Nature Nanotechnology
·
2025
·
IF 34.9
Wu Yali,Chen Wenjuan,Deng Jingjing,Cao Xinghui,Yang Zimo,Chen Jiangbin,Tan Qi,Zhou E.,Li Minglei,Liu Jiatong,Guo Mengfei,Jin Yang
Tumour-derived microparticles (TMPs), extracellular vesicles traditionally obtained upon ultraviolet (UV) radiation of tumour cells, hold promise in tumour immunotherapies and vaccines and have demonstrated potential as drug delivery systems for tumour treatment. However, concerns remain regarding the limited efficacy and safety of UV-derived TMPs. Here we introduce a microwave (MW)-assisted method for preparing TMPs, termed MW-TMPs. Brief exposure of tumour cells to short-wavelength MW radiation promotes the release of TMPs showing superior in vivo antitumour activity and safety compared with UV-TMPs. MW-TMPs induce immunogenic cell death and reprogramme suppressive tumour immune microenvironments in different lung tumour models, enabling dual targeting of tumour cells by natural killer and T cells. We show that they can efficiently deliver methotrexate to tumours, synergistically boosting the efficacy of PD-L1 blockade. This MW-TMP development strategy is simpler, more efficient and safer than traditional UV-TMP methods.
研究领域:
肿瘤学
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免疫学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Hongxin Zhao,Fangxue Du,Jianbo Huang,Ruiqian Guo,Ziyan Feng,Ziyao Wang,Li Qiu
Sonodynamic therapy (SDT)-mediated immunogenic cell death and immune checkpoint blockade offer new opportunities for tumor treatment. However, challenges including immunosuppression, hypoxic tumor microenvironments, and inadequate drug delivery hinder therapeutic efficacy. Therefore, we developed a multifunctional biomimetic liposome microbubble named H-R@Lip@M, which is coated with melanoma cell membranes, contains perfluoropentane as its core, and is loaded with the sonosensitizer hematoporphyrin monomethyl ether and the immune adjuvant resiquimod. The targeting properties of melanoma cell membranes enable effective accumulation of nanoparticles (NPs) at tumor sites. Equipped with ultrasonic/photoacoustic imaging capabilities, these NPs allow precise control over the release of drugs and oxygen upon ultrasound stimulation. In vitro and in vivo results consistently showed that the NPs enhanced anti-tumor efficacy, halting primary tumor progression and preventing lung metastasis. Moreover, SDT increased reactive oxygen species levels within tumors, preferentially inducing apoptosis while maximizing immunogenic cell death. When combined with PD-L1 blockade, this synergy promotes dendritic cell maturation and alters various immune populations, boosting T-cell infiltration while enhancing M1 macrophage polarization and reducing regulatory T-cell presence. In summary, the proposed combination has the potential to synergistically enhance the efficacy of sono-immunotherapy by remodeling the immunosuppressive microenvironment, providing valuable insights for addressing challenges associated with SDT-based cancer therapy.
研究领域:
肿瘤学
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生物医学工程
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免疫治疗
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 12
·2844
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IF 6.525
Shuzhen Li,Wanqiong Li,Xin Yang,Yanfeng Gao,Guanyu Chen
Oral delivery is the most convenient drug administration route. However, oral delivery of peptides is extremely challenging due to the physical and chemical barriers within the gastrointestinal tract. Polysaccharides are often utilized as polymeric biomaterials in drug delivery. Among these, dietary polysaccharides extracted from okra, yam, and spirulina have been reported to stimulate innate immunity with well-known nutritional benefits. In this study, we developed a dietary-polysaccharide-modified fish-oil-based emulsion for oral co-delivery of a hydrophilic PD-L1 blocking peptide and the hydrophobic small molecule simvastatin. The optimal emulsion was nano-sized and exhibited a negative surface charge, high drug encapsulation efficiency of over 97%, low viscosity, and sustained drug release manner. The formulation could significantly increase the uptake of peptides by intestinal Caco-2 cells, which demonstrated the great potential of the formulation for promoting the oral absorption of peptides. Additionally, these dietary polysaccharides could promote dendritic cell maturation and cytokine expression in macrophages, demonstrating that these nutraceutical polysaccharides had dual roles of functioning as promising colloidal delivery systems and as potential immune modulators or adjuvants. Thus, this food-based colloidal delivery system shows promise for the oral delivery of peptide drugs and lays a great platform for future applications in immunotherapy.Keywords:dietary polysaccharide;water-in-oil-in-water emulsion;colloidal delivery system;immune modulator;PD-L1 blocking peptide;oral drug delivery
研究领域:
药剂学
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药物递送
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免疫学
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胶体科学
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产品关联
DOI
PubMed
高影响因子
Microorganisms
·
2020
·Vol. 8
·期 2
·175
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IF 4.152
Xuerun Liu,Luoyang Wang,Nan Jing,Guoqiang Jiang,Zheng Liu
Recent advances have revealed the essential role of gut microbiomes in the therapeutic efficiency of immune checkpoint inhibitors (ICIs). Inspired by biostimulation, a method using nutrients to accelerate the growth of soil microorganisms and the recovery of soil microbial consortia, here we propose a bilberry anthocyanin combo containing chitosan and low molecular citrus pectin (LCP), in which LCP–chitosan is used to encapsulate anthocyanins so to enhance its digestive stability and, moreover, modulate the microbiome more favorable for the PD-L1 blockade treatment. Using murine MC38 colon cancer as a model system, we examined the effects of the combo on modulating the gut microbiome and therapeutic efficiency of PD-L1 blockade treatment. It was shown that bilberry anthocyanins enriched the subdominant species, increased both the concentration and the proportion of butyrate in feces and enhanced intratumoral CD8+T cell infiltrations. The application of the bilberry anthocyanin combo restored the species diversity of gut microbiome decreased by LCP–chitosan and achieved the best control of tumor growth. These preliminary results indicated unprecedented opportunities of probiotics combo in improving the therapeutic efficiency of immune checkpoint inhibitor through manipulating gut microbiome.Keywords:immune checkpoint inhibitors;immunotherapy;gut microbiome;bilberry anthocyanins;low molecular citrus pectin;chitosan
研究领域:
免疫疗法
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肿瘤学
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微生物学
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营养保健品
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DOI
PubMed
高影响因子
Small
·
2023
·Vol. 19
·期 14
·2206174
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IF 13.3
Chen Cheng,Weixi Jiang,Yuanli Luo,Li Wan,Xun Guo,Zhuoyan Xie,Rui Tang,Tong Huang,Jingxue Wang,Chier Du,Zhigang Wang,Haitao Ran,Pan Li,Zhiyi Zhou,Jianli Ren
Multidrug resistance (MDR) and metastasis in cancer have become increasingly serious problems since antitumor efficiency is greatly restricted by a single therapeutic modality and the insensitive tumor microenvironment (TME). Herein, metal–phenolic network-functionalized nanoparticles (t-P@TFP NPs) are designed to realize multiple therapeutic modalities and reshape the TME from insensitive to sensitive under multimodal imaging monitoring. After a single irradiation, a near-infrared laser-activated multistage reaction occurs. t-P@TFP NPs trigger the phase transition of perfluoropentane (PFP) to release tannic acid (TA)/ferric ion (Fe 3+ )-coated paclitaxel (PTX) and cause hyperthermia in the tumor region to efficiently kill cancer cells. Additionally, PTX is released after the disassembly of the TA-Fe 3+ film by the abundant adenosine triphosphate (ATP) in the malignant tumor, which concurrently inhibits ATP-dependent drug efflux to improve sensitivity to chemotherapeutic agents. Furthermore, hyperthermia-induced immunogenic cell death (ICD) transforms “cold” tumors into “hot” tumors with the assistance of PD-1/PD-L1 blockade to evoke antitumor immunogenicity. This work carefully reveals the mechanisms underlying the abilities of these multifunctional NPs, providing new insights into combating the proliferation and metastasis of multidrug-resistant tumors.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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药学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-17
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IF 17.694
Guan Xin,Sun Liping,Shen Yuting,Jin Fengshan,Bo Xiaowan,Zhu Chunyan,Han Xiaoxia,Li Xiaolong,Chen Yu,Xu Huixiong,Yue Wenwen
Cancer recurrence after surgical resection (SR) is a considerable challenge, and the biological effect of SR on the tumor microenvironment (TME) that is pivotal in determining postsurgical treatment efficacy remains poorly understood. Here, with an experimental model, we demonstrate that the genomic landscape shaped by SR creates an immunosuppressive milieu characterized by hypoxia and high-influx of myeloid cells, fostering cancer progression and hindering PD-L1 blockade therapy. To address this issue, we engineer a radio-immunostimulant nanomedicine (IPI549@HMP) capable of targeting myeloid cells, and catalyzing endogenous H 2 O 2 into O 2 to achieve hypoxia-relieved radiotherapy (RT). The enhanced RT-mediated immunogenic effect results in postsurgical TME reprogramming and increased susceptibility to anti-PD-L1 therapy, which can suppress/eradicate locally residual and distant tumors, and elicits strong immune memory effects to resist tumor rechallenge. Our radioimmunotherapy points to a simple and effective therapeutic intervention against postsurgical cancer recurrence and metastasis.
研究领域:
肿瘤学
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免疫疗法
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纳米技术
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放射肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-23
·
IF 10.435
Jiang Weixi,Su Lei,Ao Meng,Guo Xun,Cheng Chen,Luo Yuanli,Xie Zhuoyan,Wang Xingyue,Wang Junrui,Liu Shuling,Cao Yang,Li Pan,Wang Zhigang,Ran Haitao,Zhou Zhiyi,Ren Jianli
Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract
研究领域:
癌症治疗
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纳米技术
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药学
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免疫疗法
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Yinghao Ding,Xueying Zhu,Jian Wen,Junchao Xiong,Shengyi Zhang,Zhimou Yang,Zhi-Wen Hu
Antigen presentation deficiency restricted by class I major histocompatibility complex (MHC-I) causes low antigenicity and antigen escape in tumors, thereby limiting T-cell immunotherapy outcomes. Here, a combined tumor immunotherapy is developed, in which tumors can present exogenous non-tumor antigens, and adoptively transferred CD8 + T cells specific for these antigens are re-targeted to attack tumors. The approach leverages a cascade-responsive peptide self-assembly to co-deliver suitable antigens and the chemotherapeutic drug camptothecin (CPT) to tumors. As a proof-of-concept, to re-target ovalbumin (OVA)-specific OT-I CD8 + T cells against tumors, PSA (Nap-GFFpYE-ss-Ag) and CPSA (CPT-GFFpYE-ss-Ag) are constructed, containing an OVA-derived epitope OVA 257-264 and/or CPT. The design enables the release of a unique N-terminal extended OVA 257-264 and CPT into the cytosol. As a result, the extended antigen is efficiently presented on the tumor surface by MHC-I, and CPT further enhances this presentation. When combined with adoptively transferred OT-I CD8 + T cells, the approach effectively facilitates CD8 + T cell infiltration and tumor inhibition. Additionally, CPSA treatment sensitizes immune responses to programmed cell death-ligand 1 (PD-L1) blockade, allowing the approach to synergize with an anti-PD-L1 antibody for improved tumor eradication.
研究领域:
肿瘤免疫学
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纳米医学
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药物递送系统
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免疫治疗
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分子自组装
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Rongrong Zheng,Ni Yang,Qiuyuan Li,Zuxiao Chen,Chuyu Huang,Linping Zhao,Xin Chen,Shiying Li
The combination of therapy-induced immunogenic cell death (ICD) and immune checkpoint blockade can provide a mutually reinforced strategy to reverse the poor immunogenicity and immune escape behavior of tumors. In this work, a chimeric peptide-engineered immunostimulant (ER-PPB) is fabricated for endoplasmic reticulum (ER)-targeted photodynamic immunotherapy against metastatic tumors. Among which, the amphiphilic chimeric peptide (ER-PP) is composed of ER-targeting peptide FFKDEL, hydrophilic PEG 8 linker and photosensitizer protoporphyrin IX (PpIX), which could be assembled with a PD-1/PD-L1 blocker (BMS-1) to prepare ER-PPB. After passively targeting at tumor tissues, ER-PPB will selectively accumulate in the ER. Next, the localized PDT of ER-PPB will produce a lot of ROS to destroy the primary tumor cells, while increasing the ER stress to initiate a robust ICD cascade. Moreover, the concomitant delivery of BMS-1 can impede the immune escape of tumor cells through PD-1/PD-L1 blockade, thus synergistically activating the immune system to combat metastatic tumors. In vitro and in vivo results demonstrate the robust immune activation and metastatic tumor inhibition characteristics of ER-PPB, which may offer a promising strategy for spatiotemporally controlled metastatic tumor therapy.
研究领域:
癌症研究
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免疫疗法
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药学
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yu Tian,Hongshu Jing,Quan Wang,Suxian Hu,Zhihua Wu,Yourong Duan
Immune checkpoint blockade, especially the programmed cell death ligand 1 (PD-L1) blockade, has revolutionized the treatment of melanoma . However, PD-1/PD-L1 monotherapy leads to unsatisfactory therapeutic outcomes. The immunotherapy of melanoma could be improved by adding doxorubicin (DOX), which triggers immunogenic cell death (ICD) effect to activate anti-tumor immunity. Additionally, microneedles, especially dissolving microneedles (dMNs), can further enhance outcomes of chemo-immunotherapy due to the physical adjuvant effect of dMNs. Herein, we developed the dMNs-based programmed delivery system that incorporated pH-sensitive and melanoma-targeting liposomes to co-deliver DOX and siPD-L1, achieving enhanced chemo-immunotherapy of melanoma (si/ [email protected] dMNs). The incorporated si/ [email protected] LPs demonstrated uniform particle size, pH-sensitive drug release, high in vitro cytotoxicity and targeting ability. Besides, si/ [email protected] LPs effectively downregulated the expression of PD-L1, induced tumor cell apoptosis and triggered ICD effect. The si/ [email protected] LPs also showed deep penetration (approximately 80 μm) in 3D tumor spheroids. Moreover, si/ [email protected] dMNs dissolved rapidly into the skin and had sufficient mechanical strength to penetrate skin, reaching a depth of approximately 260 μm in mice skin. In mice model of melanoma tumor, si/ [email protected] dMNs exhibited better anti-tumor efficacy than monotherapy by dMNs and tail intravenous injection at the same dose. This was due to the higher cytotoxic CD8 + T cells and the secreted cytotoxic cytokine IFN-γ evoked by si/ [email protected] dMNs, thereby eliciting strong T-cell mediated immune response and resulted in enhanced anti-tumor effects. In conclusion, these findings suggested that si/ [email protected] dMNs provided a promising and effective strategy for enhanced chemo-immunotherapy of melanoma.
研究领域:
肿瘤学
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药学
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免疫学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Shizhen Geng,Pengke Guo,Xinling Li,Yaru Shi,Jing Wang,Mengnian Cao,Yunya Zhang,Kaixiang Zhang,Airong Li,Haiwei Song,Zhenzhong Zhang,Jinjin Shi,Junjie Liu,Yiling Yang
Immune checkpoint blockade (ICB) therapy has been approved for breast cancer (BC), but clinical response rates are limited. Recent studies have shown that commensal microbes colonize a variety of tumors and are closely related to the host immune system response. Here, we demonstrated that Fusobacterium nucleatum (F.n), which is prevalent in BC, creates an immunosuppressive tumor microenvironment (ITME) characterized by a high-influx of myeloid cells that hinders ICB therapy. Administering the antibiotic metronidazole in BC can deplete F.n and remodel the ITME. To prevent an imbalance in the systemic microbiota caused by antibiotic administration, we designed a biomimetic nanovehicle for on-site antibiotic delivery inspired by F.n homing to BC. Additionally, ferritin-nanocaged doxorubicin was coloaded into this nanovehicle, as immunogenic chemotherapy has shown potential for synergy with ICB. It has been demonstrated that this biomimetic nanovehicle can be precisely homed to BC and efficiently eliminate intratumoral F.n without disrupting the diversity and abundance of systemic microbiota. This ultimately remodels the ITME, improving the therapeutic efficacy of the PD-L1 blocker with a tumor inhibition rate of over 90% and significantly extending the median survival of 4T1 tumor-bearing mice.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Yunjian Yu,Jie Li,Boyi Song,Zhuang Ma,Yufei Zhang,Haonan Sun,Xiaosong Wei,Yayun Bai,Xueguang Lu,Peng Zhang,Xinge Zhang
Checkpoint inhibitors, such as antibodies blocking the PD-1/PD-L1 pathway, are among the most promising immunotherapies to treat metastatic cancers, but their response rate remains low. In addition, the usage of monoclonal antibodies as checkpoint inhibitors is associated with a series of drawbacks. Herein, an all synthetic nanoparticle with PD-L1 blockade capability is developed for cancer photothermal-immunotherapy. The polymeric nanoparticle integrates photothermal treatment, antitumor vaccination, and PD-1/PD-L1 blockade in a single system to augment the antitumor efficacy. In a CT26 bilateral tumor model, intravenously injected nanoparticles accumulate in tumor sites and mediate strong photothermal effects, eradicate the NIR treated primary tumors and elicit strong antitumor immunity by inducing immunogenic cell death (ICD). Growth of the untreated distant tumors is also suppressed due to the synergies of systemic antitumor immune activation and PD-L1 blockade. Our strategy offers a simple but promising approach for the treatment of metastatic cancer.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
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）