Nanoscale
·
2021
·Vol. 13
·期 29
·12553-12564
·
IF 7.79
Hai-Yan Wang,Zheng-Chen Su,Xi-Wen He,Wen-You Li,Yu-Kui Zhang
Chemodynamic therapy (CDT), the ability to transform H2O2 into a highly toxic hydroxyl radical (˙OH) through a Fenton or Fenton like reaction to kill cancer cells, enables selective tumor therapy. However, the effect is seriously limited by the insufficiency of endogenous H2O2 in cancer cells. Additionally, the specific recognition of epitope imprinting plays an important role in targeting cancer cell markers. In this work, we prepared H2O2 self-supplying degradable epitope molecularly imprinted polymers (MIP) for effective CDT, employing fluorescent calcium peroxide (FCaO2) as an imaging probe and a source of H2O2, the exposed peptide in the CD47 extracellular region as the template, copper acrylate as one of the functional monomers and N,N‘-bisacrylylcystamine (BAC) as a cross-linker. MIP with recognition sites can specifically target CD47-positive cancer cells to achieve fluorescence imaging. Under the reduction of glutathione (GSH), the MIP were degraded and the exposed FCaO2 reacted with water to continuously produce H2O2 in the slightly acidic environment in cancer cells. The self-supplied H2O2 produced ˙OH through a Fenton like catalytic reaction mediated by copper ions in the MIP framework, inducing cancer cell apoptosis. Therefore, the MIP nano-platform, which was capable of specific recognition of the cancer cell marker, H2O2 self-supply and controlled treatment, was successfully used for targeted CDT.
研究领域:
癌症治疗
·
材料科学
·
生物医学工程
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Ying-Ying Guan,Shao-Qi Zeng,Yin Qin,Yan Mu,Hong Liu
To overcome cancer drug resistance and to reverse tumor immunosuppression, a vitamin E-tocopheryl polyethylene glycol succinate (TPGS) decorated polymer-based drug delivery system was developed. The effects of the drug delivery system on diverse proteins involved in cell apoptosis, cancer invasion, metastasis and immunosuppression were investigated to provides a more comprehensive understanding of TPGS modified drug delivery systems. Curcumin (CUR), a hydrophobic drug, was loaded in star poly(DL-lactide) with a cholic acid core, and then decorated with TPGS shell to obtain [email protected] /star poly(DL-lactide) nanoparticles ( [email protected] ). Cholic acid cored star poly(DL-lactide) is featured by a rapid degradation rate with a surface erosion characteristic. TPGS not only reverses tumor drug resistance through downregulating P-gp expression of tumor cells but also enhances the anti-tumor efficiency through combined TPGS/CUR therapeutic actions on reversal of tumor immunosuppression mediated by CD47 and PD-L1. As compared with the CUR loaded nanoparticles without TPGS decoration, [email protected] with TPGS decoration results in significantly enhanced intracellular drug accumulation to efficiently induce cell apoptosis in drug resistant tumor cells. More importantly, [email protected] possesses considerably improved efficacy in upregulating p53 and p21 as well as downregulating β-catenin, MMP-9, Snail, CD47 and PD-L1, indicating the TPGS decorated drug delivery system inhibits tumor development and metastasis much more efficiently.
研究领域:
药学
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肿瘤学
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药物递送系统
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免疫治疗
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Mengmeng Xiong,Ying Zhang,Huan Zhang,Qiaoqiao Shao,Qifan Hu,Junjie Ma,Yiqun Wan,Lan Guo,Xin Wan,Haitao Sun,Zhongyi Yuan,Hao Wan
Aggressive nature of colon cancer and current imprecise therapeutic scenarios simulate the development of precise and effective treatment strategies. To achieve this, a tumor environment-activated photosensitized biomimetic nanoplatform (PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM) is fabricated by encapsulating metal-organic framework loaded with developed photosensitizer PEG 2000 -SiNcTI-Ph and immunoadjuvant CpG oligodeoxynucleotide within fusion cell membrane expressing programmed death protein 1 (PD-1) and cluster of differentiation 47 (CD47). By stumbling across, systematic evaluation, and deciphering with quantum chemical calculations, a unique attribute of tumor environment (low pH plus high concentrations of adenosine 5′-triphosphate (ATP))-activated photodynamic effect sensitized by long-wavelength photons is validated for PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM, advancing the precision of cancer therapy. Moreover, PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM evades immune surveillance to target CT26 colon tumors in mice mediated by CD47/signal regulatory proteins α (SIRPα) interaction and PD-1/programmed death ligand 1 (PD-L1) interaction, respectively. Tumor environment-activated photodynamic therapy realized by PEG 2000 -SiNcTI-Ph/CpG-ZIF-8@CM induces immunogenic cell death (ICD) to elicit anti-tumor immune response, which is empowered by enhanced dendritic cells (DC) uptake of CpG and PD-L1 blockade contributed by the nanoplatform. The photodynamic immunotherapy efficiently combats primary and distant CT26 tumors, and additionally generates immune memory to inhibit tumor recurrence and metastasis. The nanoplatform developed here provides insights for the development of precise cancer therapeutic strategies.
研究领域:
肿瘤学
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生物医学工程
·
纳米技术
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免疫学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Liuwei Zhang,Jingyun Wang,Hongyan Cui,Haonan Zheng,Xiaolan Yin,Jiaqi Lin,Yue Wang,Yan Zhao,Haidong Li,Qixian Chen
Tumors managing to exempt from immune clearance are attributable to their overexpressed immune suppressive molecules (CD47, PD-L1, etc.). Leadingly, the checkpoint blockade-based chemoimmunotherapy by means of knockdown of these immunosuppressive checkpoints, together with immunogenetic chemotherapeutics, is perceived to be a valid therapeutic strategy for improving anti-tumor outcomes. Herein, chemotherapeutic camptothecin was covalently introduced into an intriguing multifaceted nanomedicine. Note that the elaborated nanomedicine was chemically engineered to enable targeted transportation to the tumors via systemic administration, possessing intelligent responsiveness to sequential extracellular and intracellular microenvironments in the targeted tumors for prompted transcellular endocytosis owing to enzymolysis by the tumor-enriched matrix metalloproteinases and the selective liberation of cytocidal camptothecin in the cell interiors owing to thiolysis by glutathione. In addition, this chemotherapeutic nanomedicine allowed facile encapsulation of the negatively charged RNA interference payloads. Consequently, aiming for treatment of intractable triple-negative breast tumors, we attempted the small interfering RNA (siRNA) payloads aiming for CD47 and PD-L1 into the aforementioned nanomedicine. The subsequent investigations demonstrated drastic knockdown of these vital immune suppressive checkpoints by this siRNA-encapsulating chemotherapeutic nanomedicine, conducing to the reversal of the immune checkpoint suppressive microenvironment of triple-negative 4T1 tumors. Namely, the inhibited proceedings of the innate and adaptive anti-tumor immunities were revived, as supported by observation of the activated infiltration and retention of CD68+ macrophages and CD4+ and CD8+ lymphocytes into the tumors. Eventually, most potent anti-tumor efficacies were accomplished by systemic administration of this chemoimmunotherapeutic nanomedicine, which verified the amplified contribution from anti-tumor immunities by means of knockdown of the immune suppressive molecules to the ultimate anti-tumor efficacies. Note that the upregulation of the immune suppressive molecules was constantly reported in a variety of clinical therapies; hence, our facile chemoimmunotherapeutic platform should be emphasized in clinical translation for seeking improved therapeutic outcomes.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
免疫学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Jun-Long Liang,Xiao-Kang Jin,Guo-Feng Luo,Shi-Man Zhang,Qian-Xiao Huang,Yan-Tong Lin,Xin-Chen Deng,Jia-Wei Wang,Wei-Hai Chen,Xian-Zheng Zhang
Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, “eat me” signal calreticulin (CRT) was upregulated, while the “don’t eat me” signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8+ T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.
研究领域:
生物医学工程
·
癌症免疫疗法
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药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Yingying Zhang,Hongbin Chen,Hanjie Wang,Tiange Wang,Huizhuo Pan,Wanying Ji,Jin Chang
Immunotherapy has become a promising therapy in cancer treatment. Both photothermal therapy (PTT) and genotoxic chemotherapy can trigger immune responses. On this subject, a synergistic cancer immunotherapy nano-system was developed for treating primary and distant tumors. This long-time, synergistic therapeutic system consisted of two parts: one was indocyanine green (ICG) and sepantronium bromide (YM155) co-loaded mesoporous silica nanoparticles (MSNs) for PTT and genotoxic chemotherapy, which could effectively destroy primary tumors and thus cause exposure of tumor antigens for cancer immunotherapy. The other was silica nanoparticles (nSiO 2 ) coated with magnetic nanoparticles (MNP) and conjugated with anti-CD47 antibody (anti-CD47), which demonstrated a strong antitumor immune effect of distant tumors after PTT and genotoxic chemotherapy. In vitro and vivo results proved that this synergistic system could efficiently inhibit primary and distant tumor growth. We expected that this paper may develop a promising strategy to prevent tumor growth for basic and clinical research.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Lili Cheng,Peng Zhang,Yadong Liu,Zhuoyin Liu,Junjie Tang,Langtao Xu,Jie Liu
Due to the immunosuppressive tumor microenvironment (ITM) resulting from tumor-associated macrophages (TAMs) and regulatory T cells, immune checkpoint blockade and vaccine therapies often lead to an inadequate immune response. Recently, cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING)-mediated innate immunity has emerged as a promising cancer therapeutic, as STING pathway activation could promote dendritic cells (DCs) maturation and tumor-specific cytotoxic T lymphocyte (CTL) and natural killer (NK) cell infiltration. Herein, multifunctional hybrid exosomes for cGAS/STING activation are designed by fusing genetically engineered exosomes carrying CD47 derived from tumor cells with exosomes from M1 macrophages, which are further encapsulated with DNA-targeting agent (SN38) and STING-agonist (MnO 2 ). The hybrid exosomes demonstrate great tumor-targeting capacity and prolong blood circulation time due to the surface decoration of CD47. At the tumor site, the hybrid exosomes induce TAMs polarization to the M1 phenotype and release SN38 to induce DNA damage and Mn 2+ to stimulate cGAS/STING activation. Furthermore, the resulting multifunctional hybrid exosomes (SN/Mn@gHE) promote DCs maturation and facilitate CTL infiltration and NK cell recruitment to the tumor region, leading to significant anti-tumor and antimetastatic efficacy. Our study suggests a novel strategy to enhance cancer immunotherapy by activating the STING pathway and ameliorating ITM.
研究领域:
癌症生物学
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免疫学
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药学
·
纳米技术
✓ 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）