ACS Nano
·
2023
·
IF 17.1
Naihan Huang,Xiao-Yan Tang,Wei Meng,Ye-Hua Lai,Xuan Zhou,Xue-Zhao Yu,Wen-Hua Zhang,Jin-Xiang Chen
Due to the immunosuppressive tumor microenvironment (TME) and weak radiation absorption, the immune response triggered by radiation therapy (RT) is limited. Herein, a core–shell nanosensitizer UiO@MnS (denoted as UM) was genuinely constructed for the amplification of RT efficacy and induction of immunogenicity via integrating MnS-reprogrammed TME with Hf-based UiO-sensitized RT. The acid-sensitive MnS would produce H2S under acidic TME to improve oxygenation through inhibition mitochondrial respiration and reducing metabolic oxygen consumption, leading to decreased HIF-1α expression and enhanced radiosensitization. In addition, the generated H2S inhibited the catalase activity to increase the H2O2 level, which subsequently enhanced the Mn2+-mediated Fenton-like reaction, resulting in G2/M cell cycle arrest to improve the cellular sensitivity for radiation. This impressive tumor oxygenation, cell cycle arrest, and radiosensitization procedure boosted RT efficacy and resulted in strong antitumor immunogenicity. Taken together, combining the immunosuppressive TME modulation with a sensitizing radiation strategy shows great promise for magnifying immunogenic RT outputs.
研究领域:
癌症研究
·
纳米技术
·
放射肿瘤学
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免疫治疗
·
肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2023
·
IF 4.7
Jingsong Lu,Jing Yu,Wensheng Xie,Zhenhu Guo,Xiaohan Gao,Ying Li,Ziqing Zhang,Zeping Jin,Abdul Fahad,Shenglei Che,Lingyun Zhao,Yen Wei
Since the nonspecificity and nonselectivity of traditional treatment models lead to the difficulty of cancer treatment, nanobased strategies are needed to fill in the gaps of current approaches. Herein, a tumor microenvironment (TME)-responsive chemo-photothermal treatment model was developed based on dihydroartemisinin (DHA)-loaded conjugated polymers (DHA@PLGA-PANI). The synthesized DHA@PLGA-PANI exhibited enhanced photothermal properties under mild-acidic conditions and thus triggered local heat at the tumor site. Meanwhile, these iron-doped conjugated polymers of PLGA-PANI were used as the source of Fe, and benefiting from the Fe-dependent cytotoxicity of DHA, the burst of free radicals could be generated in tumors. Therefore, the combination of TME-responsive chemo-photothermal therapy could achieve effective tumor efficacy.
研究领域:
癌症治疗
·
纳米技术
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Jiayi Bian,Yingjie Xu,Minghao Sun,Zerui Ma,Hao Li,Changrui Sun,Fei Xiong,Xiaopeng Zhao,Wenjing Yao,Yue Chen,Yuanyuan Ma,Xikuang Yao,Shenghong Ju,Wenpei Fan
Accurate imaging and precise treatment are critical to controlling the progression of pancreatic cancer. However, current approaches for pancreatic cancer theranostics suffer from limitations in tumor specificity and invasive surgery. Herein, a pancreatic cancer-specific phototheranostic modulator (AuHQ) dominated by aggregation-induced emission (AIE) luminogens-tethered gold nanoparticles is meticulously designed to facilitate prominent fluorescence-photoacoustic bimodal imaging-guided photothermal immunotherapy. Once reaching the pancreatic tumor microenvironment (TME), the peptide Ala-Gly-Phe-Ser-Leu-Pro-Ala-Gly-Cys (AGFSLPAGC) linkage within AuHQ can be specifically cleaved by the overexpressed enzyme Cathepsin E (CTSE), triggering the dual self-assembly of AuNPs and AIE luminogens. The aggregation of AuNPs mediated by enzymatic cleavage results in potentiated photothermal therapy (PTT) under near-infrared (NIR) laser irradiation, induced immunogenic cell death (ICD), and enhanced photoacoustic imaging. Simultaneously, AIE luminogen aggregates formed by hydrophobic interaction can generate AIE fluorescence, enabling real-time and specific fluorescence imaging of pancreatic cancer. Furthermore, coadministration of an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with AuHQ can address the limitations of PTT efficacy imposed by the immunosuppressive TME and leverage the synergistic potential to activate systemic antitumor immunity. Thus, this well-designed phototheranostic modulator AuHQ facilitates the intelligent enzymatic dual self-assembly of imaging and therapeutic agents, providing an efficient and precise approach for pancreatic cancer theranostics.
研究领域:
生物医学工程
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癌症治疗
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纳米技术
·
成像科学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Guo Yiming,Wu Jicheng,Chen Lefan,Liu Lujie,Bi Tianxiang,Pan Yuanwei,Meng Qian-Fang,Wang Chaoliang,Rao Lang,Li Qi
Androgen deprivation therapy (ADT) is a crucial and effective strategy for prostate cancer, while systemic administration may cause profound side effects on normal tissues. More importantly, the ADT can easily lead to resistance by involving the activation of NF-κB signaling pathway and high infiltration of M2 macrophages in tumor microenvironment (TME). Herein, we developed a biomimetic nanotherapeutic platform by deriving cell membrane nanovesicles from cancer cells and probiotics to yield the hybrid cellular nanovesicles (hNVs), loading flutamide (Flu) into the resulting hNVs, and finally modifying the hNVs@Flu with Epigallocatechin-3-gallate (EGCG). In this nanotherapeutic platform, the hNVs significantly improved the accumulation of hNVs@Flu-EGCG in tumor sites and reprogramed immunosuppressive M2 macrophages into antitumorigenic M1 macrophages, the Flu acted on androgen receptors and inhibited tumor proliferation, and the EGCG promoted apoptosis of prostate cancer cells by inhibiting the NF-κB pathway, thus synergistically stimulating the antitumor immunity and reducing the side effects and resistance of ADT. In a prostate cancer mouse model, the hNVs@Flu-EGCG significantly extended the lifespan of mice with tumors and led to an 81.78% reduction in tumor growth compared with the untreated group. Overall, the hNVs@Flu-EGCG are safe, modifiable, and effective, thus offering a promising platform for effective therapeutics of prostate cancer. Graphical Abstract
研究领域:
癌症治疗
·
纳米技术
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免疫疗法
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Nannan Zheng,Yitong Chen,Lei Jiang,Hongchao Ma
Combined photo-induced cancer therapy (photothermal therapy (PTT) and photodynamic therapy (PDT)) is a promising anti-cancer strategy for its non-invasiveness property. However, severe hypoxia in tumor microenvironment (TME) would weaken the PDT effect and limit the clinical efficiency of PTT/PDT treatment. To solve this problem, denatured BSA-hemin-IR780 (dBHI) was designed and synthesized for anti-cancer treatment in this work. Denatured bovine serum albumin (dBSA) was used as the binding matrix to bind hemin and IR780 via covalent reaction and hydrophobic self-assembly, respectively. The obtained dBHI nanoparticles possess both PTT and PDT effect due to the presence of IR780 in the composites. Moreover, because of the existence of hemin, dBHI also exhibited photo-enhanced Fenton-like catalytic performance, which could decompose H 2 O 2 to form oxygen for improving the PDT effect and generate hydroxyl radical (·OH) for chemodynamic therapy (CDT). Therefore, by using dBHI, synergistic effect of PTT/PDT/CDT combined treatment has been achieved for cancer therapy.
研究领域:
癌症治疗
·
纳米技术
·
光疗
·
化学动力学治疗
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 5
·1317-1325
·
IF 7.59
Bengao Zhu,Xuefei Lv,Mengmeng Zhang,Huiying Wang,Senbin Chen,Jintao Zhu
Integrating magnetic resonance imaging (MRI)-targeted diagnosis with synergistic cascade treatments, such as chemo/chemodynamic therapy (CT/CDT), is highly desired for promoting the antitumor performance; however, the rational design of such “all-in-one” nanomedicine is still in its infancy. In this report, using MnO2 coated layered dihydroxide (LDH) as a carrier to load chemotherapy molecule 5-flurouracil (5-FU), a novel tumor microenvironment (TME) regulating nanodrug is formed: LDH/5-FU@MnO2. Combined guidance of CT/CDT and MRI is used to realize synergistic diagnosis and enhanced anti-tumor efficacy. MnO2 is converted into Mn2+ in the presence of reducing agent GSH, the in situ generated Mn2+, not only serves as the chemical fuel for the Fenton reaction, combining H2O2 depletion and ˙OH generation, but can also be used as a nuclear magnetic contrast agent for MRI. Moreover, the tumor acidic environment is able to trigger 5-FU release for initiating chemotherapy in the tumor zone. This “all-in-one” LDH/5-FU@MnO2 nanomedicine integrating multiple treatment modalities and magnetic resonance imaging properties, causes persistent modulation of the TME and exhibits effective antitumor theranostic performance. Such a sophisticated nanomedicine design not only achieves improved CT/CDT antitumor efficiency, but also realizes the activatable magnetic resonance imaging. This strategy combines the merits of each treatment, significantly enhancing the anticancer efficacy, and is anticipated to display promising potentials in the clinical translation plans.
研究领域:
纳米技术
·
癌症治疗
·
医学影像
·
药学科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 22
·7456-7470
·
IF 6.843
Xiangyu Meng,Jia Song,Yunfeng Lei,Xuezhong Zhang,Zhixin Chen,Zhuoxuan Lu,Liming Zhang,Zhifei Wang
Severe hypoxia in solid tumors limits the efficacy of oxygen (O2)-dependent photodynamic therapy (PDT). The overexpressed heat shock proteins (HSPs) in tumor cells hamper the effect of photothermal therapy (PTT). Herein, a tumor oxygenation-enhanced and ATP-reduced gelatin nanoreactor (MCGPD ∼ RGD NPs) for PDT/PTT-augmented combination cancer therapy is reported. In this nanosystem, the Arg-Gly-Asp (RGD) peptides of MCGPD ∼ RGD NPs can ensure accurate recognition and sufficient accumulation in the tumor site. After accumulation, doxorubicin (DOX) can be released from MCGPD ∼ RGD NPs in a mild acidic tumor microenvironment (TME) for highly efficient chemotherapy. Upon 808 nm laser irradiation, the overexpressed matrix metalloproteinase-2 (MMP-2) in the TME and the heat produced from the PDA coating trigger Gel NP degradation to expose chlorin e6 (Ce6) and Met from the cavity of MCGPD ∼ RGD NPs. The exposed Met elevates the O2 content and reduces ATP production in tumor sites to spur the successful O2-dependent PDT and HSP-mediated PTT. The heat generated by the PDA coating directly kills the tumor cells to ensure PTT and amplifies the chemotherapeutic effect. In vitro and in vivo assays indicate that MCGPD ∼ RGD NPs have excellent ability to promote cell apoptosis and to inhibit tumor growth. Overall, this smart responsive hydrogel nanosystem with hypoxia-relieving capacity and ATP-decreasing performance provides a promising strategy against cancer.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 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
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Guoting Su,Hui Xu,FangFang Zhou,Xiyu Gong,Songwen Tan,Yongju He
Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO2 and dihydroartemisinin (DHA) (LIPSe@CuO2&DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO2 and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H2O2 and Cu2+, CuO2 can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu2+ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H2O2 and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu2+ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu2+-to-Cu+ conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO2&DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.
研究领域:
纳米医学
·
癌症治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Qianqian Qiao,Zerui Liu,Fei Hu,Ziqiang Xu,Ying Kuang,Cao Li
Catalytic medicine, using enzymes or nanozymes, is an emerging method for cancer treatment. However, its applicability is limited by the low catalytic activity in the tumor microenvironment (TME). In this work, a versatile and synthesis-friendly nanozyme, CeO 2 Mn 1.08 O x nanoclusters, is prepared. This novel Ce─Mn heterojunction is formed by oxidation of CeO 2 nanoparticles through H 2 SO 4 /KMnO 4 . CeO 2 Mn 1.08 O x exhibits high multi-enzymatic catalytic activities and acts as a catalase (CAT), peroxidase (POD), and oxidase (OXD) mimics under acidic conditions. It can regulate the TME by relieving hypoxia and consuming endogenous glutathione (GSH). Glucose oxidase (GOx) is then incorporated into CeO 2 Mn 1.08 O x and linked with poly(ethylene glycol) (PEG) to obtain the cascade enzyme system (Ce─Mn)-PEI/GOx-PEG. CeO 2 Mn 1.08 O x exhibits CAT-like properties, which sensitize GOx-based starvation therapy, and POD- and OXD-like properties, which generate highly cytotoxic reactive oxygen species (ROS) in cancer cells. The glucose catabolic product, H 2 O 2 , is also used to generate O 2 and ROS. In addition, the heterojunction structure provides CeO 2 Mn 1.08 O x with near-infrared (NIR) photothermal capability, making it suitable for photothermal therapy (PTT). Density functional theory (DFT) calculations provide possible reasons for the high catalytic activity and photothermal capability of CeO 2 Mn 1.08 O x . When combining mild PTT with catalytic therapy, the cascade enzyme system (Ce─Mn)-PEI/GOx-PEG can efficiently ablate tumors.
研究领域:
癌症研究
·
纳米技术
·
生物医学工程
·
诊疗学
·
材料科学
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Haoyu Chen,Minjuan Wang,Qiquan Yang,Jing Liu,Feng Liu,Xiaohua Zhu,Shu Huang,Peng Yin,Xingfeng Wang,Haitao Li,Youyu Zhang,Meiling Liu,Mingjie Wei,Shouzhuo Yao,Yang Liu
The integration of reactive oxygen species (ROS) related photodynamic therapy (PDT) with the strategy of reshaping the tumor microenvironment (TME) has emerged as a potential approach for nanodiagnostic and therapeutic interventions. However, the therapeutic efficacy based on ROS treatments may be hindered by intracellular antioxidants such as glutathione (GSH) and tumor hypoxia. To address these challenges, a nanoplatform based on GSH-responsive multifunctional porphyrinic metal–organic framework (PCN-224@Au@MnO 2 @HA, PAMH) was proposed. It was developed through a layer-by-layer in-situ growth method. This method avoids the need for high-temperature calcination and complex modification processes while improving the stability of PCN-224 in a phosphate-rich environment. GSH depletion leads to oxidation–reduction imbalance in TME. With the inactivation of GSH peroxidase 4 (GPX4), the content of hydrogen peroxide (H 2 O 2 ) increases, ultimately triggering lipid peroxidation (LPO) and promoting ferroptosis. The catalase-like activity of Au nanozymes facilitates the generation of oxygen (O 2 ), thereby mitigating tumor hypoxia and downregulating hypoxia-inducing factors (HIF-1α). Due to the presence of porphyrin ligands in PCN-224, the generated O 2 can be further converted to toxic singlet oxygen ( 1 O 2 ) under laser irradiation. Additionally, the platform allows near-infrared (NIR) fluorescence imaging, providing real-time information on intracellular GSH changes during PDT and ferroptosis. The PAMH nanoplatform has shown effective inhibition of tumor growth in subcutaneous models via both intravenous and intratumoral injection, indicating its potential in modulating reactive oxygen/sulfur species and reshaping TME, thereby facilitating imaging-guided cascaded nanocatalytic therapy.
研究领域:
纳米医学
·
癌症治疗
·
生物化学
·
材料科学
·
成像技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Qingle Song,Guofang Zhang,Bo Wang,Guoli Cao,Dongjie Li,Yu Wang,Yuqian Zhang,Jin Geng,Hongchang Li,Yang Li
Although immuno-oncotherapy in clinic has gained great success, the immunosuppressive tumor microenvironment (TME) existing in the “cold” tumor with insufficient and exhausted lymphocytes may result in a lower-than-expected therapeutic efficiency. Therefore, a properly designed synergistic strategy that can effectively turn the “cold” tumor to “hot” should be considered to improve the therapeutic effects of immuno-oncotherapy. Herein, TME-responsive penetrating nanogels (NGs) were developed, which can improve the delivery and penetration of the co-loaded resiquimod (R848) and green tea catechin (EGCG) in tumors by a nano-sized controlled releasing system of the soluble cyclodextrin-drug inclusion complex. Consequently, the NGs effectively promoted the maturation of dendritic cells, stimulated the cytotoxic T lymphocytes (CTLs), and decreased the PD-L1 expression in tumors. The combination of NGs with the OX40 agonist (αOX40) further synergistically enhanced the activation and infiltration of CTLs into the deep tumor and inhibited the suppression effects from the regulatory T cells (Tregs). As a result, an increased ratio of active CTLs to Tregs in tumors (20.66-fold) was achieved with a 91.56% tumor suppression effect, indicating a successful switch of “cold” tumors to “hot” for an immunologically beneficial TME with significantly improved anti-tumor immune therapeutics. This strategy could be tailored to other immuno-oncotherapeutic approaches to solve the urgent efficiency concerns of the checkpoint-based treatment in clinic.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）