proposes a spatiotemporally targeted combinatorial nanotherapeutic strategy that integrates multimodal mechanisms for SME modulation. This approach represents a promising therapeutic platform for improving outcomes in RA and other autoimmune disorders.
研究领域:
纳米医学
·
免疫治疗
·
风湿病学
·
生物医学工程
·
药物递送系统
·
炎症性疾病
·
自身免疫性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Yuanqi Chen,Kezheng Lei,Yinxi Li,Zhixiang Mu,Tengda Chu,Jiajun Hu,Bairui Zeng,Yi Wang,Jianliang Shen,Xiaojun Cai,Tianpeng Shi,Hui Deng
Oral mucosal wounds are more prone to inflammation due to direct exposure to various microorganisms. This can result in pain, delayed healing, and other complications, affecting patients' daily activities such as eating and speaking. Consequently, the overall quality of life for patients is significantly reduced. To address these challenges, we developed a multifunctional therapeutic nanoplatform, DATS@Arg-EA-SA, through the self-assembly of guanidinated dendritic peptides (Arg-EA-SA) that encapsulate diallyl trisulfide (DATS), a hydrogen sulfide (H 2 S) donor. The guanidine-rich surface of DATS@Arg-EA-SA efficiently neutralizes reactive oxygen species (ROS) in the ulcer microenvironment, generating nitric oxide (NO), which acts as the primary antimicrobial agent by disrupting bacterial membranes. Concurrently, the presence of glutathione triggers the release of H 2 S from DATS, providing supplementary antibacterial support. DATS@Arg-EA-SA effectively kills all bacteria, achieving results comparable to those of penicillin, a classical antibiotic. Moreover, it demonstrates superior sterilization efficacy against drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), significantly outperforming penicillin. Following the initial antimicrobial phase, the nanoplatform transitions into an anti-inflammatory stage. H 2 S, in synergy with NO, facilitates the conversion of M1 macrophages to M2 macrophages, thereby reducing the expression of inflammatory factors. Importantly, the combination of H 2 S and NO provides effective analgesia by downregulating the expression of TRPV1 and TRPV4, thus restoring normal dietary behaviors and improving the overall quality of life. This system ultimately promotes collagen fiber deposition and accelerates the re-epithelialization of the ulcer wound, positioning DATS@Arg-EA-SA as a promising gas-delivery nanoplatform for rapid wound repair in the clinical treatment. Statement of Significance Oral mucosal wounds are highly susceptible to microbial infections, leading to inflammation, pain, delayed healing, and a significant decline in quality of life. We developed a multifunctional therapeutic nanoplatform (DATS@Arg-EA-SA) via the self-assembly of guanidinated dendritic peptides encapsulating the H 2 S donor DATS, which exhibited antibacterial, anti-inflammatory, and analgesic properties. In the oral ulcer microenvironment, DATS@Arg-EA-SA generates substantial NO under elevated ROS levels, while glutathione triggers the controlled release of H 2 S. NO disrupts bacterial membranes as the primary antibacterial agent, with H 2 S providing synergistic antibacterial effects. Furthermore, H 2 S and NO synergistically promote the transformation of M1 to M2 macrophages, attenuating inflammation. Importantly, the combined action of H 2 S and NO alleviates pain by downregulating TRPV1 and TRPV4, supporting the restoration of normal dietary behavior and improving quality of life.
研究领域:
药学
·
纳米技术
·
生物材料
·
医学
·
牙科
·
炎症研究
·
伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yuhuan Li,Jiayin Lv,Shuchen Liu,Zhuoran Wang,Yu Gao,Zheyuan Fan,Lei Huang,Jing Cui,Boya Zhang,Xinchen Liu,Zhuo Zhang,Te Liu,Daowei Li,Modi Yang
The role of pro-inflammatory macrophages (M1) in rheumatoid arthritis (RA) is significant, as they produce excessive cytokines. Targeting efferocytosis is a potential manner to repolarize M1 macrophages into pro-resolving M2 phenotype, which restores immune homeostasis by releasing anti-inflammatory mediators. In this study, liquid nitrogen-treated dead macrophages (DM) are employed to act as a dead cell-derived active targeted drug carrier for shikonin (SHK) and induce efferocytosis in M1 macrophages with the enhancement of SHK as an AMP-activated protein kinase (AMPK)-activator. The synergistic activation of AMPK leads to uncoupled protein 2 (UCP2) upregulation and reprograms M1 macrophages into M2 phenotypes by promoting oxidative phosphorylation. In the mouse model of collagen-induced arthritis, the intravenous administration of DM/SHK leads to a consistent transformation of M1 macrophages into the M2 phenotype within the infiltrative synovium. This transformation of macrophages results in the restoration of immune homeostasis in the synovium through an increase in the production of pro-resolving mediators. Additionally, it inhibits synovial proliferation and infiltration and provides protection against erosion of cartilage and bone. In summary, LNT-based DM serves as an active targeting drug carrier to M1 macrophages and also acts synergistically with SHK to target immunometabolism.
研究领域:
免疫学
·
药理学
·
风湿病学
·
炎症
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Shuhui Chen,Xin Zhang,Guangbing Luo,Qiuyuan Zhao,Jie shen,Jiamian Zhan,Qing Xie,Shaofeng Hua,Honghao Hou,Yutong He,Xiaozhong Qiu
To overcome the limitations of current cardiac patches in comprehensively treating post-infarction ventricular remodeling, a paradigm-shifting orchestrated adhesive anisotropic/anti-adhesive isotropic Janus conductive patch (AGMM/PDP) integrated with mitochondria-targeted nanoparticles (MSNs/P/M) is introduced. The anisotropic AGMM layer enables suture-free tissue integration via covalent/non-covalent bonding, while the PDP layer forms a superhydrophilic antifouling barrier preventing postoperative adhesions. Simultaneously, MSNs/P/M nanoparticles achieve unprecedented mitochondrial salvage, leveraging polydopamine homing and melatonin synergy for enhanced mitochondrial affinity and efficient lysosomal escape, effectively preserving ultrastructure, membrane potential, and restoring oxidative phosphorylation to increase ATP production 1.8-fold under hypoxia. Therapeutically, this integrated system orchestrates synchronized multi-scale repair: acutely scavenging reactive oxygen species (ROS) (94% reduction), subsequently driving M1-to-M2 macrophage polarization to mitigate inflammation and stimulate angiogenesis (4.4-fold increased vascular density), and chronically restoring anisotropic conduction (55% increased velocity) and mechanical synchrony via transcriptomic reprogramming (upregulating energy/contractile genes; downregulating fibrosis/inflammation markers). This synergistically reversed ventricular remodeling in vivo, evidenced by 25% improved ejection fraction, 3.5-fold reduced fibrosis, and suppressed arrhythmias, collectively establishing a transformative. The developed patch presents a comprehensive Janus therapeutic strategy by mimicking the structural anisotropy native cardiac tissue while conferring mechanical isotropy, by inhibiting fibrosis, by restoring bioenergetics, which more effectively promotes cardiac functional recovery.
研究领域:
生物医学工程
·
心脏组织工程
·
纳米医学
·
再生医学
·
电生理学
·
线粒体生物学
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Wentao Wang,Zhenyu Li,Siming Zhang,Yue Ma,Lei Yu,Qidong Zhang,Guoqing Pan,Dechun Geng,Chen Zhu,Jiaxiang Bai
The reduced initial stability of orthopedic implants in osteoporotic bone matrices, coupled with excessive M1 macrophage polarization at bone-implant interfaces, disrupt bone–immune homeostasis and vascularization, ultimately leading to implant loosening or failure. Inspired by the marine mussel Mytilus edulis foot protein (Mefp), a pH-responsive multifunctional bone glue (YDC-Gel-Zn) with broad-spectrum adhesion capabilities is developed for osteoporotic bone-implant integration. This pseudo-Mefp bioglue enables dual-interface adhesion via catechol-rich sequences that mediate stable metal-phenolic coordination with metallic implants and hydrogen-bonded/Michael addition-driven interactions with the bone matrix, thereby improving initial implant fixation. Under osteoporotic inflammatory microenvironments, sequential dissociation of borate ester bonds and metal‒phenolic coordination facilitates the controlled release of Zn 2 ⁺ and proangiogenic/osteogenic peptides (YDC). The released Zn 2 ⁺ remodels glutathione metabolism through glutathione S-transferase (GST)-mediated regulation of glutathione (GSH) levels, inhibits JAK1/STAT1/NLRP3 inflammasome activation, and suppresses the release of proinflammatory cytokines from senescent M1 macrophages, recalibrating the osteo-vascular-immune microenvironment. Due to its positive effects on bone regeneration and angiogenesis, the bioinspired bone bioglue demonstrated a 194% increase in fixation strength in osteoporotic rat models, achieving 93% healthy bone-implant stability. Overall, this study provides a clinically translatable strategy for stable implantation under osteoporotic conditions through synergistic mechanical adaptation, bioactivity regulation, and smart environmental responsiveness.
研究领域:
生物医学工程
·
生物材料
·
组织工程
·
骨科
·
免疫调节
·
再生医学
·
生物粘合剂
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 44
·22615-22627
·
IF 6.895
Ao Hu,Xiaobing Chen,Qunjie Bi,Yang Xiang,Rongrong Jin,Hua Ai,Yu Nie
Polarization regulation of tumor-association macrophages (TAMs) is a promising treatment method for tumors, but aiming at TAMs alone shows unsatisfactory therapeutic efficiency. Therefore, we designed a parallel and cascade control system for both macrophage polarization and tumor cell inhibition. The system is composed of cationic lipopeptides with an arginine-rich periphery (RLS) and anionic magnetic nanoparticles (MNPs) for fleet transfection of miR-125b. Based on the highly efficient magnetofection, miR-125b successfully shows a parallel effect on both M1, promoting polarization by targeting interferon regulatory factor 4 (IRF4) in macrophages, and tumor cell inhibition, by targeting ETS proto-oncogene 1 and cyclin- J. The cascading effect on M1-associated genes is upregulated by up to two orders of magnitude, while M2-associated genes are downregulated. Meanwhile, MNPs also have an effect on the TAM polarization and 4T1 tumor cell inhibition via inflammatory related gene expression and Fenton reaction. Further mimicking the co-culture of RAW264.7 and 4T1 cells in vitro confirmed the synergistic therapy effect. In the treatment of orthotopic breast cancer in mice, considerable M1 macrophage polarization was observed in the RM125b treated group, showing distinct tumor-suppressive effects, with a tumor weight reduction of 60% and tumor metastasis suppression of 50%.
研究领域:
肿瘤学
·
生物医学工程
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）