Advanced Therapeutics
·
2024
·Vol. 7
·期 8
·2400045
·
IF 3.7
Shanshan Wang,Zhiqiang Bi,Tianming Lu,Ruoning Qian,Jie Yu,Qiang Zhang,Hao Yang,Wenli Lu,Yuanyuan Guo,Xiaoqing Xin,Yong Bian,Ruogu Qi
Colorectal cancer (CRC) stands out as one of the most prevalent gastrointestinal cancers. Current treatment strategies for CRC are significantly hindered by systemic toxicity and suboptimal therapeutic efficacy. This study aims to overcome these limitations by developing a robust tumor-targeting chemo-photothermal strategy, combining Bortezomib (BTZ) as a proteasome inhibitor, IR780 iodide as a near-infrared dye, and Photothermal Therapy (PTT) agent, with hyaluronic acid (HA) serving as the shell for tumor targeting, denoted as HA/PB@IR780. The investigations reveal the impressive tumor-targeting affinity of HA/PB@IR780, leading to a synergistic chemo-photothermal therapeutic effect both in vitro and in vivo. Additionally, this material demonstrates the capability for drug release triggered by low pH conditions. Moreover, HA/PB@IR780 induced the generation of reactive oxygen species (ROS), triggered cells apoptosis via the PERK-CHOP-Bcl-2 pathway, and induced Immunogenic Cell Death (ICD) in CT26 cells. Importantly, HA/PB@IR780 selectively targets tumor sites, mitigating systemic toxic side effects and significantly extending the survival of CT26 tumor-bearing mice. In conclusion, this designed tumor-targeting nanocarrier represents a promising and potentially effective platform for the precise treatment of CRC.
研究领域:
肿瘤学
·
纳米技术
·
药理学
·
细胞生物学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Guanghao Li,Yujun Bao,Hui Zhang,Jingchun Wang,Xiaodan Wu,Rui Yan,Zhiqiang Wang,Yingxue Jin
Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe 3 O 4 -carbon dots complex (Fe 3 O 4 -CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe 3 O 4 -CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe 3 O 4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe 3 O 4 -CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe 3 O 4 -CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1 α ) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe 3 O 4 -CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1 α was investigated by immunofluorescence method. In vivo, Fe 3 O 4 -CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe 3 O 4 -CDs@Fc is a promising immune-antitumor drug.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
免疫疗法
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Silin Du,Guangyu Ma,Xiang Li,Minghao Chao,Liying Fan,Zhiqiang Zhao,Rongze Tang,Junjie Li,Chaonan Jing,Yufan Liu,Dehong Yu,Zhao Liu,Fenglei Gao
To overcome the resistance of tumor cells to death through a single pathway, PANoptosis, a novel synergistic mode of cell death, can simultaneously activates pyroptosis, apoptosis, and necroptosis. Most current strategies for inducing PANoptosis focused on amplifying reactive oxygen species (ROS) through exogenous stimuli, while the regulatory role of tumor cell metabolic characteristic in this process has long been overlooked. We propose a ROS-Metabolism dual axis synergistic induction of PANoptosis, simultaneously enhancing antitumor immune responses, and construct a novel bionic nanoplatform named CVOVM. This platform consists of CoVO x nanocakes and the glutamine transporter inhibitor V-9302, with 4T1 cell membranes as camouflage. In tumors, CVOVM initiates a series of catalytic reactions: CoVO x promotes numerous ROS generation, while V-9302 disrupts glutamine metabolism, depleting glutathione (GSH) and nicotinamide adenine dinucleotide (NAD + ), thereby triggering the assembly of PANoptosome primarily composed of NLRP3 and NLRC5, which initiates pyroptosis, apoptosis, and necroptosis. The occurrence of PANoptosis promotes immunogenic cell death (ICD) to remodel tumor immunosuppressive microenvironment, and enhances immunotherapy and inhibits lung metastasis. Overall, we present a previously unreported mechanis to achieve the synergistic induction of PANoptosis through ROS amplification and metabolic inhibition, enhancing antitumor immunity, and potentially providing new opportunities and possibilities for combination cancer therapy.
研究领域:
癌症研究
·
纳米医学
·
免疫治疗
·
细胞死亡机制
·
活性氧信号通路
·
肿瘤代谢
·
仿生纳米材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2022
·
IF 18.962
Hao Tian,Guohao Wang,Wei Sang,Lisi Xie,Zhan Zhang,Wenxi Li,Jie Yan,Ye Tian,Jie Li,Bei Li,Yunlu Dai
Dendritic cells (DCs) play a key role in the presentation of tumor antigens to initiate innate and adaptive immune responses. While the tumor microenvironment (TME) contains a network of immunosuppressive factors that inhibit the differentiation and maturation of DCs. Immunoadjuvants have been focusing on modulating DCs function to improve cancer immunotherapy . Herein, a phenolic nanoadjuvant was developed by self-assembly of the sonosensitizer polymer (PEG-b-IR), GSH inhibitor (sabutoclax), Mn 2+ and TME acidic sensitive phenolic polymer (PEG-b-Pho) via metal–phenolic coordination. The combinational action of SDT-mediated ICD effect and Mn 2+ promoted the activation of the cGAS-STING pathway significantly enhanced DCs maturation. Furthermore, this phenolic nanoadjuvant greatly sensitizes tumors to PD-L1 checkpoint blockade immunotherapy, resulting in efficiently inhibiting the growth of distant tumors and restraining lung metastasis. Therefore, our work provides the potential to remedy the therapeutic limitation of insufficient antitumor immunity for enhanced cancer immunotherapy.
研究领域:
癌症研究
·
免疫学
·
纳米技术
·
治疗学
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Xingru Zhao,Xingyi Wan,Tian Huang,Shuncheng Yao,Shaobo Wang,Yiming Ding,Yunchao Zhao,Zhou Li,Linlin Li
Recently, with the rational design of transition metal-containing nanoagents, chemodynamic therapy (CDT) has been developed and considered a promising method for cancer therapy through Fenton and Fenton-like reaction-induced hydroxyl radical (·OH) generation and cellular oxidative damage. However, it is still a great challenge to realize high reactive oxygen species (ROS) generation and therapeutic efficiency under the strict conditions of the tumor microenvironment (TME). Herein, we design and fabricate a TME-responsive core-shell nanocage composed of a CaCO 3 nanolayer and a heterogeneous CoP core (CaCO 3 @CoP, CCP) with the synergy of CDT and calcium overload to maximize oxidative damage and enhance cancer therapy. The CaCO 3 nanoshell is sensitive to pH and can be rapidly degraded upon endocytosis, leading to intracellular Ca 2+ accumulation, which further triggers the production of mitochondrial ROS. Subsequently, the CoP hollow nanocage with fully exposed Co active sites has high Fenton-like reactive activity to produce ·OH and induce mitochondrial damage. Mitochondrial damage and ROS elevation, in turn, can modulate Ca 2+ dynamics and augment calcium overload. The reciprocal interaction and loop feedback between calcium overload and photoenhanced ROS generation via photothermal therapy (PTT) can further trigger the immunogenic cell death (ICD) process to activate the maturation of dendritic cells (DCs), activation of cytotoxic and helper T cells, and excretion of proinflammatory cytokines to enhance antitumor immunity in vivo. With the butterfly effect, CCP finally brings forth a greatly enhanced cancer therapeutic outcome in murine models.
研究领域:
纳米技术
·
癌症研究
·
治疗学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Jiao Zheng,Jiangchuan Sun,Jia Chen,Shenyin Zhu,Shuning Chen,Yujiao Liu,Lan Hao,Zhigang Wang,Shufang Chang
Immunotherapy by stimulating the host immune system has been a promising therapeutic strategy for advanced ovarian cancer . Here we describe a treatment strategy that combines chemotherapy and photo-sonodynamic therapy (PSDT) to induce systemic antitumor immunity. We have successfully fabricated phase-changeable core-shell nanoparticles (OIX_NPs), which carry oxygen in the core and the photosensitizer indocyanine green (ICG)/oxaliplatin (OXP) in the shell for our combination therapy. In the present study, we demonstrated that OIX_NPs have great potential as contrast agents to enhance photoacoustic (PA) imaging. Furthermore, our combined strategy could induce immunogenic cell death (ICD) by promoting surface exposure of calreticulin (CRT) and passive release of high-mobility group box 1 (HMGB1). Importantly, it could inhibit the growth not only primary tumors but also distant tumors in a bilateral syngeneic mouse model by increasing intratumor infiltration of cytotoxic T lymphocytes . In conclusion, the combination of chemotherapy and PSDT has the potential to enhance antitumor immunity significantly and achieve the integration of diagnosis and treatment for ovarian cancer.
研究领域:
癌症研究
·
免疫学
·
纳米医学
·
化疗
·
诊疗一体化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Pengcheng Hu,Yongxin Li,Luchen Zhang,Xiaopeng Lan,Xiaochuan Ren,Wenlong Liang,Shen Wang,Yizhen Wang,Yanhui Zhao,Yanhui Zhang,Chunzhao Liu,Chunlei Liu
Cuproptosis is a newly recognized copper-dependent nonapoptotic form of cell death, which stimulate studies exploring copper-based nanomaterials to treat cancer through distinct mechanistic action. However, it remains a challenge to completely eradicate tumors via monotherapy. Herein, a copper-doped BiSe x (CBS) nanozyme was developed to boost αPD-L1-mediated immune checkpoint blocking (ICB) via synergetic apoptosis/cuproptosis-induced immunogenic cell death (ICD). The defect-engineered CBS nanozyme exhibits strong peroxidase-mimicking activities and generates abundant reactive oxygen species (ROS) production causing cell apoptosis, which could be further augmented by NIR photoirradiation. Meanwhile, the CBS could cause mitochondrial lipoylated protein aggregation, leading to cell cuproptosis. The photothermal/catalytic/cuproprosis synergistic therapy triggered by CBS nanozyme combined with αPD-L1 antibody effectively inhibits the growth of primary tumors and distant tumors in prostate cancer model. Furthermore, CBS nanozyme exhibited significant germicidal effect in wound infection. Collectively, this work provides a new insight into cancer treatment of copper-based nanozyme based on cuproptosis/apoptosis-related combined therapy.
研究领域:
癌症治疗
·
纳米技术
·
免疫疗法
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Meng Wei,Xiaobo Wang,Yunhai Mo,Cunqing Kong,Mengqi Zhang,Guanhua Qiu,Zhihong Tang,Jie Chen,Feixiang Wu
Introduction Current therapeutic strategies, including immune checkpoint blockade (ICB), exhibit limited efficacy in treating hepatocellular carcinoma (HCC). Nanoparticles, particularly those that can accumulate specifically within tumors and be activated by sonodynamic therapy (SDT), can induce immunogenic cell death (ICD); however, ICD alone has not achieved satisfactory therapeutic effectiveness. This study investigates whether combining ICB with ICD induced by nanoparticle-mediated SDT could enhance anti-tumor immunity and inhibit HCC growth.Methods We developed an iron-based micelle nanodelivery system encapsulating the Near-Infrared Dye IR-780, which was surface-modified with a cyclic tripeptide composed of arginine-glycine-aspartic acid (cRGD). This led to the synthesis of targeted IR780@FOM-cRGD nanoparticles. These nanoparticles were specifically engineered to kill tumor cells under sonication, activate immunogenic cell death (ICD), and be used in conjunction with immune checkpoint blockade (ICB) for the treatment of hepatocellular carcinoma (HCC).Results The synthesized IR780@FOM-cRGD nanoparticles had an average diameter of 28.23±1.750 nm and a Zeta potential of −23.95±1.926. Confocal microscopy demonstrated that IR780@FOM-cRGD could target HCC cells while minimizing toxicity to healthy cells. Upon sonodynamic activation, these nanoparticles consumed significant amounts of oxygen and generated substantial reactive oxygen species (ROS), effectively killing tumor cells and inhibiting the proliferation, invasion, and migration of H22 cells. Hemolysis assays confirmed the in vivo safety of the nanoparticles, and in vivo fluorescence imaging revealed significant accumulation in tumor tissues. Mouse model experiments showed that combining ICB(which induced by Anti-PD-L1) with ICD (which induced by IR780@FOM-cRGD), could effectively activated anti-tumor immunity and suppressed tumor growth.Discussion This study highlights the potential of IR780@FOM-cRGD nanoparticles to facilitate tumor eradication and immune activation when used in conjunction with Anti-PD-L1 therapy. This combination represents a non-invasive, efficient, and targeted approach for the treatment of hepatocellular carcinoma (HCC). By integrating sonodynamic therapy with immunotherapy, this strategy promises to substantially improve the effectiveness of traditional treatments in combating HCC, offering new avenues for clinical application and therapeutic innovation.
研究领域:
肿瘤学
·
纳米技术
·
免疫治疗
·
癌症生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Meiting Li,Yaqian Zhang,Xiaoge Zhang,Zhuoyin Liu,Junjie Tang,Miao Feng,Baizhu Chen,Dalin Wu,Jie Liu
Sonodynamic therapy (SDT) benefiting from its intrinsic merits, such as noninvasiveness and deep tissue penetrability, is receiving increasing considerable attention in reactive oxygen species (ROS)-based tumor treatment. However, current sonosensitizers usually suffer from low tumor lesion accumulation, insufficient ROS generation efficiency under ultrasound, and non-biodegradability, which seriously impede the therapeutic outcomes. Additionally, it is difficult that SDT alone can completely eradicate tumors because of the complex and immunosuppressive tumor microenvironment (TME). Herein, we simultaneously employ sonosensitive porphyrin building blocks and glutathione (GSH)-responsive disulfide bonds to construct a novel degradable multifunctional porphyrin-based hollow porous organic polymer (POP) nanosonosensitizer (H-Pys-HA@M/R), which combine SDT, “on-demand” chemotherapy, and immunotherapy. Taking the unique advantages of POPs with designable structures and high specific surface area, this H-Pys-HA@M/R nanosonosensitizer can achieve tumor target accumulation, GSH-triggered drug release, and low-frequency ultrasound-activating ROS generation with encouraging results. Furthermore, this multifunctional nanosonosensitizer can effectively evoke immunogenic cell death (ICD) response through the combination of SDT and chemotherapy for both primary and distal tumor growth suppression. Meanwhile, H-Pys-HA@M/R exhibits favorable biodegradation and biosafety. Therefore, this study provides a new strategy for reasonably designing and constructing POP-related sonosensitizers combining SDT/chemotherapy/immunotherapy triple treatment modalities to eradicate malignant tumors.
研究领域:
生物医学工程
·
癌症治疗
·
纳米技术
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 5
·1876-1894
·
IF 6.6
Guoyun Wan,Xuheng Chen,Jiayu Chen,Ruiling Gou,Haijiao Wang,Shuhao Liu,Mingyang Zhang,Hongli Chen,Dan Wang,Qiqing Zhang
Recurrence and metastasis are the main reasons for failure in the treatment of triple-negative breast cancer (TNBC). Phototherapy, one of the most well-known potent cancer treatment models is highlighted by ablating primitive tumors with immunogenic cell death (ICD) and is associated with endoplasmic reticulum (ER) stress to elicit long-lasting anti-tumor immunity. However, the provoked inflammatory response after phototherapy will stimulate angiogenesis, which provides nutrition for tumor recurrence. Here, an ER-targeted nanoplatform was constructed based on hollow mesoporous Cu2−XS (HMCu2−XS) nanoparticles to suppress recurrence and metastasis of TNBC by combining photo-ablation and microenvironment remodeling. Profiting from the metal ion coordination and large hollow space, HMCu2−XS can be easily modified with p-toluenesulfonamide for ER-targeting and quantitatively loaded celecoxib (CXB) as a vascular inhibitor, thus obtaining ER-HMCu2−XS/CXB. ER-HMCu2−XS showed great photothermal and photodynamic efficiency for ablating 4T1 tumors and inducing ICD under NIR-II laser irradiation. Compared with non-ER-targeted nanosystems, the ER-targeted nanosystem elicited stronger ICDs and recruited more immune cells. Moreover, the thermal-responsively released CXB successfully inhibited angiogenesis after photothermal therapy. The data showed that the ER-HMCu2−XS/CXB mediated the triplicate therapeutic effect of photo-ablation, immune response activation, and vascular suppression effectively, preventing the recurrence and metastasis of TNBC. In conclusion, this work provides a synergistic strategy to enhance therapeutic outcomes in TNBC.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Li Tan,Zhang Xingyu,Shi Chengyu,Liu Qiao,Zhao Yuetao
Combination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, β-Methyleneadenosine 5′-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.
研究领域:
纳米技术
·
癌症免疫治疗
·
光热疗法
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Zhijun Miao,Anan Xu,Gang Shen,Siyi Tang,Jie Luo,Jiajian Yang,Zhe Chen,Jinxian Pu,Tao Yang
Immunogenic cell death (ICD) induced by chemotherapeutics holds promise for cancer therapy, but limited drug penetration across the bladder mucosa and an immune-excluded tumor microenvironment (TME) have hindered success in bladder cancer. Here, we develop fluorinated albumin nanocages as transmucosal delivery vesicles that concurrently target cancer-associated fibroblasts (CAFs) and tumor cells to potentiate chemoimmunotherapy. Surface fluorination enables mucosal penetration, while recognition of secreted protein acidic and cysteine-rich (SPARC) protein ensures selective uptake by CAFs and tumor cells. Encapsulated chemotherapeutics enhance ICD through inhibition of the Bcl-2 pathway, promoting tumor cell death. Simultaneous CAF disruption reduces stromal fibrosis, facilitating anti–PD-L1 antibody delivery and T-cell infiltration. This dual-targeting strategy synergizes ICD with immune checkpoint blockade to eradicate bladder tumors by recruiting cytotoxic T cells and suppressing immunosuppressive phenotypes. Ex vivo studies in freshly resected human bladder tumors further validated the translational potential. Our findings highlight fluorinated albumin nanocages as a versatile transmucosal platform to remodel the tumor–stroma axis and amplify chemoimmunotherapy in bladder cancer.
研究领域:
肿瘤学
·
纳米医学
·
免疫治疗
·
药物递送
·
癌症生物学
✓ 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）