CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Zhihuang Zhang,Yan Peng,Liyan Qiu
The enrichment of M2-phenotype tumor-associated macrophages (TAMs) is the main factor to create an immunosuppressive microenvironment, which seriously attenuates antitumor treatment. Herein, we explored the capability of rigid nanoparticles to reprogram TAMs to the M1-like phenotype via mechanical force. We designed and synthesized amphiphilic copolymer PLA- b -PItEG initiated by the HO-Pd(II) complex. In contrast to polyethylene glycol, the hydrophilic PItEG segments have a helical conformation, which endows the self-assembled PLA- b -PItEG nanoparticles with stiff surface characteristics of higher Young’s modulus and hydrophobicity. The rigid nanoparticles displayed strong interaction with TAMs to produce greater deformation of cell membrane and activated mechanosensitive potassium ion channel. Consequently, rigid nanoparticles exerted a positive effect on the proinflammatory polarization of TAMs. The expression level of CD86, a typical M1 macrophage marker, was increased by 60% compared with that in the soft PEG-NP group while CD206, a typical M2 macrophage marker, was decreased. Furthermore, several M1-related cytokines such as TNF-α, IL12p40, IL-6 and IL-1β were upregulated. In vitro and in vivo immune responses triggered by rigid nanoparticles could significantly inhibit B16F10 tumor growth with 71.44% tumor inhibitory rate. This study offers new insight into the use of mechanical forces for tumor immunotherapy.
研究领域:
纳米技术
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免疫治疗
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癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Yushi Zhang,Xuya Yu,Lingpeng Luo,Yigang Xu,Hanjie Zhang,Zhuo Mao,Yuqin Zhang,Cuihong Yang,Lu Wang,Pengcheng Zhang,Sitong Li,Meitong Ou,Ran Luo,Dunwan Zhu,Wen Li,Lin Mei
Immunotherapy, a pivotal and promising approach for tumor treatment, has demonstrated prominent clinical efficacy. However, its effectiveness is often impeded by insufficient antitumor immune responses attributed to the immunosuppressive tumor microenvironment (TME). The combination of immune activation through the stimulator of interferon genes (STING) pathway and phototherapy holds great potential for surmounting this challenge in advanced tumor immunotherapy. Herein, a novel manganese-boosted NIR-II photo-metalloimmunotherapy is proposed to synergistically enhance antitumour efficacy by fabricating Mn 2+ -BODIPY-based coordinated photo-immune nanoadjuvants (BMR), modified with tumor-targeted peptide cRGD. The obtained BMR could effectively deliver Mn 2+ to tumor sites, and immunogenic cell death (ICD) was evoked by localized photothermal ablation of tumors using NIR-II laser irradiation. Simultaneously, pH-responsive release of Mn 2+ would trigger the activation of STING pathway to promote the production of type I interferons (I-IFNs), significantly facilitating the maturation of dendritic cells (DCs) and polarization of macrophages to M1 phenotypes. Furthermore, by synergistically initiating systematic and robust antitumour immune responses, the BMR-mediated NIR-II photo-metalloimmunotherapy achieved remarkable therapeutic efficacy against both primary and lung metastasis of B16F10 tumors. Overall, in light of the versatile functionalities and synthetic flexibility of coordinated nanoadjuvants, formulated with photofunctional ligands and diverse metal ions, this work provides new insights into the design of metal coordination nanomedicine for effective antitumor photo-metalloimmunotherapy.
研究领域:
癌症治疗
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纳米技术
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免疫学
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光疗
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Huapan Fang,Linfu Chen,Zheng Deng,Yunxuan Gao,Yang Yang,Qian Chen,Zhuang Liu
Oral administration of protein drugs has always been challenging owing to various intestinal barriers. Herein, we developed an efficient oral protein delivery strategy by using in situ polymerization of zwitterions to encapsulate proteins, which were then loaded into enteric coated capsules for oral feeding. After oral administration of such capsules, the enteric coating would be degraded once the capsule enters the intestine, releasing polyzwitterion/protein nanocomplexes. With the help of polyzwitterion modification, such nanocomplexes were able to pass through the mucus and cellular barriers, likely by the proton-assisted amino acid transporter 1 (PAT1) pathway. Such a polyzwitterion-based protein encapsulation strategy could allow for effective oral delivery of different proteins, including bovine serum albumin (BSA), insulin, and antibodies. Using this strategy, the oral bioavailabilities of insulin and immunoglobin G (IgG) were measured to be as high as 16.9% and 12.5%, respectively. Notably, oral feeding of polyzwitterion/insulin capsules could effectively lower the blood glucose level of diabetic animals (mice, rats, and pigs). Moreover, polyzwitterion/antiprogramed death-1 (αPD-1) capsules were able to induce efficient antitumor immune responses, showing significant tumor inhibition effects toward B16F10- and 4T1-tumor bearing mouse models after oral administration. No significant toxic effect was observed for such oral protein formulations in the treated animals. Our work presents a strategy for the efficient oral delivery of protein drugs, including those with large molecular weights (e.g., antibodies) that can hardly be orally delivered using existing technologies.
研究领域:
药学
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生物技术
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药物递送系统
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蛋白质工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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