ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xin Huang,Jiawei Zhu,Chuhuang Dong,Yuqing Li,Qing Yu,Xuan Wang,Zhejie Chen,Jiabei Li,Yu Yang,Haifang Wang
Ag2S quantum dots (QDs) show superior optical properties in the NIR-II region and display significant clinical potential with favorable biocompatibility. However, inherent defects of low targeting and poor solubility necessitate practical modification methods to achieve the theranostics of Ag2S QDs. Herein, we used rolling circle amplification (RCA) techniques to obtain long single-stranded DNA containing the PD-L1 aptamer and C-rich DNA palindromic sequence. The C-rich DNA palindromic sequences can specifically chelate Ag2+ and thus serve as a template to result in biomimetic mineralization and formation of pApt-Ag2S QDs. These QDs enable specific targeting and illuminate hot tumors with high PD-L1 expression effectively, serving as excellent molecular targeted probes. In addition, due to the high NIR-II absorption of Ag2S QDs, pApt-Ag2S QDs exhibit remarkable photothermal properties. And besides, polyvalent PD-L1 aptamers can recognize PD-L1 protein and effectively block the inhibitory signal of PD-L1 on T cells, enabling efficient theranostics through the synergistic effect of photothermal therapy and immune checkpoint blocking therapy. Summary, we enhance the biological stability and antibleaching ability of Ag2S QDs using long single-stranded DNA as a template, thereby establishing a theranostic platform that specifically targets PD-L1 high-expressing inflamed tumors and demonstrates excellent performance both in vitro and in vivo.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2022
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IF 8.663
Ruirui Zhang,Liping Zhong,Xiuli Liu,Xiyu Liu,Qiaoying Chen,Pan Wu,Jian He,Yongmei Li,Yongxiang Zhao,Ziqun Liu,Yan Zu,Yong Huang,Bing Wang
Immunotherapy has made encouraging progress in the field of cancer treatment. Among them, the programmed cell death-ligand 1 (PD-L1) antibody-mediated immunotherapy has stimulated the development of various carrier delivery systems. Inspired by related researchs, in this study, we prepare core-shell structured poly(lactide-co-glycolide) (PLGA) microcapsules as a drug delivery system through microfluidics technology, loaded with PD-L1 aptamers and chemotherapy drug docetaxel. The PD-L1 aptamer loaded in the nuclear layer binds to the PD-L1 molecule produced by tumor cells, blocking the immune checkpoint protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway. As a result, phagocytosis of tumor cells is promoted by using lipopolysaccharide (LPS) induced tumor associated macrophages. Furthermore, docetaxel in the shell is further released, inhibiting tumor cell growth as the PLGA microcapsules degrade. More importantly, the combination of PD-L1 aptamers and the chemotherapy drug docetaxel improved the immune response of the tumor. It showed significant anti-tumor activity and reduced systemic side effects in the melanoma model. At present, more and more nucleic acid aptamers as affinity reagents that can replace antibodies have been used to improve tumor treatment. Therefore, this therapeutic strategy provides more possibilities for tumor treatment by combining aptamer molecules with chemotherapy drugs when exploring more effective combination drugs.
研究领域:
癌症治疗
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药物递送系统
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免疫学
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制药学
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2025
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IF 12.9
Hao Tian,Hongpei Deng,Xinlong Liu,Chang Liu,Chuan Zhang,Kam W. Leong,Jing Ruan,Xianqun Fan
Uveal melanoma (UM) is the most prevalent primary ocular malignancy in adults, with high lethality and limited effective treatment options. Despite identified driver mutations in GNAQ , GNA11 , and BAP1 , therapeutic advancements have been minimal. This study highlights the pivotal role of N6-methyladenosine (m 6 A) modifications in UM pathogenesis and progression, focusing on the demethylase FTO as a therapeutic target. Elevated FTO expression in UM tissues correlates with decreased m 6 A levels, increased aggressiveness, and poor prognosis. The FTO inhibitor meclofenamic acid (MA) restored m 6 A levels, upregulated SLC7A11, and induced disulfidptosis, a unique form of cell death triggered by GSH depletion and NADPH consumption. To address MA's limitations in bioavailability and tumor targeting, we developed an MA-loaded nucleic acid nanodrug (SNAMA). SNAMA demonstrated effective tumor growth inhibition in orthotopic and metastatic UM models through GSH-responsive release and m 6 A-mediated disulfidptosis activation. Incorporating a PD-L1 aptamer into SNAMA further improved tumor targeting and immune modulation, enhancing therapeutic efficacy. This study identifies FTO as a critical target for UM therapy and introduces SNAMA-apt as a promising nanodrug. The findings offer a foundation for m 6 A-targeted approaches in UM and other malignancies, addressing bioavailability, targeting, and immune evasion challenges.
研究领域:
肿瘤学
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分子生物学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2022
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IF 18.027
Zhijin Fan,Yichao Wang,Lanqing Li,Fanchu Zeng,Qiuping Shang,Yuhui Liao,Changhong Liang,Liming Nie
Many studies have focused on developing effective therapeutic strategies to selectively destroy primary tumors, eliminate metastatic lesions, and prevent tumor recurrence with minimal side effects on normal tissues. In this work, we synthesized engineered cellular nanovesicles (ECNVs) with tumor-homing and immune-reprogramming functions for photoacoustic (PA) imaging-guided precision chemoimmunotherapy. M1-macrophage-derived cellular nanovesicles (CNVs) were loaded with gold nanorods (GNRs), gemcitabine (GEM), CpG ODN, and PD-L1 aptamer. The good histocompatibility and tumor-homing effect of CNVs improved drug retention in the bloodstream and led to their enrichment in tumor tissues. Furthermore, the photothermal ability of GNRs enabled PA imaging-guided drug release. GEM induced tumor immunogenic cell death (ICD), and CpG ODN promoted an immune response to the antigens released by ICD, leading to long-term specific antitumor immunity. In addition, the PD-L1 aptamer relieved the inhibitory effect of the PD1/PD-L1 checkpoint on CD8+ T-cells and augmented the immunotherapeutic effect. The synergistic innate and adaptive immune responses enhanced the antitumor effect of ECNVs. In summary, this nanoplatform integrates local targeted photothermal therapy with extensive progressive chemotherapy and uses ICD to reshape the immune microenvironment for tumor ablation.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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生物医学工程
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诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Jiansen Li,Chen Cao,Xinlu Zhang,Huan Li,Qin Fan,Shutong Chen,Xu Zhang,Sheng Wang
Immune checkpoint blockade therapy has made great strides in cancer treatment, but conventional immune checkpoint blockade antibodies often lead to overactivation of the immune system and severe immune-related adverse effects. Herein, we report the design of a nanomedicine (denoted as CPD@M−TDN) based on multifunctional tetrahedral DNA nanostructures (M−TDN). In this system, a bimetallic metal–organic framework (Cu/ZIF-8) is synthesized as the core; doxorubicin-loaded polydopamine acts as a shell to reduce the immunogenicity of the nanomaterials in peripheral blood. Finally, the CpG oligodeoxynucleotides and PD-L1 aptamer-based M−TDN are coupled to the core–shell structure nanomedicine through the biotin-avidin-system. Under the acidic tumor microenvironment, the decomposition of Cu/ZIF-8 and the release of copper ions and doxorubicin can lead to immunogenic death of tumor cells through chemodynamic/chemotherapy. Furthermore, the M−TDN has the dual effects of weakening the immunosuppressive microenvironment with PD-L1 aptamer and promoting dendritic cell activation with the immunostimulant CpG. Overall, the developed CPD@M−TDN can effectively enhance the response rate to immunotherapy and has excellent potential in the field of integrated tumor treatment.
研究领域:
纳米技术
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癌症治疗
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免疫治疗
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-24
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IF 14.7
Ren Xijiao,Xue Rui,Luo Yan,Wang Shuang,Ge Xinyue,Yao Xuemei,Li Liqi,Min Junxia,Li Menghuan,Luo Zhong,Wang Fudi
Radio-immunotherapy exploits the immunostimulatory features of ionizing radiation (IR) to enhance antitumor effects and offers emerging opportunities for treating invasive tumor indications such as melanoma. However, insufficient dose deposition and immunosuppressive microenvironment (TME) of solid tumors limit its efficacy. Here we report a programmable sequential therapeutic strategy based on multifunctional fusogenic liposomes (Lip@AUR-ACP-aptPD-L1) to overcome the intrinsic radio-immunotherapeutic resistance of solid tumors. Specifically, fusogenic liposomes are loaded with gold-containing Auranofin (AUR) and inserted with multivariate-gated aptamer assemblies (ACP) and PD-L1 aptamers in the lipid membrane, potentiating melanoma-targeted AUR delivery while transferring ACP onto cell surface through selective membrane fusion. AUR amplifies IR-induced immunogenic death of melanoma cells to release antigens and damage-associated molecular patterns such as adenosine triphosphate (ATP) for triggering adaptive antitumor immunity. AUR-sensitized radiotherapy also upregulates matrix metalloproteinase-2 (MMP-2) expression that combined with released ATP to activate ACP through an “and” logic operation-like process (AND-gate), thus triggering the in-situ release of engineered cytosine-phosphate-guanine aptamer-based immunoadjuvants (eCpG) for stimulating dendritic cell-mediated T cell priming. Furthermore, AUR inhibits tumor-intrinsic vascular endothelial growth factor signaling to suppress infiltration of immunosuppressive cells for fostering an anti-tumorigenic TME. This study offers an approach for solid tumor treatment in the clinics.
研究领域:
肿瘤学
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药学
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免疫学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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