JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Can Hong,Yiming Liu,Dingwen Shi,Chao Liu,Shidong Zou,Mengqin Guo,Xingyu Chen,Chuansheng Zheng,Yanbing Zhao,Xiangliang Yang
Radiofrequency-responsive nanoparticles (RFNPs) have drawn increasingly attentions as RF energy absorbing antenna to enhance antitumor efficacy of radiofrequency ablation (RFA). However, it remains a huge challenge for inorganic RFNPs to precisely synergize RFA with other antitumor modes in a clinically acceptable way on bio-safety and bio-compatibility. In this work, RF-responsive black phosphorus (BP) nanogel (BP-Pt@PNA) was successfully fabricated by crosslinking coordination of cisplatin with BP and temperature sensitive polymer PNA. BP-Pt@PNA exhibited strong RF-heating effect and RF-induced pulsatile release of cisplatin. Under RF irradiation, BP-Pt@PNA exhibited cytotoxic enhancement on 4T1 cells. By the synergistic effect of BP and cisplatin, BP-Pt@PNA achieved RF-stimulated systemic immune effect, thus induced enhance suppression on tumor growth and metastasis. Moreover, BP-Pt@PNA realized long-term drug retention in tumor and favorable embolization to tumor-feeding arteries. With high drug loading capacity and favorable bio-safety and bio-degradability, BP-Pt@PNA is expected as an ideal RFNP for precisely synergizing RFA with other antitumor modes in clinical application.
研究领域:
纳米技术
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肿瘤学
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Haoran Wang,Honghui Liu,Yunfei Guo,Wenjing Zai,Xianghui Li,Wei Xiong,Xiaozhi Zhao,Yingfang Yao,Yiqiao Hu,Zhigang Zou,Jinhui Wu
The ideal photodynamic therapy (PDT) should effectively remove the primary tumor, and produce a stronger immune memory effect to inhibit the tumor recurrence and tumor metastasis. However, limited by the hypoxic and immunosuppressive microenvironment, the PDT efficiency is apparently low. Here, Chlorella (Chl.) is exploited to enhance local effect by producing oxygen to reverse hypoxia, and release adjuvants to reverse immunosuppressive microenvironment to enhance abscopal effect afterwards. Results from different animal models indicated that Chl. could enhance local effect and PDT related immune response. Ultimately, Chl. coupled PDT elicited anti-tumor effects toward established primary tumors (inhibition rate: 90%) and abscopal tumors (75%), controlled the challenged tumors (100%) and alleviated metastatic tumors (90%). This Chl. coupled PDT strategy can also produce a stronger anti-tumor immune memory effect. Overall, this Chl. coupled PDT strategy generates enhanced local tumor killing, boosts PDT-induced immune responses and promotes anti-tumor immune memory effect, which may be a great progress for realizing systemic effect of PDT.
研究领域:
肿瘤学
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免疫疗法
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生物技术
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微生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Ouyang Boshu,Shan Caihua,Shen Shun,Dai Xinnan,Chen Qingwang,Su Xiaomin,Cao Yongbin,Qin Xifeng,He Ying,Wang Siyu,Xu Ruizhe,Hu Ruining,Shi Leming,Lu Tun,Yang Wuli,Peng Shaojun,Zhang Jun,Wang Jianxin,Li Dongsheng,Pang Zhiqing
Due to low success rates and long cycles of traditional drug development, the clinical tendency is to apply omics techniques to reveal patient-level disease characteristics and individualized responses to treatment. However, the heterogeneous form of data and uneven distribution of targets make drug discovery and precision medicine a non-trivial task. This study takes pyroptosis therapy for triple-negative breast cancer (TNBC) as a paradigm and uses data mining of a large TNBC cohort and drug databases to establish a biofactor-regulated neural network for rapidly screening and optimizing compound pyroptosis drug pairs. Subsequently, biomimetic nanococrystals are prepared using the preferred combination of mitoxantrone and gambogic acid for rational drug delivery. The unique mechanism of obtained nanococrystals regulating pyroptosis genes through ribosomal stress and triggering pyroptosis cascade immune effects are revealed in TNBC models. In this work, a target omics-based intelligent compound drug discovery framework explores an innovative drug development paradigm, which repurposes existing drugs and enables precise treatment of refractory diseases.
研究领域:
癌症生物学
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药理学
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生物信息学
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纳米技术
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免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Jia Tan,Binbin Ding,Hao Chen,Qi Meng,Jing Li,Chunzheng Yang,Wenying Zhang,Xinyang Li,Di Han,Pan Zheng,Ping'an Ma,Jun Lin
Mesoporous silica nanoparticles (MSNs) have been widely praised as nanoadjuvants in vaccine/tumor immunotherapy thanks to their excellent biocompatibility, easy-to-modify surface, adjustable particle size, and remarkable immuno-enhancing activity. However, the application of MSNs is still greatly limited by some severe challenges including the unclear and complicated relationships of structure and immune effect. Herein, three commonly used MSNs with different skeletons including MSN with tetrasulfide bonds (TMSN), MSN containing ethoxy framework (EMSN), and pure −Si−O−Si− framework of MSN (MSN) are comprehensively compared to study the impact of chemical construction on immune effect. The results fully demonstrate that the three MSNs have great promise in improving cellular immunity for tumor immunotherapy. Moreover, the TMSN performs better than the other two MSNs in antigen loading, cellular uptake, reactive oxygen species (ROS) generation, lymph node targeting, immune activation, and therapeutic efficiency. The findings provide a new paradigm for revealing the structure-function relationship of mesoporous silica nanoadjuvants, paving the way for their future clinical application.
研究领域:
纳米技术
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免疫学
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癌症研究
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Min Zhang,Zhou Fang,Haitao Zhang,Mingxiao Cui,Mingfu Wang,Kehai Liu
In order to reverse tumor immunosuppressive microenvironment and improve antitumor immune effect based on immune checkpoint blocking, a mannose-modified liposome-based CpG ODNs and PD-L1 antagonistic peptides (P) co-delivery system (HA/M-Lipo CpG-P) was constructed, in which hyaluronic acid (HA) coating was supposed to improve the systemic circulation stability and thereby promote its accumulation in tumor tissues. When the HA/M-Lipo CpG-P complexes enter the tumor tissues, HA will be hydrolyzed under the action of hyaluronidase, exposing P peptides. Then, P peptides linked by octapeptides that can be cleaved by matrix metalloproteinases (MMPs) are released into tumor tissues under the action of MMPs, exerting a blocking effect in the PD-1/PD-L1 pathway. The M-Lipo CpG complexes can recognize macrophage surface mannose receptors through its surface modified mannose molecules, and promote the intracellular delivery of CpG ODNs, thereby activating macrophages. The results showed that HA/M-Lipo CpG-P complexes successfully reversed M2-type macrophages in tumor microenvironment (TME) to M1, thereby activating anti-tumor related immune cells and inhibiting tumor growth. Moreover, the HA/M-Lipo CpG-P complexes showed a better tumor inhibitory effect than the HA/M-Lipo CpG or the HA/M-Lipo-P (monotherapy) treatment groups. Overall, HA/M-Lipo CpG-P complexes provide a promising co-delivery strategy for targeting tumors to improve the antitumor effect based on immune checkpoint blockade.
研究领域:
肿瘤学
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免疫治疗
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药学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Zhenhua Liang,Zhenhua Yin,Xiaopeng Liu,Changyang Ma,Jinmei Wang,Yan Zhang,Wenyi Kang
A water-soluble glucomannogalactan was isolated from P . geesteranus fruit bodies by hot water extraction and column chromatography method. The structure, chain conformation and immune effect of PGP-1c (20.9 kDa) were investigated comprehensively based on high purity and neutral sugar content (94.7 ± 0.5%). Confirmed by monosaccharide composition , methylation and NMR analysis, PGP-1c was composed of unsubstituted (1,6- α -Gal and 1,6- α -3- O Me-Gal) and monosubstituted (1,2,6- α -Gal and 1,2,6- α -3- O Me-Gal) galactose units in the backbone through α -(1 → 6) glycosidic bonds and the possible branches that a long-branched chain composed of →3)-Glc-(1 → Man and a few fucoses were connected at the O -2 of galactose with a branching degree of 48%. Through the conformational behavior of the molecular chain, it was observed that PGP-1c might have a long-branched or stacked macromolecular network caused by O -CH 3 groups. Moreover, PGP-1c could promote the secretion of NO and cytokines significantly in a dose-dependent manner, which indicated a good immune-enhancing effect.
研究领域:
真菌学
·
生物化学
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Xiaoxuan Wang,Fangxuan Li,Jialu Zhang,Lu Guo,Mengmeng Shang,Xiao Sun,Shan Xiao,Dandan Shi,Dong Meng,Yading Zhao,Chao Jiang,Jie Li
PD-1/PD-L1-based immune checkpoint blockade therapy has shown limited benefits in tumor patients, partially attributed to the inadequate infiltration of immune effector cells within tumors. Here, we established a nanoplatform named DPPA/IL-15 NPs to target PD-L1 for the tumor delivery of IL-15 messenger RNA (mRNA). DPPA/IL-15 NPs were endowed with ultrasound responsiveness and contrast-enhanced ultrasound (CEUS) imaging performance. They effectively protected IL-15 mRNA from degradation and specifically transfected it into tumor cells through the utilization of ultrasound-targeted microbubble destruction (UTMD). This resulted in the activation of IL-15-related immune effector cells while blocking the PD-1/PD-L1 pathway. In addition, UTMD could generate reactive oxygen species (ROS) that induce endoplasmic reticulum (ER) stress-driven immunogenic cell death (ICD), initiating anti-tumor immunity. In vitro and in vivo studies revealed that this combination therapy could induce a robust systemic immune response and enhance anti-tumor efficacy. Thus, this combination therapy has the potential for clinical translation through enhanced immunotherapy and provides real-time ultrasound imaging guidance.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
超声成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-15
·
IF 10.2
Su Runping,Gu Jingjing,Sun Juanjuan,Zang Jie,Zhao Yuge,Zhang Tingting,Chen Yingna,Chong Gaowei,Yin Weimin,Zheng Xiao,Liu Bingbing,Huang Li,Ruan Shuangrong,Dong Haiqing,Li Yan,Li Yongyong
Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of “antigen multi-copy display” and “calcium carbonate (CaCO 3 ) biomineralization” to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO 3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4 + T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO 3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.
研究领域:
癌症免疫疗法
·
纳米技术
·
免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Yingying Zhang,Hongbin Chen,Hanjie Wang,Tiange Wang,Huizhuo Pan,Wanying Ji,Jin Chang
Immunotherapy has become a promising therapy in cancer treatment. Both photothermal therapy (PTT) and genotoxic chemotherapy can trigger immune responses. On this subject, a synergistic cancer immunotherapy nano-system was developed for treating primary and distant tumors. This long-time, synergistic therapeutic system consisted of two parts: one was indocyanine green (ICG) and sepantronium bromide (YM155) co-loaded mesoporous silica nanoparticles (MSNs) for PTT and genotoxic chemotherapy, which could effectively destroy primary tumors and thus cause exposure of tumor antigens for cancer immunotherapy. The other was silica nanoparticles (nSiO 2 ) coated with magnetic nanoparticles (MNP) and conjugated with anti-CD47 antibody (anti-CD47), which demonstrated a strong antitumor immune effect of distant tumors after PTT and genotoxic chemotherapy. In vitro and vivo results proved that this synergistic system could efficiently inhibit primary and distant tumor growth. We expected that this paper may develop a promising strategy to prevent tumor growth for basic and clinical research.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）