ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Shanshan Jin,Yongkang Chen,Fahui Li,Ping Yan,Guanhong Guo,Guangzhao Xu,Weiguo Song,Wenda Zhong
Currently, immunotherapy based on photothermal and the application of photodynamic therapy in anti-tumor treatment is showing great potential. Its uniqueness lies in the critical role of small molecule immunomodulators in promoting effective immune responses against tumors, and the use of laser-activated biophysical mechanisms to precisely trigger the swift demise of cancer cells, avoiding damage to surrounding normal tissues. However, the use of photodynamic therapy (PDT) alone is hampered by the tumors’ hypoxic environment, resulting in poor antitumor effects, while photothermal therapy (PTT) alone cannot arouse enough antigen presentation. It is of great significance to design photosensitizers (PSs) that possess both PDT and PTT effects. Herein, a series of PSs with both PDT and PTT efficacy are reported, ultimately selecting Cy7-Naph as the star molecule due to its best overall phototherapeutic effect. Upon reactive oxygen species (ROS) production and thermogenesis in tumor cells, Cy7-Naph induced significant apoptosis and eventually boosted the release of damage-associated molecular patterns (DAMPs) under near-infrared (NIR) light irradiation. By combining Cy7-Naph with the Toll-like receptor agonist Resiquimod (R848), a synergistic treatment for bilateral tumor-bearing mice is achieved. This combination promotes dendritic cell (DC) maturation and increases the infiltration of cytotoxic T lymphocytes (CTLs), leading to significant inhibition of both primary and distant tumors.
研究领域:
生物医学工程
·
肿瘤免疫学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Jingjing Lin,Yushui He,Mofei Yuan,Yuanyuan He,Xiao Wang,Yuan Feng,Mingtao Luo,Ting Lan,Zhen Li,Feng Luo,Jiehua Li,Yanchao Wang,Hong Tan
Traumatic brain injury (TBI) induces a prolonged inflammatory response throughout the damaged brain, which is exacerbated by the sustained accumulation of damage-associated molecular patterns (DAMPs), and consequently impairs endogenous neural regeneration significantly. To mitigate postinjury inflammation and explore the role of positively charged scaffolds in brain repair, two distinct structures of positively charged scaffolds were developed. Both scaffold types effectively reduce inflammation and promote brain tissue repair by eliminating DAMPs, markedly reducing glial scar formation, and promoting angiogenesis in peritrauma areas within 4 weeks of implantation. Notably, scaffolds with cationic backbones exhibit repair outcomes superior to those of other groups due to reduced cellular stimulation and milder chronic inflammation. This study underscores the potential of positively charged scaffolds for central nervous system (CNS) regeneration and provides novel insights into the design of tissue engineering scaffolds for CNS repair.
研究领域:
生物材料
·
神经科学
·
组织工程
·
免疫调节
·
再生医学
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产品关联
DOI
PubMed
高影响因子
Small Methods
·
2020
·Vol. 4
·期 3
·1900799
·
IF 12.13
Yan Peng Jia,Kun Shi,Jin Feng Liao,Jin Rong Peng,Ying Hao,Ying Qu,Li Juan Chen,Li Liu,Xia Yuan,Zhi Yong Qian,Xia Wei Wei
The safety issues and immunological effects of nanosized materials have drawn considerable attention. Gold nanorods (Au NRs) have promising applications in biomedical diagnosis and therapy, but their biosafety and the mechanism underlying in vivo toxicity still remain to be explored. In this study, cetyltrimethylammonium bromide (CTAB) capped Au NRs and PEG modified Au NRs are both prepared, the cytotoxicity evaluation indicates that CTAB-Au NRs of different ratios all exhibit cytotoxicity while PEG-Au NRs show improved biocompatibility. Furthermore, it is investigated how the surface characteristics influence toxical effects of Au NRs both in vitro and in vivo. It is found that CTAB-Au NRs can induce acute cell necrosis, which results in the leakage of damage associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA), subsequently triggering pulmonary inflammation. It is also revealed that the inflammation caused by CTAB-Au NRs is probably mediated by the stimulator of interferon genes (STINGs) signaling pathway. This study explores the cytotoxicity and inflammatory toxicity of CTAB-Au NRs, and how the surface modification affects the toxicity. The molecular pathways for the induction of pulmonary inflammation in vivo are further characterized. These findings might be of importance for designing safer and better gold-based nanomaterials in the future.
研究领域:
纳米技术
·
毒理学
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免疫学
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生物医学工程
✓ 已验证
DOI
高影响因子
ACS Nano
·
2023
·
IF 17.1
Guiyuan Chen,Xiangxia Li,Rui Li,Kecheng Wu,Zhouhang Lei,Ruike Dai,Kyle Roche,Andrew Z. Wang,Yuanzeng Min
Chemotherapeutics have the potential to increase the efficacy of cancer immunotherapies by stimulating the production of damage-associated molecular patterns (DAMPs) and eliciting mutations that result in the production of neoantigens, thereby increasing the immunogenicity of cancerous lesions. However, the dose-limiting toxicity and limited immunogenicity of chemotherapeutics are not sufficient to induce a robust antitumor response. We hypothesized that cancer cells in vitro treated with ultrahigh doses of various chemotherapeutics artificially increased the abundance, variety, and specificity of DAMPs and neoantigens, thereby improving chemoimmunotherapy. The in vitro chemotherapy-induced (IVCI) nanovaccines manufactured from cell lysates comprised multiple neoantigens and DAMPs, thereby exhibiting comprehensive antigenicity and adjuvanticity. Our IVCI nanovaccines exhibited enhanced immune responses in CT26 tumor-bearing mice, with a significant increase in CD4+/CD8+ T cells in tumors in combination with immune checkpoint inhibitors. The concept of IVCI nanovaccines provides an idea for manufacturing and artificial enhancement of immunogenicity vaccines to improve chemoimmunotherapy.
研究领域:
肿瘤学
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免疫学
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药学
·
生物技术
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Jiaying Chang,Man Wang,Junrong Wang,Guoqing Zhu,Yulin Xie,Yanrong Qian,Qianqian Sun,Chunxia Li
Autologous tumor cells demonstrate considerable promise as individualized therapeutic vaccines owing to their endogenous neoantigen repertoire. Nevertheless, their suboptimal immunogenicity substantially impedes clinical translation. Herein, we engineered an innovative whole tumor cell vaccine platform utilizing photothermal Cu 2- x Se nanoparticles, which encapsulate comprehensive tumor-associated antigens and intrinsic immunostimulatory molecules to elicit a polyvalent antitumor immune response. In this work, Cu 2-x Se was applied to prepare the whole tumor cell vaccine for the first time. As a pyroptosis inducer, Cu 2-x Se triggered the expression of damage-associated molecular patterns (DAMPs) as endogenous adjuvants in 4T1 cells (mouse breast cancer cells) under near-infrared (NIR) irradiation. Repeated freeze-thaw cycles inactivated and lysed Cu 2-x Se-loaded 4T1 cells, releasing DAMPs for laser-activated Cu 2-x Se-based whole tumor cell vaccine (LC-TCV) preparation. Mild photothermal therapy (PTT) at the vaccination site by NIR irradiation effectively suppressed tumor growth. This efficacy was primarily attributed to the synergistic effects of multiple natural antigens and adjuvants in LC-TCV, which promoted dendritic cells (DCs) maturation and subsequent immune activation. Consequently, it potentiates the recruitment of cytotoxic T lymphocytes, elicits immunogenic cell death (ICD), and consequently initiates a potent antigen-specific immune cascade. Collectively, this study presents an innovative approach to unleash the potential of personalized whole tumor cell vaccines in cancer therapy.
研究领域:
癌症免疫治疗
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纳米医学
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光热治疗
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疫苗研发
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肿瘤免疫学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Kaiyuan Liu,Pengfei Zan,Zihua Li,Hengli Lu,Peng Liu,Li Zhang,Hongsheng Wang,Xiaojun Ma,Feng Chen,Jing Zhao,Wei Sun
The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here we present a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable systemic antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study offers a comprehensive approach to treat OS by mild photothermal therapy and modulating the immune microenvironment, exhibiting considerable potential in addressing the constraints associated with current therapeutic modalities. This article is protected by copyright. All rights reserved
研究领域:
癌症治疗
·
免疫学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Xiaokang Zhu,Li Xie,Jinming Tian,Yang Jiang,Erqun Song,Yang Song
Ferroptosis has emerged as a promising strategy for treating triple-negative breast cancer (TNBC) due to bypassing apoptosis and triggering immunogenic cell death (ICD) of tumor cells. However, the antitumor efficacy has been limited by the insufficient intracellular ferrous iron concentration required for ferroptosis and inadequate antitumor immune response. To address these limitations, we designed a multi-mode nano-platform (MP-FA@R-F NPs), which exhibited a synergistic effect of ferroptosis, apoptosis and induced immune response for enhanced antitumor therapy. MP-FA@R-F NPs target folate receptors, which are over-expressed on the tumor cell's surface to promote intracellular uptake. The cargoes, including Rhein and Fe 3 O 4 , would be released in intracellular acid, accelerating by NIR laser irradiation. The released Rhein induced apoptosis of tumor cells mediated by the caspase 3 signal pathway, while the released Fe 3 O 4 triggered ferroptosis through the Fenton reaction and endowed the nanoplatform with magnetic resonance imaging (MRI) capabilities. In addition, ferroptosis-dying tumor cells could release damage-associated molecular patterns (DAMPs) to promote T cell activation and infiltration for immune response and induce immunogenic cell death (ICD) for tumor immunotherapy. Together, MP-FA@R-F NPs represent a potential synergistic ferro-/chemo-/immuno-therapy strategy with MRI guidance for enhanced antitumor therapy. Statement of significance The massive strategies of cancer therapy based on ferroptosis have been emerging in recent years, which provided new insights into designing materials for cancer therapy. However, the antitumor efficacy of ferroptosis is still unsatisfactory, mainly due to insufficient intracellular pro-ferroptotic stimuli. In the current study, we designed a multi-mode nano-platform (MP-FA@R-F NPs), which represented a potential synergistic ferro-/chemo-/immuno-therapy strategy with MRI guidance for enhanced antitumor therapy.
研究领域:
癌症治疗
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纳米技术
·
免疫学
·
分子生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 11
·期 2
·518-532
·
IF 7.59
Siyu Ma,Xiao Liang,Ning Yang,Jie Yang,Jun Zhang,Xiuhua Pan,Yawen Wei,Zengyi Liu,Qi Shen
Until now, treatment of refractory tumors and uncontrolled metastasis by cancer immunotherapy has not yet achieved satisfactory therapeutic results due to the insufficient in vivo immune response. Here, we proposed the construction of a therapeutic cancer nanovaccine Fe@OVA-IR820 with ferroptosis-inducing and photothermal properties for boosting cancer immunotherapy. Fe3+ ions were chelated inside the exogenous antigen ovalbumin (OVA) by biomineralization to form the nanovaccine, to which the photosensitizer IR820 was loaded by electrostatic incorporation. After intratumoral injection, in situ immunogenic cell death (ICD) was triggered as a result of Fe3+-dependent ferroptosis. Endogenous neoantigens and damage-associated molecular patterns (DAMPs) were released because of ICD and worked synergically with the exogenous OVA to provoke the immune response, which was further amplified by the photothermal effect after near-infrared irradiation. The enhanced recruitment and infiltration of T cells were observed and resulted in the suppression of the primary tumor. The therapeutic regiment that combined Fe@OVA-IR820 nanovaccine with cytotoxic T lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade significantly boosted anti-cancer immunity and inhibited the growth of distal simulated metastases. Therefore, we proposed Fe@OVA-IR820 nanovaccine combined checkpoint blockade as a potential therapeutic strategy for melanoma treatment.
研究领域:
癌症研究
·
纳米技术
·
免疫治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Chengcheng Wang,Jiao Wang,Xue Pan,Shuang Yu,Meiqi Chen,Yan Gao,Zilin Song,Haiyang Hu,Xiuli Zhao,Dawei Chen,Fei Han,Mingxi Qiao
As a non-apoptotic cell death form, ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance. However, accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms. To address this issue, we prepared a Buthionine-(S,R)-sulfoximine (BSO) loaded metal organic framework (MOF) of BSO-MOF-HA (BMH) with the combination effect of boosting oxidative damage and inhibiting antioxidative defense. MOF nanoparticle was constructed by the photosensitizer of [4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid)] (TCPP) and the metal ion of Zr6, which was further decorated with hyaluronic acid (HA) in order to impart active targeting to CD44 receptors overexpressed cancer cells. BMH exhibited a negative charge and spherical shape with average particle size about 162.5 nm. BMH was found to restore the susceptibility of 4T1 cells to ferroptosis under irradiation. This was attributed to the combination of photodynamic therapy (PDT) and γ-glutamylcysteine synthetase inhibitor of BSO, shifting the redox balance to oxidative stress. Enhanced ferroptosis also induced the release of damage associated molecular patterns (DAMPs) to maturate dendritic cells and activated T lymphocytes, leading to superior anti-tumor performance in vivo . Taken together, our findings demonstrated that boosting oxidative damage with photosensitizer serves as an effective strategy to reverse ferroptosis resistance.
研究领域:
癌症生物学
·
纳米医学
·
药学
·
细胞生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Bulletin
·
2024
·
IF 18.8
Gang Wang,Jingrui Li,Shumin Sun,Yuqi Yang,Zhihui Han,Zifan Pei,Liang Cheng
Excess intracellular H 2 S induces destructive mitochondrial toxicity, while overload of Zn 2+ results in cell pyroptosis and potentiates the tumor immunogenicity for immunotherapy. However, the precise delivery of both therapeutics remains a great challenge. Herein, an electrically activable ZnS nanochip for the controlled release of H 2 S and Zn 2+ was developed for enhanced gas-ionic-immunotherapy (GIIT). Under an electric field, a locality with particularly high concentrations of H 2 S and Zn 2+ was established by the voltage-controlled degradation of the ZnS nanoparticles (NPs). Consequently, the ZnS nanochip-mediated gas-ionic therapy (GIT) resulted in mitochondrial membrane potential depolarization, energy generation inhibition, and oxidative stress imbalance in tumor cells. Interestingly, the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway was activated due to the mitochondrial destruction. Moreover, the released Zn 2+ resulted in the increase of the intracellular Zn levels and cell pyroptosis, which enhanced the immunogenicity via the release of damage-associated molecular patterns (DAMPs). In vitro and in vivo studies revealed that the ZnS nanochip-based GIT effectively eliminated the tumors under an electric field and mobilized the cytotoxic T lymphocytes for immunotherapy. The combination with αCTLA-4 further promoted the adaptive immune response and inhibited tumor metastasis and long-term tumor recurrence. This work presented an electrically activable ZnS nanochip for combined immunotherapy, which might inspire the development of electric stimulation therapy.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Jiang Tao,Tang Zixiang,Tian Shumiao,Tang Haitian,Jia Zhekun,Li Fangjian,Qiu Chenyue,Deng Lin,Ke Lang,He Pan,Liu Gang,Chu Chengchao,Xiong Yongfu
Sonodynamic therapy (SDT) exhibits clinical potential for deep-tissue tumor treatment due to its deep tissue penetration and spatiotemporal controllability. Its core mechanism relies on ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. However, conventional sonosensitizers face limitations in ROS yield and tumor-targeting efficiency. In this study, we innovatively designed a multifunctional metal–organic nanosheet (TiZrRu-MON) by hydrothermal coordination of [Ru(bpy)₃] 2 ⁺ photosensitizing units with TiZr-O clusters, while incorporating Fe 3 ⁺ to construct a cascade catalytic system. Experimental results demonstrated that: (1) Fe 3 ⁺ lattice doping significantly enhanced charge carrier mobility and ultrasound-triggered 1 O₂ quantum yield via the formation charge transfer channels; (2) The acidic tumor microenvironment activated Fe 3 ⁺-mediated Fenton reactions, establishing a positive feedback loop with SDT to synergistically amplify ROS generation; (3) Hyaluronic acid functionalization improved nanosheet internalization in HepG2 tumor cells through CD44 receptor-mediated endocytosis. Remarkably, ultrasound irradiation induced substantial oxidative stress and immunogenic cell death, promoting the release of damage-associated molecular patterns (DAMPs), which elevated the maturation rate of tumor-infiltrating dendritic cells (DCs) and significantly increased the proportion of CD8⁺ T cells. In a mouse subcutaneous tumor model, the system achieved effective tumor suppression with manageable systemic toxicity. This work proposes a metal–ligand coordination strategy to advance the development of high-performance sonosensitizers and immunomodulatory antitumor technologies. Graphical
研究领域:
纳米医学
·
癌症治疗
·
生物无机化学
·
生物医学工程
·
免疫治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2024
·Vol. 53
·期 20
·8772-8780
·
IF 3.5
Kai Xie,Xing-Yun Lu,Hou Zhu,Lin-Yuan Zhu,Rong-Tao Li,Rui-Rong Ye
A series of Ir(III)–naproxen (NPX) conjugates with the molecular formula [Ir(C^N)2bpy(4-CH2ONPX-4′-CH2ONPX)](PF6) (Ir-NPX-1–3) were designed and synthesized, including C^N = 2-phenylpyridine (ppy, Ir-NPX-1), 2-(2-thienyl)pyridine (thpy, Ir-NPX-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-NPX-3). Cytotoxicity tests showed that Ir-NPX-1–3 exhibited excellent antitumor activity, especially in A549R cells. The cellular uptake experiment showed that the complexes were mainly localized in mitochondria, and induced apoptosis in A549R cells by damaging the structure and function of mitochondria. The main manifestations are a decrease in the mitochondrial membrane potential (MMP), an increase in reactive oxygen species (ROS) levels, and cell cycle arrest. Furthermore, Ir-NPX-1–3 could inhibit the migration and colony formation of cancer cells, demonstrating potential anti-metastatic ability. Finally, the anti-inflammatory and immunological applications of Ir-NPX-1–3 were verified. The downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1) expression levels and the release of immunogenic cell death (ICD) related signaling molecules such as damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP)) indicate that these Ir(III) –NPX conjugates are novel ICD inducers with synergistic effects in multiple anti-tumor pathways.
研究领域:
肿瘤学
·
药物化学
·
细胞生物学
·
免疫学
✓ 已验证
DOI
高影响因子
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