Small
·
2023
·
IF 13.3
Huilin Zhang,Yiwei Zhang,Haili Hu,Wenqin Yang,Xue Xia,Lei Lei,Ruyi Lin,Jiamei Li,Yuan Li,Huile Gao
Tumor vaccine is a promising cancer treatment modality, however, the convenient antigens loading in vivo and efficient delivery of vaccines to lymph nodes (LNs) still remain a formidable challenge. Herein, an in situ nanovaccine strategy targeting LNs to induce powerful antitumor immune responses by converting the primary tumor into whole-cell antigens and then delivering these antigens and nanoadjuvants simultaneously to LNs is proposed. The in situ nanovaccine is based on a hydrogel system, which loaded with doxorubicin (DOX) and nanoadjuvant CpG-P-ss-M. The gel system exhibits ROS-responsive release of DOX and CpG-P-ss-M, generating abundant in situ storage of whole-cell tumor antigens. CpG-P-ss-M adsorbs tumor antigens through the positive surface charge and achieves charge reversal, forming small-sized and negatively charged tumor vaccines in situ, which are then primed to LNs. Eventually, the tumor vaccine promotes antigens uptake by dendritic cells (DCs), maturation of DCs, and proliferation of T cells. Moreover, the vaccine combined with anti-CTLA4 antibody and losartan inhibits tumor growth by 50%, significantly increasing the percentage of splenic cytotoxic T cells (CTLs), and generating tumor-specific immune responses. Overall, the treatment effectively inhibits primary tumor growth and induces tumor-specific immune response. This study provides a scalable strategy for in situ tumor vaccination.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-19
·
IF 15.7
Zhang Lei,AL-Ammari Abdulrahman,Zhu Danxuan,Zhang Hongsong,Zhou Peng,Zhi Xu,Ding Weixiao,Li Xinmeng,Yu Qingqing,Gai Yuwen,Ma Xiaoling,Chen Chuntao,Zuo Chao,Zhang Jiaan,Zhu Wanying,Sun Dongping
Vaccines offer prophylactic treatments against atherosclerosis by eliciting effector T cell and antibody responses, which require effective delivery of antigen and adjuvant to activate dendritic cells (DC). Here we show that individual conjugation of antigen p210 and adjuvant CpG oligodeoxynucleotides onto superparamagnetic iron oxide nanoparticles formulates a nanovaccine cocktail that activates DCs for antigen cross-presentation and induction of co-stimulatory signals, cytokines and CD8 + effector/effector memory T cell responses. This nanovaccine modulates the DCs in the draining lymph nodes, activates both CD4 + and CD8 + T cells, elicits memory responses, and induces both anti-p210 IgM and IgG antibodies to suppress atherosclerosis. Lastly, three intradermal vaccinations of this nanovaccine mitigate the atherosclerosis development in the ApoE −/− mice. Our nanovaccine design and preclinical data thus presents a potential candidate for prophylactic treatment for atherosclerosis.
研究领域:
免疫学
·
心血管疾病
·
纳米医学
·
疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Jun Xu,Hui Wang,Ligeng Xu,Yu Chao,Chenya Wang,Xiao Han,Ziliang Dong,Hong Chang,Rui Peng,Yiyun Cheng,Zhuang Liu
Cancer vaccines for prevention and treatment of tumors have attracted tremendous interests as a type of cancer immunotherapy strategy. A major challenge in achieving robust T-cell responses to destruct tumor cells after vaccination is the abilities of antigen cross-presentation for antigen-presenting cells (APCs) such as dendritic cells (DCs). Herein, we demonstrate that a polyamidoamine dendrimer modified with guanidinobenzoic acid (DGBA) could serve as an effective protein carrier to enable delivery of protein antigen, thereby leading to effective antigen cross-presentation by DCs. With ovalbumin (OVA) as the model antigen and unmethylated cytosine-guanine dinucleotides (CpG) as the adjuvant, a unique type of tumor vaccine is formulated. Importantly, such DGBA-OVA-CpG nanovaccine can induce robust antigen-specific cellular immunities and further demonstrates outstanding prophylactic efficacy against B16-OVA melanoma. More significantly, the nanovaccine shows excellent therapeutic effect to treat established B16-OVA melanoma when used in combination with the programmed cell death protein 1 (PD-1) checkpoint-blockade immunotherapy. This study presents the great promises of employing rationally engineered cytosolic protein carriers for the development of tumor vaccines to achieve effective cancer immunotherapy.
研究领域:
癌症免疫学
·
纳米技术
·
疫苗学
·
肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Yingying Zhang,Tiange Wang,Yinping Zhuang,Tiandi He,Xiaoli Wu,Lin Su,Jun Kang,Jin Chang,Hanjie Wang
With the development of technology, adjuvant immunotherapy has become a promising strategy for prevention of postoperative tumor regression and metastasis by stimulating the host immune response. However, the therapeutic effects are still unsatisfactory due to the lack of synergy between different methods. In this study, an efficient synergistic immunotherapy system based on injectable sodium alginate hydrogels was designed to inhibit in situ recurrence and metastasis at the same time. On the one hand, an injectable sodium alginate (SA) hydrogel microsystem loaded with toll-like receptor (TLR) agonists (CpG ODNs) was synthesized for inhibiting in situ recurrence, and then carcinoembryonic antigen (CEA) probe was also added to detect CEA based on fluorescence resonance energy transfer (FRET) technology to monitor the occurrence and development of tumor recurrence. On the other hand, an anti-programmed cell death 1 ligand 1 antibody (anti-PD-L1)-modified SA nanogel loaded with indocyanine green (ICG@SA-anti-PD-L1 nanogel) was prepared for diagnosing and inhibiting lung metastasis by assisting orthotopic tumor therapy. In vitro and in vivo results demonstrated that this SA micro/nanosystem could monitor and inhibit postoperative recurrence and metastasis. We hope that this micro/nano-synergistic system will become an effective strategy for postoperative adjuvant immunotherapy.
研究领域:
肿瘤学
·
免疫学
·
生物材料
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Sijia Zhang,Yuanji Feng,Meng Meng,Zhen Li,Huixin Li,Lin Lin,Caina Xu,Jie Chen,Kai Hao,Zhaohui Tang,Huayu Tian,Xuesi Chen
As a representative of tumor immunotherapy, tumor vaccine can inhibit tumor growth by activating tumor-specific immune response, which has the advantages of relatively low toxicity and high efficiency, and has attracted much attention in recent years. However, there are still difficulties in how to effectively deliver tumor vaccines in vivo and make them work efficiently. It is a relatively mature method to load tumor specific antigens with suitable carriers to produce tumor vaccines. Here, a generally minimalist construction method of tumor nanovaccine was developed. A high-efficiency tumor nanovaccine (NV) was prepared in one step by a biomineralization-like method, which contained ovalbumin (OVA, model antigen), unmethylated cytosine-phosphate-guanine (CpG, adjuvant) and Mn-NP (carrier and adjuvant). NV not only showed good tumor preventive effect, but also could successfully inhibited tumor development and metastasis when combined with anti-PD-L1, and induced long-term immune memory effect. However, the method of screening tumor specific antigen to construct nanovaccine is cumbersome and tumors are heterogeneous. Therefore, surgically resected tumor tissue is the best source of antigens for preparing tumor vaccines. Next, based on the strong loading ability of the carrier, we designed a personalized tumor nanovaccine (PNV) using the supernatant of tumor abrasive fluid (STAF) as antigen based on the generally minimalist tumor nanovaccine construction strategy. PNV combined with anti-PD-L1 could successfully inhibit post-surgical tumor recurrence and induce strong and durable immune memory effects. This study presents a novel, general, and minimalist strategy to construct high-efficiency personalized nanovaccine, which has a wide range of potential applications in the field of tumor treatment.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xingyu Luo,Xiaolu Chen,Rongying Ma,Zhaoming Fu,Zuwei Liu,Qianhong Su,Huiling Fu,Yong Yang,Wei Xue
Cancer nanovaccines offer a promising strategy for fighting against tumors, however, the engineering of cancer nanovaccines that can be easily fabricated with tanglesome cancer cell-derived antigens and elicit an adequately strong tumor-specific cellular immunity remains challenging. Herein, metal-phenolic networks (MPNs) are used as an antigen delivery platform to prepare the mannose-modified MPNs nanovaccine loaded with ovalbumin (OVA) and the immunoadjuvant CpG oligodeoxynucleotide (MMOC) through the facile self-assembly. When the model antigen OVA is substituted with cancer cell membrane proteins (CCMPs), the nanovaccine is called MMCC. MMOC markedly activates dendritic cells (DCs) via the mannose-mediated endocytosis and efficiently promotes the antigen cross-presentation, thus inspiring a robust antigen-specific CD8 + T cell response as well as immune memory effect in vivo . Consequently, MMOC exhibits admirable therapeutic and preventive results on E.G7-OVA tumors. Moreover, the combination use of MMCC with anti-PD1 significantly inhibits the growth of 4T1 tumors by strengthening the cellular immunity and decreasing the proportion of regulatory T cells (Tregs). The survival rate of 4T1 tumor-bearing mice in the prophylaxis assay is maintained at 100 % by MMCC over 42 days. Altogether, this study affords a universal and effective nanovaccine preparation strategy for cancer immunotherapy and prevention.
研究领域:
癌症免疫学
·
纳米技术
·
生物医学工程
·
免疫治疗
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Shuo Liu,Xiaozhen Zhan,Zhenni Lin,Zonghua Liu,Jie Yang,Yi Zhang
In the field of anti-tumor immunotherapy, tumor vaccines gained more and more attention due to their unique advantages. The overall effectiveness of tumor vaccines is determined by the strength of the induced anti-tumor cellular immune response, which further depends on the several key steps (similar to a cascade reaction) during the whole immune response elicited by tumor vaccines. However, the design to fulfill every key step varies to a certain degree and sometimes even conflicts, usually leading to compromised vaccination effectiveness due to one or more rate-limiting steps. In this work, bacteria-like tumor vaccines with cascade reaction properties were elaborately designed to precisely aim to all the key steps of the whole immune cascade. For this purpose, the tumor vaccines were prepared by a simple layer-by-layer (LBL) self-assembly of positive-charged CpG-grafted disulfide-bond-bearing hyperbranched poly(amido amine) (HPAA-CpG) and negative charged model antigen ovalbumin (OVA) on CaCO 3 nanoparticles to form the biodegradable CaCO 3 @(OVA/HPAA-CpG) 3 vaccines. Benefiting from the cascaded properties, the vaccines could effectively load the antigen in a LBL manner, efficiently activate and enter antigen presenting cells by rational characteristics (size, morphology and PAMPs presentation), escape the lysosomes through bubbles explosive force, and approximate zero-order release the antigen into cytoplasm by virtue of LBL HPAA degradation to induce potent and continuous anti-tumor cellular immune response. The preventive and therapeutic animal tests prove the promising anti-tumor effectiveness of the vaccines. The design strategy raised in this study provides a novel view for the development of effective tumor vaccines.
研究领域:
免疫疗法
·
肿瘤疫苗
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Nano Research
·
2021
·Vol. 15
·期 2
·1183-1192
·
IF 8.897
Xu Yudi,Ma Sheng,Zhao Jiayu,Si Xinghui,Huang Zichao,Zhang Yu,Song Wantong,Tang Zhaohui,Chen Xuesi
Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death (ICD), which provides a promising alternative way for cancer immunotherapy. However, the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone. Herein, we proposed a trinity immune enhancing nanoparticles (TIENs) for boosting antitumor immune responses of chemo agents. The TIENs was constructed with Food and Drug Administration (FDA) approved polylactic acid (PLA), canonical proton-sponging cationic polymer polyethyleneimine (PEI), and Toll-like receptor 9 (TLR9) agonist cytosine phosphate guanine oligodeoxynucleotide (CpG-ODN). In in vitro studies, the TIENs was proved to (1) promote antigen capturing, (2) antigen-presenting cells (APCs) activation, and (3) antigen cross-presentation. In in vivo studies, intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models, respectively. Furthermore, after decoration with a detachable shielding, the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection. The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.
研究领域:
癌症免疫疗法
·
纳米医学
·
化疗
·
免疫学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Dandan Jiang,Tong Gao,Shuang Liang,Weiwei Mu,Shunli Fu,Yang Liu,Rui Yang,Zipeng Zhang,Yongjun Liu,Na Zhang
Lymph nodes are the main sites for immune activation and surveillance. Effective delivery of immunomodulators into lymph nodes to trigger antitumor immunity is essential for cancer treatment. Here, we propose a lymph node delivery strategy to modulate the immune response by activating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells simultaneously. Novel pH/redox dual-sensitive micelles were prepared using poly(l-histidine)-poly(ethylene glycol) (PLH-PEG) as a skeleton, which can effectively deliver immunomodulators to the lymph nodes due to their suitable particle size. At 48 h after subcutaneous injection, the accumulation efficiency in lymph nodes increased 8.12-fold compared with the control group. Subsequently, Trp2/CpG-coloaded pH/redox dual-sensitive micelles (Trp2/CpG-NPs) acted on antigen-presenting cells, fully promoting CTL activation through dendritic cell antigen cross-presentation and macrophage repolarization. IL-15-loaded pH/redox dual-sensitive micelles (IL-15-NPs) were developed to activate the killing effect of NK cells by interacting with IL-15 receptors. In the tumor-bearing mice model, this lymph node delivery strategy showed significant antitumor efficiency and the tumor inhibition rate reached 93.76%. Meanwhile, the infiltration of CTLs and NK cells in tumor tissues increased, and the immunosuppressive microenvironment was relieved by the repolarization of macrophages from M2-type to M1-type. Overall, this study highlighted the potential of the lymph node delivery strategy for cancer immunotherapy.
研究领域:
癌症免疫治疗
·
免疫学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Meng Zhang,Yingzhi Chen,Dongdong Li,Zhidi He,Hairui Wang,Aihua Wu,Weidong Fei,Caihong Zheng,Ergang Liu,Yongzhuo Huang
Cancer immunotherapy represents a medical breakthrough, but there are still many patients unable to benefit from it because of the low response rate. The immunosuppressive tumor microenvironment (TME) is the main barrier to immunotherapy. Alleviating intratumoral immunosuppression is critical for improving the immune therapeutic efficacy. This work developed an in situ vaccination strategy by using gold nanocage (AuNC)-based photothermal effect in combination with an adjuvant and PD-L1 suppressor. In specific, this therapeutic strategy included three components: AuNCs as an inducer for tumor antigen production via photothermal ablation, CpG oligodeoxynucleotides as an adjuvant to amplify immune responses, and JQ1 as a PD-L1 suppressor to inhibit an immune checkpoint. The results showed that the in situ vaccination efficiently activated dendritic cells and primed T cells and exhibited a high therapeutic efficacy in the melanoma-bearing mice. This therapeutic strategy can increase the infiltration of cytotoxic T lymphocytes, suppress the PD-L1 expression in the tumor, and repolarize tumor-associated macrophages from pro-tumor M2 to the anti-tumor M1 phenotype, thereby remodeling the TME via regulating the innate immune and adaptive immune responses.
研究领域:
癌症免疫疗法
·
纳米技术
·
生物医学工程
·
免疫学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
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
·
纳米技术
·
免疫治疗
·
生物医学工程
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2021
·
IF 5.221
Wang Weicai,Liu Xiaofan,Ding Lairong,Jin Hyung Jong,Li Xuemei
Hypoxia is not only the reason of tumor metastasis but also enhances the spread of cancer cells from the original tumor site, which results in cancer recurrence. Herein, we developed a self-assembled RNA hydrogel that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as MnO2 loaded-photodynamic agent chlorine e6 (MnO2@Ce6), and a chemotherapy drug doxorubicin (DOX) into MDA-MB-231cells. The RNA hydrogel consists of one tumour suppressor miRNA (miRNA-205) and one anti-metastatic miRNA (miRNA-182), both of which showed an outstanding effect in synergistically abrogating tumours. The hydrogel would be dissociated by endogenous Dicer enzyme to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Besides, the hydrogel as the carrier which modified aptamer to targeted MDA-MB-231 has the advantages of good biocompatibility and low cytotoxicity. This strategy could be implemented to design any other microRNA (miRNA) as the carrier, combined with other treatment methods to treat human cancer, thereby overcoming the limitations of current cancer therapies.
研究领域:
癌症生物学
·
纳米技术
·
治疗学
·
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
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