Advanced Healthcare Materials
·
2022
·Vol. 11
·期 12
·2102781
·
IF 11.092
Yutong Liu,Hui Li,Huajun Zhao,Yanyun Hao,Simon Van Herck,Zejun Xu,Guan Wang,Xiao Wang,Xinke Zhang,Xiaoyan Ge,Xia Li,Ailu Yang,Hongfei Chen,Jing Zou,Wentao Wang,Bruno G. De Geest,Zhiyue Zhang
In situ anti-tumor vaccination is an attractive type of cancer immunotherapy which relies on the effectiveness of dendritic cells (DCs) to engulf tumor antigens, become activated, and present antigens to T cells in lymphoid tissue. Here, a multifunctional nanocomplex based on calcium crosslinked polyaspartic acid conjugated to either a toll-like receptor (TLR)7/8 agonist or a photosensitizer is reported. Intratumoral administration of the nanocomplex followed by laser irradiation induces cell killing and hence generation of a pool of tumor-associated antigens, with concomitant promotion of DCs maturation and expansion of T cells in tumor-draining lymph nodes. Suppression of tumor growth is observed both at the primary site and at the distal site, thereby hinting at successful induction of an adaptive anti-tumor response. This strategy holds promise for therapeutic application in a pre-operative and post-operative setting to leverage to mutanome of the patient's own tumor to mount immunological memory to clear residual tumor cells and metastasis.
研究领域:
癌症免疫疗法
·
纳米技术
·
免疫学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Jia-Qi Luo,Yong-Cong Huang,Jing-Yang Zhang,Qi-Song Tong,Areesha Batool,Jinzhi Du,Yuyou Duan
Antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs) are key players in modulating the immune responses of cytotoxic T lymphocytes (CTLs). Resiquimod (R848), a toll-like receptor (TLR) agonist, has demonstrated the capacity to enhance APC function and reprogram the phenotype of macrophages; however, the unfavorable in vivo performance constrains its therapeutic potential. Here, we developed R848-loaded mesoporous silica nanoparticles (denoted as R848@MSN-bi-PEG) with pH-responsive surface PEG detachment to effectively modulate APCs. The acidic tumor pH triggered PEG detachment when R848@MSN-bi-PEG accumulated at the tumor site, thereby promoting APC uptake and R848 release, which facilitated DCs maturation and macrophage repolarization to a pro-inflammatory phenotype. The in vivo antitumor study indicated that R848@MSN-bi-PEG led to potent anti-tumor immunity by modulating the immunosuppressive tumor microenvironment. This approach offers a novel strategy to improve the effectiveness of cancer immunotherapy.
研究领域:
生物医学工程
·
免疫学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Mengyao Ma,Ximu Li,Mingyuan Zhong,Xuejing Li,Jiang Yu,Zhaomeng Wang,Qingzhi Lv,Xin Li,Zhonggui He,Hongzhuo Liu,Yongjun Wang
Cancer vaccines, a critical technology in cancer immunotherapy, have shown great therapeutic potential. However, traditional vaccines based on tumor cell lysates (TCLs) have shown disappointing results in early clinical trials due to low immunogenicity, in vivo instability, and the inability to codeliver with adjuvants. To address these issues, we developed a nanoparticle vaccine, R848-GA@TCLs, by modifying the toll-like receptor 7/8 (TLR7/8) agonist R848 with gallic acid. This nanovaccine leverages the “capturing” ability of the galloyl moiety to coload TCLs and R848, forming stable nanoparticles. R848-GA@TCLs efficiently target lymph nodes, increasing TCL accumulation 10-fold, and enable the synchronized release of antigens and adjuvants within dendritic cells (DCs). Our results show that R848-GA@TCLs increase with respect to the cross-presentation of tumor antigens, promote the production of pro-inflammatory cytokines, and activate DCs, leading to a significant increase in effector T cells, natural killer (NK) cells, and M1 macrophages. This strong immune response resulted in potent antitumor effects, with R848-GA@TCLs demonstrating efficacy in multiple tumor models by significantly inhibiting tumor growth and metastasis. In conclusion, R848-GA@TCLs represent a personalized cancer vaccine capable of codelivering TCLs and adjuvants, eliciting robust antitumor immune responses, and hold great potential for clinical applications.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 20
·6940-6949
·
IF 6.843
Guiqiang Zhang,Ning Wang,Haifeng Sun,Xiao Fu,Shumei Zhai,Jiwei Cui
Combination cancer immunotherapy that synergizes the advantages of multiple therapeutic agents has shown great potential in tumor treatment. Herein, we report the one-step assembly of therapeutic nanoparticles (NPs) to co-deliver photosensitizers and adjuvants for combination photodynamic therapy (PDT) and immunotherapy. The NPs are obtained via self-assembly of chlorin e6 (Ce6) and imidazoquinoline-based TLR7 agonists (IMDQ), which results in a high loading efficacy of 72.2% and 27.8% for Ce6 and IMDQ, respectively. Upon laser irradiation, the resulting NPs could not only effectively induce photodynamic immunogenic cancer cell death, but also elicit robust antitumor immunity, leading to significant inhibition of both primary and distant tumors in a bilateral tumor model. This study demonstrates the potential of self-assembled NPs in co-delivering multiple therapeutics for potential immunotherapy to enhance the antitumor efficacy.
研究领域:
生物医学工程
·
肿瘤免疫学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2026
·
IF 17.3
Yuan Gao,Shiyu Yuan,Jiaqi Zhang,Fangming Liang,Yue Wang,Yinan Song,Ning Li,Zhaochu Xu,Yan Zhao,Yongjun Wang,Hongzhuo Liu
In situ cancer vaccination is limited when antigens diffuse or degrade, adjuvants act systemically, and the timing of immune licensing is misaligned. Here, we report a penetrate-then-gate design that decouples distribution from activation. Complementary, clickable poly(propylene sulfide) (PPS) nanoparticles (∼25 nm) first penetrated the tumor parenchyma after intravenous administration. Brief near-infrared irradiation then gated intracellular ROS generation by a photosensitizer (PPa), oxidizing PPS to poly(propylene sulfone) (PPSU), exposing azide/DBCO handles, and driving in situ assembly. The resulting PPSU network captured endogenous antigens, thereby colocalizing antigen availability with TLR7/8 agonist (IMDQ). In mice, optical imaging indicated earlier and sustained intratumorally exposure at irradiation for coadministration (the two formulations premixed before injection) versus sequential dosing (PPa-PPSN3 first, followed by IMDQ-PPSDBCO before irradiation), aligning exposure with the licensing window. Across multiple cancer models, coadministration improved primary control, elicited rechallenge protection, and suppressed distant growth, with restrained systemic cytokines. This work applies a spatiotemporal alignment principle for in situ vaccination to achieve precise and durable tumor immunotherapy in a modular way.
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 10.2
Yuxiu Wang,Haoyang Yuan,Ye Zhang,Yu Zhang,Tian Yin,Haibing He,Xing Tang,Yanjiao Wang,Jingxin Gou,Guofei Li
The immunosuppressive tumor microenvironment and poor drug targeting remain major obstacles in bladder cancer (BC) therapy. To address this, a combination strategy integrating chemotherapy and immunotherapy was employed by co-delivering epirubicin (EPI) and the immune modulator imiquimod (IMQ) using a folate-modified nanocarrier. A hydroxyethyl starch-based epirubicin prodrug modified with folic acid (FA-HES-EPI) was first synthesized to improve tumor selectivity. FA-HES-EPI/IMQ micelles were then fabricated via nanoprecipitation by encapsulating IMQ into the hydrophobic core, aiming to achieve synergistic therapeutic efficacy. Folate modification conferred tumor-targeting capability to the micelles and promoted efficient cellular uptake via folate receptor–mediated endocytosis. The acid-sensitive hydrazone bond enabled controlled release of both EPI and IMQ in the acidic tumor microenvironment, thereby enhancing their combined chemo-immunotherapeutic effects. In an orthotopic BC model, FA-HES-EPI/IMQ micelles significantly enhanced drug accumulation at the tumor site, repolarized M2-type tumor-associated macrophages (TAMs) toward the M1 phenotype, remodeled the tumor stroma, and achieved a tumor inhibition rate of 96.7 %, markedly surpassing that of FA-HES-EPI micelles (86.6 %) and free EPI (62.3 %), with negligible systemic toxicity. This pH-responsive co-delivery system represents a promising approach to improve both efficacy and safety in bladder cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2023
·
IF 12.4
Jiqian Zhang,Shasha Zhu,Mingxu Zhao,Mengni Zhou,Xiaoling Zhu,Xin Qing,Zhilai Yang,Pengfei Wei,Guoying Zhang,Weiling He,Yongqiang Yu,Xuesheng Liu
Rationale: Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety. Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems. Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed. Methods: The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT. Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain. Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT. Results: PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1. A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia. More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed. In the hydrogel system, imiquimod primes tumor-specific CD8 + T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8 + T cells through upregulating MHC-I. Consequently, the hydrogel maximumly increases CD8 + T cells infiltration into tumor and potentiates PTT efficacy. Conclusion: This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.
研究领域:
癌症治疗
·
生物医学工程
·
药学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Infectious Diseases
·
2023
·
IF 5.3
Wenzhu Yin,Bihua Deng,Zeyu Xu,Haiyan Wang,Fang Ma,Mingxu Zhou,Yu Lu,Jinqiu Zhang
Adjuvants are essential for the induction of robust immune responses against vaccine antigens. Small-molecule TLR7 agonists hold high potential for this purpose. In this communication, imiquimod (IMQ) bearing a cholesterol lipid moiety derivative, IMQ-Chol, was designed and synthesized as a vaccine adjuvant, which could release parent IMQ molecules in aqueous conditions via amide bond hydrolysis. We performed a series of immunological evaluations by cooperating with the inactivated foot-and-mouth disease virus (FMDV). All of the results confirmed that IMQ-Chol could stimulate the body for a prolonged time to produce strong humoral and cellular immunity with a balanced Th1/Th2 immune response through a TLR7-related MAPK pathway. In addition, the results of the proof-of-concept vaccine indicated IMQ-Chol had a good effect on preventing and treating FMD in pigs.
研究领域:
免疫学
·
病毒学
·
药学
·
兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Advances
·
2022
·Vol. 3
·期 5
·2505-2514
·
IF 0
Wenzhu Yin,Dechun Xuan,Bihua Deng,Mingxu Zhou,Fang Ma,Jinqiu Zhang,Yu Lu
Adjuvants have proven to be integral components in most vaccines for promoting appropriate immune responses at both innate and adaptive levels. Imiquimod (IMQ, R837), an agonist for Toll-like receptors 7 (TLR7), is a potent molecular activator of the innate immune system and has been developed as an adjuvant for immunotherapy. However, due to its pharmacokinetic profile, IMQ may induce strong local and systemic inflammatory reactions and is poorly tolerated. To overcome these hurdles, herein, we conjugate IMQ and lauryl alcohol (LA) to the backbone of biodegradable poly (γ-glutamic acid) (γ-PGA) to prepare an amphiphilic polymer (shortened to γ-PGA-IMQ-LA) with improved stability and biodistribution of IMQ. In order to investigate the distribution of the amphiphilic polymer in vitro and in vivo, fluorescein was grafted to the lateral chain to synthesize fluorescent-labeled γ-PGA-IMQ-LA-FL (shortened to FIP). The novel amphiphilic FIP polymer was characterized via1H NMR, FI-IR, UV-vis, fluorescence spectra and zeta potential. Using ovalbumin (OVA) as a model antigen and FIP as an adjuvant for immunization, the formulations of FIP + OVA in different dosages could significantly promote the production of OVA-specific IgG in mice and prolong immune responses with acceptable safety.
研究领域:
免疫学
·
药剂学
·
聚合物化学
·
生物医学工程
✓ 已验证
产品关联
DOI
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yiting Yang,Ping Ren,Ying Sun,Junyi Li,Xinjun Zhou,Haipeng Zhang,Chengguang He,Huining Dai,Lili Guan
Nostoc commune Vaucher, a terrestrial and benthic blue-green alga, widely used in food and medicine worldwide. N. commune Polysaccharides (NCVP) have excellent biological activities, especially immunomodulatory, hypoglycemic and anti-tumor activities. However, the mechanism and structure-activity relationship of NCVP has been less studied. In this study, based on methylation and NMR results, a novel polysaccharide NCVP2 with 135 kDa, containing→4)-α-D-Gal p -(1→, → 4)-β-D-Glc p -(1→, and →4)-α-D-Xyl p -(1→ residues as the backbon, was sequentially purified from N.commune by DEAE-52 and Sephadex G-100 column. NCVP2 (50 μg/mL) exhibited the strong in vitro immunomodulatory activity by promoting the generation of nitric oxide ( NO ) and reactive oxygen species (ROS). A total of 2048 differentially expressed genes (DEGs) were identified by RNA-seq, including 1019 down-regulated genes and 1065 up-regulated genes. These DEGs were mainly enriched in the immune-related biological processes, involving in Mitogen-activated protein kinase (MAPK) and Toll-like receptor (TLR) signaling pathways by GO and KEGG enrichment analysis. Furthermore, Western blot results proved NCVP2 could recognize TLR2 and TLR4/MD2, and regulate TLR7/IRF7, MAPK and PI3K/AKT signaling pathways. In summary, a novel polysaccharide NCVP2 from N.commun e was proposed to exhibit significant immunomodulatory effects with multiple-paths and targets, and has great potential in the development of healthy foods such as immunomodulators.
研究领域:
免疫学
·
生物化学
·
药理学
·
分子生物学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Ruonan Wang,Huixin Li,Shasha He,Yuanji Feng,Cong Liu,Kai Hao,Danhua Zhou,Xiaoyuan Chen,Huayu Tian
Lymph nodes are crucial immune foci as the primary target for cancer immunotherapy. However, the anti-tumor functions of tumor-draining lymph nodes (TDLNs) are critically suppressed by tumors. Here, a novel spatiotemporal nano-regulator is presented, designed to modulate the dendritic cells (DCs) in TDLNs, establishing a supportive niche for immune surveillance. The DC-mediated nano-regulator (DNR) is established by the self-assembly of an imidazoquinoline (IMDQ) prodrug, inhibitory immune checkpoint (ICP) siRNA, and mannan (a TLR4 agonist). This unique design leverages the spatiotemporal activation of TLR4 and TLR7/8, thereby optimizing DC maturation and cytokine production. This further promotes efficient T cell priming. Simultaneously, the ICP-targeting siRNA mitigates the tolerogenic effects induced by tumor-derived factors and TLR activation, preventing T cell exhaustion. In essence, DNR facilitates potent remodeling of TDLNs and the tumor microenvironment, activating the anti-tumor immunity cascade. When combined with vaccines, DNR greatly promotes tumor regression and the establishment of long-term immunological memory.
研究领域:
癌症免疫疗法
·
免疫学
·
纳米医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2020
·Vol. 16
·期 38
·2003543
·
IF 11.459
Lingqiao Liu,Yi Wang,Xing Guo,Jingya Zhao,Shaobing Zhou
The progress of antitumor immunotherapy is usually limited by tumor-associated macrophages (TAMs) that account for the highest proportion of immunosuppressive cells in the tumor microenvironment, and the TAMs can also be reversed by modulating the M2-like phenotype. Herein, a biomimetic polymer magnetic nanocarrier is developed with selectively targeting and polarizing TAMs for potentiating immunotherapy of breast cancer. This nanocarrier PLGA-ION-R837 @ M (PIR @ M) is achieved, first, by the fabrication of magnetic polymer nanoparticles (NPs) encapsulating Fe 3 O 4 NPs and Toll-like receptor 7 (TLR7) agonist imiquimod (R837) and, second, by the coating of the lipopolysaccharide (LPS)- treated macrophage membranes on the surface of the NPs for targeting TAMs. The intracellular uptake of the PIR @ M can greatly polarize TAMs from M2 to antitumor M1 phenotype with the synergy of Fe 3 O 4 NPs and R837. The relevant mechanism of the polarization is deeply studied through analyzing the mRNA expression of the signaling pathways. Different from previous reports, the polarization is ascribed to the fact that Fe 3 O 4 NPs mainly activate the IRF5 signaling pathway via iron ions instead of the reactive oxygen species-induced NF-κB signaling pathway. The anticancer effect can be effectively enhanced through potentiating immunotherapy by the polarization of the TAMs in the combination of Fe 3 O 4 NPs and R837.
研究领域:
纳米技术
·
癌症免疫学
·
生物医学工程
·
药理学
✓ 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）