ACS Applied Nano Materials
·
2024
·
IF 5.3
Ge Sun,Yubiao Huang,Xiaoyu Cheng,Lijun Fang,Chunling Wang,Yinlong Zhang
Anlotinib, a multitargeted tyrosine kinase inhibitor (TKI) with a dual effect of inhibiting both tumor angiogenesis and tumor cell proliferation, holds great promise in cancer therapy. However, its clinical application has been limited due to off-target side effects. With the rapid development of drug delivery systems, there is increasing potential to improve therapeutic efficacy while reducing the toxicity associated with free drugs. Among these, liposomes stand out due to their excellent biocompatibility, and several liposomal drug formulations have been approved by the U.S. Food and Drug Administration (FDA). In this study, we prepared anlotinib-loaded liposomes (designated as Lipo-Anlotinib) using the ammonium sulfate gradient method, aiming to enhance its clinical applicability through a more efficient delivery system. The antitumor activity of Lipo-Anlotinib was evaluated in vitro against three cell lines (A549, 4T1, and CT26). Additionally, Lipo-Anlotinib exhibited improved therapeutic efficacy over free anlotinib in a 4T1 subcutaneous tumor model. Serum biochemical analysis and histological examination revealed that Lipo-Anlotinib exhibited reduced toxicity in comparison to free anlotinib. This liposomal formulation offers a promising approach to enhancing the antitumor efficacy while mitigating the side effects of anlotinib.
研究领域:
药理学
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肿瘤学
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纳米技术
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生物医学工程
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癌症治疗
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产品关联
DOI
高影响因子
Cell Death & Disease
·
2023
·Vol. 14
·期 2
·1-11
·
IF 9
Yao Yuan,Feng Suya,Li Xuejiao,Liu Taohua,Ye Shengying,Ma Long,Man Shuli
Litchi chinensis seed, as a valuable by-product of the subtropical fruit litchi ( Litchi chinensis Sonn.), has been confirmed to be rich in procyanidins (LPC). The anticarcinogenic properties of procyanidins has been primarily attributed to their antioxidant and anti-inflammatory activities. However, there is a comparative paucity of information on if and how LPC inhibits colon cancer. Here, LPC significantly inhibited CT26 colon cancer cells proliferation and metastasis in vivo and in vitro. In CT26 lung metastatic mice, the anti-metastatic effect of LPC relied on its regulation of gut microbiota such as increase of Lachnospiraceae UCG-006, Ruminococcus , and their metabolites such as acetic acid, propionic acid and butyric acid. In addition, LPC significantly inhibited CT26 colon cancer cells metastasis through increasing CD8 + cytotoxic T lymphocytes infiltration and decreasing the number of macrophages. Antibiotics treatment demonstrated that the therapeutic effect of LPC depended on the gut microbiota, which regulated T cells immune response. Taken together, LPC had strong inhibitory effects on colon cancer pulmonary metastasis by triggering gut-lung axis to influence the T cells immune response. Our research provides a novel finding for the utilization of procyanidins in the future, that is, supplementing more fruits and vegetables rich in procyanidins is beneficial to the treatment of colon cancer, or it can be used as an adjuvant drug in clinical anti-tumor immunotherapy.
研究领域:
肿瘤学
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免疫学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Siyu Li,Zhaorong Ouyang,Mengjie Zhang,Shuai Guo,Biao Cai,Houli Liu
Selenomethionine (SeM) holds great potential applications in tumor therapy. However, the tumor-targeting ability of SeM in vivo remains challenging. Herein, we utilize extracellular vesicles (EV) as tumor-targeted drug delivery systems to achieve enhanced specific targeting and antitumor efficacy. The carboxyl groups of SeM are conjugated with the amino groups of EV derived from low-pH culture medium reprogrammed CT26 cells (LEV) to obtain the SeM-based formulations (SMLEV), which can actively target tumor cells and enhance uptake efficacy through specific behaviors of LEV to their parent cells. Mechanistic studies indicate that SMLEV can induce reactive oxygen species (ROS) overproduction, mitochondrial dysfunction, as well as Caspase-9 and Caspase-3 activation. Here, SMLEV exhibit enhanced cytotoxic potential toward colon tumor (CT26) cells. After systemic administration, the growth of tumors is inhibited in vivo using CT26 tumor-bearing mice. Our findings can provide insights and a strategy in developing SeM delivery for tumor treatment.
研究领域:
肿瘤学
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药学
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生物技术
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产品关联
DOI
高影响因子
CANCER LETTERS
·
2020
·
IF 7.36
Huimin Tao,Lu Cheng,Lihua Liu,Hong Wang,Zhijie Jiang,Xu Qiang,Lijun Xing,Yifeng Xu,Xinying Cai,Jing Yao,Min Wang,Zheng Qiu
Antibodies blocking the PD-1/PD-L1 pathway have achieved great success. However, some disadvantages of antibodies have been found, which limit their clinical applications. Peptide antagonists are alternatives to antibodies in PD-1/PD-L1 blockage, but successful studies in this area are limited. A PD-1 targeting peptide, P–F4, was identified using phage display. P–F4 bound PD-1 with an affinity of 0.119 μM, inhibited PD-1/PD-L1 interaction at the cellular level and modulated T cell activity in vitro . We have overcome the poor solubility and rapid degradation problems of this peptide by packaging P–F4 in nanoparticles. In vivo experiments demonstrated that P–F4 nanoparticles could strongly inhibit tumor growth in a CT26 mouse model. Further research revealed that treatment of P–F4 nanoparticles increased CD8+T cells and reduced Tregs in the tumor microenvironment and tumor-draining lymph nodes. It was shown that treatment of P–F4 nanoparticles also increased lymphocytic activities, including proliferation, cytokine secretion and cytolytic activity. Moreover, computer modeling suggested that the P–F4 binding site to PD-1 overlaps with the PD-L1 binding surface. In this study, a peptide candidate for cancer immunotherapy was provided, and its working mechanisms were studied.
研究领域:
癌症免疫疗法
·
药学
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免疫学
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生物技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Yuan-Fu Ding,Xun Xu,Junyan Li,Ziyi Wang,Jingwei Luo,Greta S.P. Mok,Shengke Li,Ruibing Wang
Dual- or multi-modality combination therapy has become one of the most effective strategies to overcome drug resistance in cancer therapy, and the optimized ratio of the therapeutic agents working on the tumor greatly affects the therapeutic outcomes. However, the absence of a facile method to optimize the ratio of therapeutic agents in nanomedicine has, at least in part, impaired the clinical potential of combination therapy. Herein, a new cucurbit[7]uril (CB[7])-conjugated hyaluronic acid (HA) based nanomedicine was developed, in which both chlorin e6 (Ce6) and oxaliplatin (OX) were co-loaded non-covalently at an optimized ratio via facile host-guest complexation, for optimal, combined photodynamic therapy (PDT)/chemotherapy. To maximize the therapeutic efficacy, a mitochondrial respiration inhibitor, atovaquone (Ato), was also loaded into the nanomedicine to limit consumption of oxygen by the solid tumor, sparing oxygen for more efficient PDT. Additionally, HA on the surface of nanomedicine allowed targeted delivery to cancer cells with over-expressed CD44 receptors (such as CT26 cell lines). Thus, this supramolecular nanomedicine platform with an optimal ratio of photosensitizer and chemotherapeutic agent not only provides an important new tool for enhanced PDT/chemotherapy of solid tumors, but also offers a CB[7]-based host-guest complexation strategy to facilely optimize the ratio of therapeutic agents for multi-modality nanomedicine. Statement of significance Chemotherapy remains the most common modality for cancer treatment in clinical practice. Combination therapy by co-delivery of two or more therapeutic agents has been recognized as one of the most effective strategies to improve therapeutic outcome of cancer treatment. However, the ratio of loaded drugs could not be facilely optimized, which may greatly affect the combination efficiency and overall therapeutic outcome. Herein, we developed a hyaluronic acid based supramolecular nanomedicine with facile method to optimize the ratio of two therapeutic agents for improved therapeutic outcome. This supramolecular nanomedicine not only provides an important new tool for enhanced photodynamic therapy/chemotherapy of solid tumors, but also offers insights in using macrocyclic molecule-based host-guest complexation to facilely optimize the ratio of therapeutic agents in multi-modality nanomedicine.
研究领域:
纳米技术
·
药学
·
肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
·
免疫学
·
药学
·
生物技术
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·
IF 29.4
Yucai Zhang,Heon Gyu Kang,Hua-zhen Xu,Honghui Luo,Minoru Suzuki,Qing Lan,Xiao Chen,Naoki Komatsu,Li Zhao
Boron neutron capture therapy (BNCT) has emerged as a treatment modality with high precision and efficacy of intractable tumors. At the core of effective tumor BNCT are 10 B carriers with facile preparation as well as advantageous pharmacokinetic and therapeutic profiles. We herein report the design and preparation of sub-10 nm 10 B-enriched hexagonal boron nitride nanoparticles grafted with poly(glycerol) (h- 10 BN-PG), and their application to cancer treatment by BNCT. By virtue of their small particle size and outstanding stealth property, h- 10 BN-PG nanoparticles accumulate efficiently in murine CT26 colon tumors with a high intratumor 10 B concentration of 8.8%ID/g or 102.1 μg/g at 12 h post-injection. Moreover, h- 10 BN-PG nanoparticles penetrate into the inside of the tumor parenchyma and then are taken up by the tumor cells. BNCT comprising a single bolus injection of h- 10 BN-PG nanoparticles and subsequent one-time neutron irradiation results in significant shrinkage of subcutaneous CT26 tumors. h- 10 BN-PG-mediated BNCT not only causes direct DNA damage to the tumor cells, but also triggers pronounced inflammatory immune response in the tumor tissues, which contributes to long-lasting tumor suppression after the neutron irradiation. Thus, the h- 10 BN-PG nanoparticles are promising BNCT agents to eradicate tumor through highly efficient 10 B accumulation. This article is protected by copyright. All rights reserved
研究领域:
癌症研究
·
纳米技术
·
治疗放射学
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免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2022
·
IF 14.026
Min Mu,Xiaoyan Liang,Na Zhao,Di Chuan,Bo Chen,Shasha Zhao,Guoqing Wang,Rangrang Fan,Bingwen Zou,Bo Han,Gang Guo
Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer; hence, new and efficient strategies are necessary. In this study, a supramolecular nanoreactor ( [email protected] 3+ ) based on tannic acid (TA), iron ion (Fe 3+ ), and docetaxel (DOC) with microtubule inhibition, reactive oxygen species (ROS) generation, and glutathione peroxidase 4 (GPX4) inhibition, is prepared for ferroptosis/apoptosis treatment. After internalization by CT26 cells, the [email protected] 3+ nanoreactor escapes from the lysosomes to release payloads. The subsequent Fe 3+ /Fe 2+ conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration. Additionally, Fe 3+ can consume glutathione to repress the activity of GPX4 to induce ferroptosis. Meanwhile, the released DOC controls microtubule dynamics to activate the apoptosis pathway. The superior in vivo antitumor efficacy of [email protected] 3+ nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model. Therefore, the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Lifeng Luo,Baoli Zhang,Feng Tao,Zhong Chen,Qingsong Ye,Xiaozhi Zhao,Jinhui Wu
Tumor metastasis contributes to the low overall survival of tumor patients, while transforming growth factor-β (TGFβ) has been recognized as a prominently promoting factor in the development of tumor metastasis. Platelets reserve abundant TGFβ, which will be secreted to peripheral blood after activation, and they are the dominant source of circulating TGFβ. Therefore, downregulation of platelet-derived TGFβ is expected to inhibit the metastasis of circulating tumor cells. Here, unfolded human serum albumin (HSA)-coated perfluorotributylamine (PFTBA) nanoparticles were constructed to display a favorable platelet delivery and an antiplatelet effect to downregulate platelet-derived TGFβ in vitro and in blood plasma. PFTBA@HSA-mediated TGFβ downregulation impaired epithelial-mesenchymal transition of tumor cells as well as their migration and invasion behaviors and enhanced immune surveillance of NK cells. Intravenous injection of PFTBA@HSA effectively reduced tumor metastasis on the lungs or liver to improve the survival rate of mice on multiple metastatic models, including CT26 colon cancer, B16F10 melanoma, and 4T1 breast cancer. Compared with the clinical antiplatelet drug ticagrelor, PFTBA@HSA reduced bleeding risk when displaying a favorable downregulation on platelet-derived TGFβ, thereby obtaining a higher therapy benefit. Together, this study confirmed that downregulation of platelet-derived TGFβ by PFTBA@HSA will be a potential approach and therapeutic candidate for the prevention of tumor metastasis.
研究领域:
肿瘤学
·
药理学
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纳米技术
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Mengshi Jiang,Bing Qin,Lihua Luo,Xiang Li,Yingying Shi,Junlei Zhang,Zhenyu Luo,Chunqi Zhu,Guannan Guan,Yongzhong Du,Jian You
The hypoxic tumor microenvironment (TME) hinders the effectiveness of immunotherapy . Alleviating tumor hypoxia to improve the efficacy of immune checkpoint inhibitors (ICIs) represented by programmed cell death protein 1 (PD-1) antibody has become a meaningful strategy. In this study, we adopted three methods to alleviate hypoxia, including direct oxygen delivery using two different carriers and an indirect way involving HIF-1α inhibition. Both in vivo and in vitro experiments showed that liposomes modified with perfluorocarbon or hemoglobin ( [email protected] or [email protected] ) were able to efficiently load and release oxygen, relieving tumor hypoxia. However, the gas release behavior of [email protected] was uncontrollable, which might induce acute hyperoxia side effects during intravenous injection and reduce its biosafety. In contrast, whether administered locally or systemically, [email protected] revealed high animal tolerance, and was much safer than commercial HIF-1α inhibitor (PX-478), displaying prospects as a promising oxygen carrier for clinical practice. Pharmacodynamic experiments suggested that [email protected] helped PD-1 antibody break the therapeutic bottleneck and significantly inhibited the progression of 4 T1 breast cancer. But in CT26 colon cancer , the combination therapy failed to suppress tumor growth. After in-depth analysis and comparison, we found that the ratio of M1/M2 tumor associated macrophages (TAMs) between these two tumor models were dramatically different. And the lower M1/M2 ratio in CT26 tumors limited the anti-tumor effect of combination therapy. In this study, three methods for alleviating tumor hypoxia were compared from the perspectives of biosafety, efficacy and clinical applicability. Among them, [email protected] stood out, and its combined use with PD-1 antibody exhibit a distinct synergistic suppression effect on tumors with more M1 macrophages presented in the microenvironment. Our work provided a good reference for improving the efficacy of PD-1 antibody by alleviating tumor hypoxia.
研究领域:
肿瘤学
·
免疫疗法
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Yunjian Yu,Jie Li,Boyi Song,Zhuang Ma,Yufei Zhang,Haonan Sun,Xiaosong Wei,Yayun Bai,Xueguang Lu,Peng Zhang,Xinge Zhang
Checkpoint inhibitors, such as antibodies blocking the PD-1/PD-L1 pathway, are among the most promising immunotherapies to treat metastatic cancers, but their response rate remains low. In addition, the usage of monoclonal antibodies as checkpoint inhibitors is associated with a series of drawbacks. Herein, an all synthetic nanoparticle with PD-L1 blockade capability is developed for cancer photothermal-immunotherapy. The polymeric nanoparticle integrates photothermal treatment, antitumor vaccination, and PD-1/PD-L1 blockade in a single system to augment the antitumor efficacy. In a CT26 bilateral tumor model, intravenously injected nanoparticles accumulate in tumor sites and mediate strong photothermal effects, eradicate the NIR treated primary tumors and elicit strong antitumor immunity by inducing immunogenic cell death (ICD). Growth of the untreated distant tumors is also suppressed due to the synergies of systemic antitumor immune activation and PD-L1 blockade. Our strategy offers a simple but promising approach for the treatment of metastatic cancer.
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
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Chaofan Nie,Tao Feng,Peiren Wang,Xueqing Jiang,Pandi Peng,Xue Yang,Junru Wang,Luofeng Yu,Yuxin Guo,Peng Li
Conventional anti-tumor methods face challenges such as limited targetability and severe side effects, even when using carrier-assisted delivery of corresponding agents. Additionally, relying on a single modality often leads to an inadequate treatment response. Leveraging the facultative bacteria’s migration tendency to hypoxic tumor tissue and the effectiveness of physicochemical approaches in bacterial engineering, non-pathogenic Escherichia coli MG1655 was metabolically modified for tumor-targeted and synergistic therapy. By taking advantage of the essential D-alanine (D-Ala) component in bacterial peptidoglycan, chemotherapeutic D-Ala-OXA and photosensitizing D-Ala-PPa were firstly prepared and simultaneously labeled on MG1655, creating the multimodal platform (O/P@MG1655). When exposed to red light irradiation, O/P@MG1655 effectively eliminated tumor cells through chemo-photodynamic therapy and induced immunogenic cell death to trigger immunotherapy. Notably, significant inhibition of tumor growth and excellent biosafety were observed in a subcutaneous CT26 mouse tumor model. This dual metabolic modification strategy represents a remarkable advancement in the development of functionalized targeted bacteria for precise tumor treatment.
研究领域:
癌症治疗
·
细菌工程
·
光动力治疗
·
免疫疗法
·
肿瘤微环境
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）