ACS Applied Bio Materials
·
2021
·
IF 0
Yue Duan,Han Yang,Junxiao Gao,Daohe Wei,Yue Zhang,Jian Wang,Xinhui Zhang,Jinchao Zhang,Kun Ge,Xiaoli Wu,Jin Chang
Immunotherapy has shown great potential in cancer therapeutics but has limitations of the insufficient activation of dendritic cells (DCs) and immune-suppressive microenvironment. To overcome these obstacles, a cascade synergistic immunotherapy nanosystem (denoted as CpG@PDA-FA) was designed to elevate anticancer immune response. The combination nanosystem including a photothermal agent polydopamine (PDA) and immunomodulator CpG oligodeoxynucleotides (CpG ODNs). On the one hand, polydopamine (PDA) acts as a photothermal agent to induce low-temperature PTT. It leads to immunogenic cell death (ICD), a programmed cell death pathway, which can activate DCs and enhance the antitumor immune response of T cells. On the other hand, CpG ODNs further promote maturation and migration of DCs as well as ameliorates the immunosuppression microenvironment of the tumor (TME). This paper focuses on a cancer synergistic treatment of ICD-induced immunotherapy by low-temperature PTT and ameliorates TME by immunomodulator CpG ODNs. We proved that CpG@PDA-FA NPs realized a remarkable synergistic treatment effect compared with respective single PTT or CpG therapy in the maturation of DCs and activation of T cells. In addition, CpG@PDA-FA NPs also reduced myeloid-derived suppressor cells and regulatory T cells to relieve immunosuppression. Hence, CpG@PDA-FA NPs provide a bidirectional immunotherapy strategy for tumor inhibition and highlight the cascade effects of low-temperature PTT and immunotherapy.
研究领域:
肿瘤学
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免疫治疗
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纳米技术
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 18
·3491-3500
·
IF 7.571
Xiao He,Yannv Qu,Xiaohong Lin,Jiapan Sun,Zhiru Jiang,Chaodong Wang,Yuanfei Deng,Fei Yan,Yansun Sun
Self-assembled amino acid derivatives could form well-defined nanostructures which have great application value for drug delivery systems. In particular, D-amino acid derivatives possess tremendous advantages including anti-degradation and good lysosome escape compared with L-amino acid derivatives. In this work, 9-fluorenylmethyloxycarbonyl (Fmoc) neighboring D-arginine derivatives were replaced by dibenzocyclooctyne (DBCO) to extend the class of functional D-arginine derivatives, which were further reacted with various cross-linkers including azide to construct a library of self-assembled supramolecular nanovehicles and strengthen the stability of nanostructures for disease immunotherapy. Moreover, in vitro studies demonstrated that the combination of DBCO modified D-arginine derivative DR3 and cross-linker C1 not only reinforced the cellular uptake efficiency of ovalbumin (OVA) which was chosen as the model antigen, but also promoted the cytokine TNF-α release of RAW 264.7 cells after the introduction of adjuvant unmethylated cytosine-phosphate-guanine dinucleotides (CpG). Furthermore, the nanovaccine based on DR3C1 could enhance the antigen OVA and adjuvant cytosolic delivery of marrow derived dendritic cells (BMDCs), which improved the antigen-presentation cross efficiency and induced the maturation of BMDCs. Taken together, we believe that D-arginine derivatives functionalized by DBCO provide an effective strategy for disease immunotherapy and act as a great potential delivery tool.
研究领域:
纳米技术
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免疫学
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药物递送系统
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生物材料
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
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
Advanced Science
·
2024
·
IF 14.3
Mengmeng Xiong,Ying Zhang,Huan Zhang,Qiaoqiao Shao,Qifan Hu,Junjie Ma,Yiqun Wan,Lan Guo,Xin Wan,Haitao Sun,Zhongyi Yuan,Hao Wan
Aggressive nature of colon cancer and current imprecise therapeutic scenarios simulate the development of precise and effective treatment strategies. To achieve this, a tumor environment-activated photosensitized biomimetic nanoplatform (PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM) is fabricated by encapsulating metal-organic framework loaded with developed photosensitizer PEG 2000 -SiNcTI-Ph and immunoadjuvant CpG oligodeoxynucleotide within fusion cell membrane expressing programmed death protein 1 (PD-1) and cluster of differentiation 47 (CD47). By stumbling across, systematic evaluation, and deciphering with quantum chemical calculations, a unique attribute of tumor environment (low pH plus high concentrations of adenosine 5′-triphosphate (ATP))-activated photodynamic effect sensitized by long-wavelength photons is validated for PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM, advancing the precision of cancer therapy. Moreover, PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM evades immune surveillance to target CT26 colon tumors in mice mediated by CD47/signal regulatory proteins α (SIRPα) interaction and PD-1/programmed death ligand 1 (PD-L1) interaction, respectively. Tumor environment-activated photodynamic therapy realized by PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM induces immunogenic cell death (ICD) to elicit anti-tumor immune response, which is empowered by enhanced dendritic cells (DC) uptake of CpG and PD-L1 blockade contributed by the nanoplatform. The photodynamic immunotherapy efficiently combats primary and distant CT26 tumors, and additionally generates immune memory to inhibit tumor recurrence and metastasis. The nanoplatform developed here provides insights for the development of precise cancer therapeutic strategies.
研究领域:
肿瘤学
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生物医学工程
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纳米技术
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免疫学
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化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2022
·Vol. 15
·期 9
·8326-8335
·
IF 10.269
Li Xiangxia,Chen Guiyuan,Wang Yangyi,Su Lanhong,Chen Bo,Wu Kecheng,Xing Yun,Song Zechenxi,Dai Ruike,Liu Tianxin,Zhao Jiaao,Xie Zhe,Zhou Peijie,Xia Xiaoping,Min Yuanzeng
In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNs@Lipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy.
研究领域:
免疫学
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纳米医学
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肿瘤学
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药学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2018
·Vol. 9
·期 1
·1-14
·
IF 12.353
Liang Huiyi,Peng Bo,Dong Cong,Liu Lixin,Mao Jiaji,Wei Song,Wang Xinlu,Xu Hanshi,Shen Jun,Mao Hai-Quan,Gao Xiaohu,Leong Kam W.,Chen Yongming
Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage. This culminates in the manifestation of partial mobility recovery of the treated rats in a rotational cage test. Mechanistic studies on intracellular trafficking and biodistribution of cNP, as well as measurement of cytokine expression in the joints and cfDNA levels in systemic circulation and inflamed joints also correlate with therapeutic outcomes. This work suggests a new direction of nanomedicine in treating inflammatory diseases.
研究领域:
纳米医学
·
炎症性疾病
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风湿病学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Yang Sui,Ji Li,Jiqiang Qu,Ting Fang,Hongyan Zhang,Jian Zhang,Zheran Wang,Mingyu Xia,Yinghui Dai,Dongkai Wang
Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years. A major challenge of cancer vaccine is to target cytosols of dendritic cells (DCs) in the lymph nodes (LNs) to enhance efficiency of antigen cross-presentation, which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells. Here, we address this issue by conjugating ovalbumin (OVA) to PEG-PCL using disulfide bond (-ss-), and the degradable pH-responsive polymer-PEI-PCL as delivery carrier. In addition, the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs. Subsequently, CpG ODN 1826 , a TLR-9 agonist, was further introduced into a mixed micelle of 30 nm or less as a unique tumor vaccine. Importantly, the results demonstrated the mixed micelles with 1:1 mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs, meanwhile, OVA was modified to the surface of mixed micelles via disulfide bonds (-ss-) for promotion efficiency of antigen cross-presentation. More surprisingly, combination of tumor vaccine with anti-PD-1, the therapy of ectopic melanoma (B16-OVA) and lung metastasis melanoma (B16-OVA) is excellent therapeutic effect. Taken together, our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.
研究领域:
癌症免疫学
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纳米技术
·
药物递送系统
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 21
·2101199
·
IF 9.933
Haihui Wang,Yongfei Liu,Xiaohui Zhu,Chengyun Chen,Zhangcheng Fu,Min Wang,Danying Lin,Zhaowei Chen,Chunhua Lu,Huanghao Yang
Combinatorial CpG oligonucleotide (CPG) and chemotherapy drug represent a promising approach to reactivate immune system. However, these two agents possess different physicochemical properties, hindering the application of direct self-assembly of these two cargos into a single nanostructure. Here, a multistage cooperative nanodrug is developed by the direct self-assembly of cis-platinum (CDDP, Pt), l -arginine ( l -Arg, R), and CPG (defined as PtR/CPG) for antitumor chemoimmunotherapy. First, the CDDP can induce cell apoptosis. Meanwhile, CDDP also promotes the production of H 2 O 2 , catalyzing the conversion of l -Arg into nitric oxide (NO). The generated NO decreases the multidrug resistance of cells toward CDDP. Thus, the synergistic effects of CDDP and NO can trigger immunogenic cell death to produce tumor-associated antigens (TAAs). The TAAs and CPG will induce the maturation of dendritic cells (DCs) and enhance antigen presentation ability of DCs. In this way, the PtR/CPG can reverse the immunosuppressive microenvironment, sensitizing tumors to immune checkpoint inhibitors mediated by the programmed death-ligand 1 (PD-L1) antibody. Furthermore, the PtR/CPG combined with the PD-L1 antibody decreases the exhaustion and dysfunction of cytotoxic T lymphocytes to elicit durable systemic immune response. As a result, the prepared PtR/CPG nanodrug in combination with PD-L1 may be highly significant for cancer immunotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
药学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Yizhong Peng,Xuanzuo Chen,Zilong Rao,Wei Wu,Huiyin Zuo,Kaibin Chen,Kanglu Li,Hui Lin,Sheng Liu,Yan Xiao,BaiChuan Wang,Daping Quan,Xiangcheng Qing,Ying Bai,Zengwu Shao
Chronic low back pain mainly attributed to intervertebral disc (IVD) degeneration. Endogenous damage-associated molecular patterns (DAMPs) in the injured IVD, particularly mitochondria-derived nucleic acid molecules (CpG DNA), play a primary role in the inflammatory responses in macrophages. M1-type macrophages form a chronic inflammatory microenvironment by releasing pro-inflammatory factors and nerve growth factor (NGF) that induce nerve growth into the inner annulus fibrosus, resulting in persistent hyperalgesia. We fabricated an amphiphilic polycarbonate that naturally forms cationic nanoparticles (cNP) in aqueous solutions, with the hydrophobic core loaded with TrkA-IN-1, an antagonist against the NGF receptor (TrkA). The drug delivery nanoparticles were denoted as TI-cNP. TrkA-IN-1 and TI-cNP were added to the decellularized annulus fibrosus matrix (DAF) hydrogel to form hybrid hydrogels, denoted as TI-DAF and TI-cNP-DAF, respectively. As a result, TrkA-IN-1 showed a delayed release profile both in TI-DAF and TI-cNP-DAF. Each mole of cNP could bind approximately 3 mol of CpG DNA to inhibit inflammation. cNP-DAF and TI-cNP-DAF significantly inhibited the M1 phenotype induced by CpG DNA. TI-DAF and TI-cNP-DAF reduced neurite branching and axon length, and inhibited the expression of neurogenic mediators (CGRP and substance P) in the presence of NGF. Besides, TI-cNP-DAF relieved mechanical hyperalgesia, reduced CGRP and substance P expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat disc herniation model. Summarily, TI-cNP-DAF, a novel composite IVD hydrogel, efficiently mediated the inflammatory environment, inhibited nerve ingrowth and sensitization, and could be clinically applied for treating discogenic pain. Statement of Significance : Discogenic lower back pain, related to intervertebral disc degeneration (IDD), imposes a tremendous health and economic burden globally. M1-type macrophages release pro-inflammatory factors and nerve growth factor (NGF) that induce nerve growth into the inner annulus fibrosus, resulting in persistent hyperalgesia and discogenic pain. Reconstructing matrix integrity and modulating the inflammatory microenvironment are promising strategies for preventing the ingrowth and activation of neurites. The TI-cNP-DAF hydrogel recovers tissue integrity, alleviates inflammation, and delivers the TrkA antagonist to inhibit the activity of NGF, thus restraining hyperinnervation and nociceptive input. Due to its simple production process, injectability, and acellular strategy, the hydrogel is operable and holds great potential for treating discogenic lower back pain.
研究领域:
生物医学工程
·
神经科学
·
疼痛管理
·
组织工程
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2022
·Vol. 16
·期 5
·7148-7163
·
IF 10.269
Zhang Xiaoge,Chen Xiaomei,Zhang Peng,Li Meiting,Feng Miao,Zhang Yaqian,Cheng Lili,Tang Junjie,Xu Langtao,Liu Yadong,Liu Zhuoyin,Cao Zhong,Liu Jie
Nanomaterial-mediated phototherapy in tumor treatment has been developed rapidly in the past few years due to its noninvasive character. However, the low energy conversion efficiency and high recombination rate of the photo-triggered electron-hole pairs of single nano-agent limit the phototherapy efficiency. Herein, we constructed a novel two-dimensional nanoheterojunction MoS 2 -Ti 3 C 2 (MT), which allowed a high photothermal conversion efficiency (59.1%) as well as an effective separation of photo-triggered electron-hole pairs for reactive oxygen species (ROS) generation under single 808 nm laser irradiation. Upon the modification of the mitochondrial targeted molecule (3-proxycarboxylic) triphenyl phosphine bromide (TPP) and 4T1 cell membrane, m@MoS 2 -Ti 3 C 2 /TPP (m@MTT) could effectively target to the tumor cell and further locate to the mitochondria to amplify tumor-specific oxidative stress, which not merely effectively inhibits the local tumor growth but also induces tumor immunogenic cell death (ICD) for activating antitumor immune response. Additionally, cytosine guanine dinucleotide (CPG), as a Toll-like receptor 9 (TLR9) agonist, was further introduced to the system to boost adaptive immune responses, resulting in improved level of cytotoxic T cells as well as a decrease in the number of regulatory T cells. In vivo antitumor mechanism studies demonstrated that not only the primary and distant tumors in 4T1 bearing-tumor mice model were significantly inhibited, but also the lung metastasis of tumor was effectively suppressed. Therefore, this work revealed the ROS generation mechanism of MT nanoheterojunction and provided a novel strategy to fabricate a biomedically applicable MT nanoheterojunction for tumor treatment.
研究领域:
纳米技术
·
癌症治疗
·
光疗
·
免疫疗法
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
BMC Medicine
·
2022
·Vol. 20
·期 1
·1-18
·
IF 11.15
Cheng Yibin,Wang Caixia,Wang Huihui,Zhang Zhiwei,Yang Xiaopeng,Dong Yanming,Ma Lixin,Luo Jingwen
Background The application of combination therapy for cancer treatment is limited due to poor tumor-specific drug delivery and the abscopal effect. Methods Here, PD-L1- and CD44-responsive multifunctional nanoparticles were developed using a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody). Results PEI-OA greatly improved the drug loading capacity and encapsulation efficiency of the nanoplatform, while the anti-PD-L1 antibody significantly increased its cellular uptake compared to other treatment formulations. Pharmacodynamic experiments confirmed that the anti-PD-L1 antibody can strongly inhibit primary breast cancer and increase levels of CD4+ and CD8+ T cell at the tumor site. In addition, chloroquine reversed the “immune-cold” environment and improved the anti-tumor effect of both chemotherapeutics and immune checkpoint inhibitors, while it induced strong immune memory and prevented lung metastasis. Conclusions Our strategy serves as a promising approach to the rational design of nanodelivery systems for simultaneous active targeting, autophagy inhibition, and chemotherapy that can be combined with immune-checkpoint inhibitors for enhanced breast cancer treatment.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Hongping Wan,Kai Deng,Zhengqun Huang,Yunhan Yang,Bo Jing,Yumei Feng,Yuanfeng Li,Yong Liu,Mingqin Lu,Xinghong Zhao
Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan–catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions. Ssp-Chic-RBD-CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92-fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C-C motif) ligand 20 (CCL20)-driven DCs recruitment and maturation by Ssp-Chic-RBD-CpG are evidenced by a cell co-culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF-κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein-based subunit vaccines as well when intranasal administration is needed.
研究领域:
纳米技术
·
免疫学
·
疫苗开发
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）