JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Mengyue Li,Hanxi Zhang,Peizheng Xiong,Yuhan He,Wanyi Zhou,Chunhui Wu,Xiaoling Liao,Wei Zhang,Hong Yang,Yiyao Liu
Developing effective nanoplatforms for chemo-immunotherapy to achieve enhanced tumor suppression and systemic antitumor immunity has recently received extensive attention. Herein, we formulated a multifunctional DNA sandwich nanodevice, DSWAC/siPD-L1, based on triangular DNA origami, to implement enhanced cancer chemo-immunotherapy. Taking advantage of the tumor-targeting ability of the AS1411 aptamer, DSWAC/siPD-L1 efficiently delivered doxorubicin (DOX), CpG, and siPD-L1 into tumor cells. Moreover, the sandwich cavity spatially protects siPD-L1 from degradation, and the featured design of the DNA/RNA duplex linkers ensures effective intracellular release of siPD-L1. The pH-responsive release of cytotoxic DOX induces apoptosis and initial mild immunogenic cell death of tumor cells, presenting antigens to enhance the maturation of dendritic cells (DCs) with the assistance of the immune adjuvant CpG, thereby activating cytotoxic T lymphocytes to amplify antitumor immunity. Simultaneously, siPD-L1 downregulated the endogenous expression of PD-L1 to inhibit adaptive tumor immune escape. DSWAC/siPD-L1 initiated the iterative revolution of the cancer-immunity cycle, leading to the inhibition of primary and metastatic tumors, as demonstrated by DC maturation and T-cell infiltration in established subcutaneous primary tumor model and metastatic lung tumor model. Furthermore, the superior antitumor effect of DSWAC/siPD-L1 resulted in approximately 91 % inhibition of primary tumor growth and 93 % prevention of lung metastasis. Collectively, this study describes a siPD-L1-based sandwich DNA nanodevice functionalized with AS1411/CpG for enhanced cancer chemo-immunotherapy, inspiring the creation of more innovative drug nanocarriers and the exploitation of novel cancer therapies.
研究领域:
纳米医学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Fengyi Du,Lixia Xu,Haoran Wang,Mengke Lu,Qinxin Wang,Xiaonan Qiu,Baoding Chen,Miaomiao Zhang
Photothermal therapy-triggered whole-tumor cell antigens release has revolutionized in situ cancer vaccine, but insufficient anticancer immunity cycle activation greatly limits its curative effect. Herein, we designed an NIR-triggered cascading in situ vaccine (FCDs-A/C@HGs) by incorporating the Fe-doped carbon dots (FCDs), azo-initiator (AIPH), and immune adjuvant (cyclophosphamide) into the thermosensitive hydrogel. Due to iron doping, the as-prepared FCDs exhibited high photothermal conversion performance and favorable MR imaging capability. Upon intratumoral injection, local hyperthermia mediated by FCDs-A/C@HGs and the subsequent generation of alkyl radicals from AIPH synergistically induced immunogenic cell death in tumor cells. Remarkably, the FCDs-A/C@HGs elicited strong anticancer immune activation by inhibiting regulatory T cells and promoting dendritic cell maturation, thereby enhancing differentiation of cytotoxic CD8+ T cells and memory T cells. This study presents an effective therapeutic platform for in situ tumor suppression and sustained activation of the anticancer immunity cycle.
研究领域:
生物医学工程
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肿瘤免疫学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-20
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IF 12.6
Sui Dezhi,Song Yanzhi,Deng Yihui
Neutrophils play a critical role in the cancer-immunity cycle and are associated with poor clinical outcomes. Recent research has primarily focused on the targeted delivery, phenotypic reversal, and reprogramming of tumor-associated neutrophils, while the impact of disease-associated neutrophils (DANs) on antitumor therapy remains understudied. Since liposomes, as drug delivery carriers, possess excellent biocompatibility and stability, making them particularly suitable for combination therapy, we optimized the formulation of asymmetrically branched polyethylene glycol-modified mitomycin C lipid prodrug liposomes (PEG2,5 K@MLP-L) and prepared hyaluronic acid and sialic acid ester stearate-co-modified dexamethasone palmitate liposomes (HA*SAS@DXP-L) to study DANs in normal, obese, aged, and septic mice. An increase in mitochondria and lysosomes in Ly-6G+CXCR2high DANs accelerated drug clearance, reduced CD3+CD8+ T cell activity in tumor-draining lymph nodes, and decreased CD8+ T cell infiltration in tumors. As the proportion of DANs increased, the efficacy of PEG2,5 K@MLP-L decreased. Combination therapy with PEG2,5 K@MLP-L and HA*SAS@DXP-L can reshape DANs, promote the cancer-immunity cycle, and enhance treatment efficacy. This study identifies key characteristics and functions of DANs and presents a promising strategy for improving clinical outcomes.Graphical
研究领域:
肿瘤学
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免疫学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2024
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IF 12.4
Nan Gao,Yiran Huang,Shisuo Jing,Meng Zhang,Ergang Liu,Lu Qiu,Jing Huang,Bahtiyor Muhitdinov,Yongzhuo Huang
Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn 2+ ), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn 2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn 2+ -pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn 2+ -pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro : promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn 2+ -embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.
研究领域:
癌症免疫治疗
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材料科学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2018
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IF 3.466
Xian Tang,Jingdong Rao,Sheng Yin,Jiaojie Wei,Chunyu Xia,Man Li,Ling Mei,Zhirong Zhang,Qin He
The Cancer-Immunity Cycle is a series of anticancer immune responses initiated and allowed to proceed and expand iteratively. Paclitaxel (PTX) is a classic chemotherapeutic agent, which could induce immunogenic cell death (ICD) to trigger the Cancer-Immunity Cycle. However, the Cycle is severely impaired by tumor cell immunosuppression of host T cell antitumor activity through the programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) (PD-1/PD-L1) immune checkpoint pathway. Here, we demonstrated that PTX mediated the Cancer-Immunity Cycle could be enhanced by PD-L1 knockdown (KD) and followed mTOR pathway inhibition in tumor cells. PD-L1 siRNA (siP) and the hydrophobic chemotherapy drug PTX were co-delivered with a rationally designed hybrid micelle (HM). We showed clear evidence that the HM-siP/PTX is capable of delivering siP and PTX simultaneously to the B16F10 cells both in vitro and in vivo . We demonstrated that HM-PTX/siP reduced the expression of PD-L1 and p-S6K (a marker of mTOR pathway activation) both in vitro and in melanoma-bearing mice and attenuated synergistically tumor growth by chemical toxicity , promoting cytotoxic T-cell immunity and suppressing the mTOR pathway.
研究领域:
肿瘤学
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免疫治疗
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2022
·
IF 15.304
Jun Dai,Xiaoqi Dong,Rui Liu,Biao Chen,Xiyuan Dong,Quan Wang,Jing-Jing Hu,Fan Xia,Xiaoding Lou
Immunotherapy maintains the cancer-immunity cycle via re-activating the immune system, so as to achieve the purpose of anti-tumor. However, the response rate of current tumor immunotherapy strategies is still low. Even the most reported immune checkpoint block (ICB), the objective response rate (ORR) is only about 10–30%. Here, aiming at obtaining a higher response rate, we designed a cascade amplification nanocomposite consisting of the immune adjuvant polyinosinic:polycytidylic acid [Poly (I:C)] and aggregation-induced emission luminogen (AIEgen)-modified modular peptide (named PMRA). The PMRA includes: D PPA-1 peptide (P), an immune checkpoint inhibitor; PLGLAG peptide (M), a matrix metalloproteinase 2 (MMP-2) responsive sequence to promote the release of D PPA-1; RRRRRRRR peptide (R), for loading the Poly (I:C); PyTPA (A), a photosensitizer with AIE property. In cancer-immunity cycle, photodynamic therapy (PDT) mediated by PyTPA promotes the release of tumor-associated antigens (TAAs), and primes T lymphocytes . The cytokines coming from the stimulation of PDT and Poly (I:C) promote the activation of T lymphocytes. The high level of chemokines in tumor microenvironment promotes immune cells migration and infiltration in tumor with the assistance of PDT. Finally, through ICB with D PPA-1 peptide, T lymphocytes enhance the recognition of tumor cells and killing tumor cells. Immunogenic cell death induces the release of more TAAs, which will enter the next cycle and complete the full-loop again. Taking advantages of whole cancer-immunity cycle, the cascade amplification nanocomposite achieved almost 100% ORR in vivo . This concept of whole cancer-immunity cycle enhanced immunotherapy provides a novel perspective for tumor treatment.
研究领域:
癌症生物学
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免疫学
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纳米技术
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Ying Luo,Zhongsheng Xu,Qianying Du,Lian Xu,Yi Wang,Jie Xu,Junrui Wang,Sijin Chen,Wenli Zhang,Bo Liu,Jia Liu,Dajing Guo,Yun Liu
The immune landscape of late-stage liver cancer is featured by severe immunosuppression that is characterized by poor immunogenicity, T-cell exhaustion, and infiltration of a large number of immunosuppressive cells, leading to compromised therapeutic efficacy of mainstream immunotherapies. Herein, we developed a pleiotropic immune cell mobilization strategy to modulate immune systems for immunosuppressive liver cancer therapy. In this study, immunogenic bacteria-derived outer membrane vesicles (OMVs) were exploited as a vector to deposit Cu and Mn with mixed valence states via one-step biomineralization, followed by platelet membrane camouflage, which are denoted as OPCM. Mechanistically, the pleiotropic OPCM possesses POD, CAT, and GPX-like activities, thereby achieving cGAS-STING activation, immunogenic ferroptosis, and tumor hypoxia alleviation, ultimately leading to initiation of the cancer immunity cycle, modulation of both innate and adaptive immune system, and reversion of immunosuppression. Notably, the combination with typical αPD-L1 treatment augmented the tumor suppression effect by amplifying the intensity of ferroptosis due to IFN-γ secretion by activated T cells. Overall, the metal biomineralized OPCMs in combination with αPD-L1 formed a closed-loop therapy that cycles from immunotherapy and ferroptosis therapy, providing new insights for treating immunosuppressive liver cancer.
研究领域:
免疫学
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癌症生物学
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生物技术
·
纳米医学
✓ 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）