Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Jiulong Zhang,Xiaoyan Sun,Xiufeng Zhao,Chunrong Yang,Menghao Shi,Benzhuo Zhang,Haiyang Hu,Mingxi Qiao,Dawei Chen,Xiuli Zhao
Amplifying “eat me signal” during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary “eat me signal” for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe 2+ ) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d -ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H 2 O 2 concentration would induce hydroxyl radical (·OH) and oxygen (O 2 ) generation through Fenton reaction by Fe 2+ . DOX and ATP would be released from the amplifier, which could induce ICD effect and “ICD adjuvant” to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.
研究领域:
肿瘤学
·
免疫学
·
化疗
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yiyin Ruan,Huijie Han,Xin Guan,Weiwei Feng,Xiaojuan Cui
Among the three primary gynecological malignancies, ovarian cancer has the highest mortality rate, and its onset is often insidious. Despite standard treatments, relapse and drug resistance remain major challenges. Doxorubicin (DOX) is known to induce immunogenic cell death (ICD); however, some patients still experience tumor resistance and recurrence owing to tumor-driven immunosuppression. Indoleamine 2,3-dioxygenase (IDO), which is highly expressed in tumor tissues, impairs T-cell function and differentiation, thereby promoting immunosuppression. Consequently, combining the IDO inhibitor indoximod (IND) with DOX may reverse immunosuppression and enhance both T-cell–mediated and ICD-driven anticancer effects. However, both drugs are limited by high systemic toxicity and poor tumor targeting, necessitating the use of nanocarriers to improve delivery efficiency and minimize toxicity. This study aims to develop novel cell membrane–camouflaged liposomes capable of co-delivering IND and DOX (DOX/IND@cmLPs) for ovarian cancer therapy and to evaluate its anticancer effects in vitro and in vivo. The particle size of DOX/IND@cmLPs is measured as 111.7 ± 2.7 nm using a Malvern Zetasizer Pro, with a zeta potential of −22.4 ± 4.00 mV. Entrapment efficiency (EE) is assessed using ultra-high performance liquid chromatography and ultraviolet spectrophotometry, yielding EE values of 85.1% ± 3.4% for DOX and 23.9% ± 1.3% for IND. At both pH 7.4 and pH 5.5, DOX release from DOX/IND@cmLPs is rapid during the first 24 hours, followed by a slower, more sustained release. Coomassie Brilliant Blue staining and Western Blot analysis confirmed successful encapsulation of the cell membrane in the liposomes. The potent antitumor effect of DOX/IND@cmLPs is demonstrated via CellTiter-Glo assays in vitro. Flow cytometry and immunofluorescence staining revealed an increased ratio of CD8 + T cells to Treg cells in tumor tissues, suggesting that DOX/IND@cmLPs may partially reverse local tumor-induced immunosuppression. Reduced Ki-67 expression and increased TdT-mediated dUTP nick-end labeling positive cell ratios in tumor sections indicated that DOX/IND@cmLPs treatment suppressed tumor proliferation and promoted apoptosis. Immunohistochemistry showed alterations in mammalian target of rapamycin (mTOR)-related pathway proteins in tumors. Furthermore, DOX/IND@cmLPs could induce an abscopal effect and provide long-lasting tumor suppression in a subcutaneous mouse model. In this study, a formulation of DOX/IND-loaded liposomes camouflaged with ovarian cancer cell membranes is successfully developed, and their stable physicochemical properties are confirmed. As an effective nanodrug delivery system, DOX/IND@cmLPs exhibited enhanced tumor-targeting and immune-mediated anticancer activity both in vitro and in vivo, indicating their potential as a platform for future combined chemotherapy and immunotherapy.
研究领域:
纳米医学
·
癌症免疫治疗
·
药物递送系统
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制药纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Methods
·
2023
·Vol. 7
·期 5
·2300116
·
IF 12.4
Tiankuan Li,Zhongqian Hu,Feifei Song,Chenyao Wu,Qizeng Miao,Zhongmin Wang,Wei Feng,Jinhe Guo,Yu Chen
Photothermal immunotherapy, the combination of photothermal hyperthermia and immunotherapy, is a noninvasive and desirable therapeutic strategy to address the deficiency of traditional photothermal ablation for tumor treatment. However, insufficient T-cell activation following photothermal treatment is a bottleneck to achieve satisfactory therapeutic effectiveness. In this work, a multifunctional nanoplatform is rationally designed and engineered on the basis of polypyrrole-based magnetic nanomedicine modified by T-cell activators of anti-CD3 and anti-CD28 monoclonal antibodies, which have achieved robust near infrared laser-triggered photothermal ablation and long-lasting T-cell activation, realizing diagnostic imaging-guided immunosuppressive tumor microenvironment regulation following photothermal hyperthermia by reinvigorating tumor-infiltrating lymphocytes. By virtue of high-efficient immunogenic cell death and dendritic cell maturation combined with T-cell activation, this nanosystem markedly restrains primary and abscopal tumors as well as metastatic tumors with negligible side effects in vivo, exerting the specific function for suppressing tumor recurrence and metastasis by establishing a long-term memory immune response.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
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
Jiulong Zhang,Xiaoyan Sun,Xiufeng Zhao,Lin Liu,Xin Cheng,Chunrong Yang,Haiyang Hu,Mingxi Qiao,Dawei Chen,Xiuli Zhao
The tumor immunosuppressive microenvironment (TIM) greatly hindered the efficacy of cancer immunotherapy. Overexpressed indoleamine 2,3-dioxygenase-1 (IDO1) in tumor tissues plays a vital role in TIM generation, and downregulation of IDO1 expression may reverse TIM. Inspired by the Watson–Crick base-pairing rule, a versatile noncationic miRNA vector (miDAC@PDA) is developed for cancer immunotherapy. Doxorubicin (DOX), adenosine triphosphate (ATP), and copper ions (Cu2+) are coassembled into coordination polymer nanoparticles (DAC) and bind miRNA via the hydrogen bond interaction (miDAC) between adenine residues (ATP) and uracil residues (miRNA). Polydopamine (PDA) is deposited onto the surface of miDAC for photothermal therapy. miDAC@PDA can efficiently accumulate into tumor tissues for cellular uptake. Under laser irradiation and high intracellular GSH levels, the PDA shell of miDAC@PDA can dissociate from miDAC for miRNA release due to local hyperthermia. Cu2+-mediated GSH consumption and intracellular ATP release can amplify the DOX-based immunogenic cell death (ICD) cascade, together with miR-448-mediated IDO1 inhibition, and these versatile nanoplexes will not only restrain primary tumor growth but also display a remarkable abscopal effect on distant tumors. Collectively, our study provides a unique strategy for intracellular gene delivery and an inspirational approach for multimechanism cancer management.
研究领域:
癌症研究
·
纳米技术
·
治疗学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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