ACS Applied Polymer Materials
·
2023
·
IF 5
Jinjin Li,Ruyue Liu,Bingyan Zhang,Feifei Bai,Ling Zhao,Zhenhao Xi
In this work, a multimodal (chemotherapeutic/photodynamic/photothermal) theranostic nanodrug delivery platform was developed based on the synergetic action of self-framed polyphosphazene prodrug and heptamethine cyanine dye IR-780. First, an electronegative glutathione (GSH)-responsive polyphosphazene prodrug abbreviated as HGEH was prepared via multicomponent condensation reaction of genistein (GEN), bis-(4-hydroxyphenyl)-disulfide, and hexachlorocyclotriphosphazene. The particle size of drug (GEN)-containing HGEH nanoparticles is adjustable. Subsequently, cationic near-infrared photosensitizer IR-780 was adsorbed onto the electron-rich HGEH to obtain the multimodal theranostic nanodrug delivery platform HGEH-IR780. The platform was demonstrated to retain high stability in avoiding drug leakage and enable controlled drug release in response to the tumor microenvironment, in which a higher GSH concentration exists. The in vitro experiments show that HGEH-IR780 undergoes photothermal and photodynamic processes to concurrently generate heat and reactive oxygen species for efficiently killing mouse breast cancer cells (4T1) upon exposure to a single-bandwidth near-infrared laser (808 nm). Specifically, HGEH-IR780 inhibits 4T1 cells by up to 80% at a concentration of 100 μg/mL. The as-developed HGEH-IR780 exhibits promising results in GSH-responsive anticancer activity and photodynamic/photothermal therapy, which provides a reference for the construction of the polyphenol flavonoid multimodal therapeutic nanoplatform.
研究领域:
材料科学
·
药学
·
生物医学工程
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
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
·
纳米技术
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Taiyuan Liu,Xinghui Si,Liping Liu,Sheng Ma,Zichao Huang,Yu Zhang,Wantong Song,Yingchao Zhang,Xuesi Chen
Breast cancer is the most commonly diagnosed cancer, and surgical resection is the first choice for its treatment. With the development of operation techniques, surgical treatment for breast cancer is evolving toward minimally invasive and breast-conserving approaches. However, breast-conserving surgery is prone to an increased risk of cancer recurrence and is becoming a key challenge that needs to be solved. In this study, we introduce a one-shot injectable nano-in-gel vaccine (NIGel-Vax) for postoperative breast cancer therapy. The NIGel-Vax was constructed by mixing protein antigens with PEI-4BImi-Man adjuvant and then encapsulated in a hydrogel made with oxidized dextran (ODEX) and 4-arm PEG-ONH2. Using 4T1 tumor-extracted proteins as antigen, the NIGel-Vax achieved a 92% tumor suppression rate and a 33% cure rate as a postoperative therapy in the 4T1 tumor model. Using the tumor-associated antigen trophoblast cell-surface antigen 2 (TROP2) protein as the antigen, NIGel-Vax achieved a 96% tumor suppression rate and a 50% cure rate in triple-negative breast cancer (TNBC) models. This design provides an encouraging approach for breast cancer postoperative management.
研究领域:
肿瘤学
·
药理学
·
生物医学工程
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBON
·
2021
·
IF 9.594
Daochang Li,Yucai Zhang,Jing Xu,Fumi Yoshino,Huazhen Xu,Xiao Chen,Li Zhao
Multifunctional nanodevices have shown great promise as robust tools in cancer theranostics. Carbon nanohorns (CNHs) of large specific surface area, low toxicity and unique physicochemical properties are among one of ideal platforms to fabricate the nanodevices. Herein, we develop a water-dispersible carbon nanohorn−polyglycerol−gold (CNH-PG-Au) nanohybrid through surface engineering of CNHs, which is further loaded with chemotherapeutic drug doxorubicin (DOX) to afford [email protected] nanodevice. Benefiting from the excellent hydrophilicity of PG, as-prepared multifunctional [email protected] possesses good aqueous dispersibility and colloidal stability enabling biomedical applications. [email protected] nanoparticles are taken up by 4T1 mouse breast cancer cells and mainly disperse in the lysosomes, where the mild acidic condition promotes the release of DOX. [email protected] induces more cell apoptosis under X-ray irradiation than [email protected] of the same DOX concentrations, which is attributed to increased DNA damage by synergistic effect of DNA intercalation of DOX and radiosensitization of Au nanoparticles. Upon intravenous administration, [email protected] nanoparticles steadily accumulate in 4T1 tumor through enhanced permeability and retention (EPR) effect, and the tumor can be clearly observed by photoacoustic imaging. In vivo tumor treatment using [email protected] together with X-ray irradiation effectively inhibits tumor growth through radiochemotherapy. Our work demonstrates the great potential of [email protected] nanodevice in cancer theranostics.
研究领域:
纳米技术
·
癌症研究
·
生物医学工程
·
诊疗学
·
成像技术
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2020
·
IF 7.242
Zhaoming Guo,Ye Liu,Xiao Cheng,Dong Wang,Shubin Guo,Mingli Jia,Kun Ma,Changhao Cui,Li Wang,Hao Zhou
The heat shock response (HSR) induced by photothermal therapy (PTT), which can cause tumor cells to resist apoptosis, has increasingly attracted the attention of researchers. Synergistic treatment of tumors using multiple means to improve therapeutic efficiency would be a promising strategy for effective cancer treatment. In this study, a cancer cell membrane-camouflaged nanocarrier was developed and loaded with tellurium (Te) and cantharidin (CTD) for efficient combinatorial therapy. The designed nanoparticles ( [email protected] ) used a 4T1 cell membrane coating as the shell with homologous targeting capability, CTD as an the HSR inhibitor and antitumor drug, and Te as a PTT and photodynamic therapy (PDT) photosensitizer . An in vivo study indicated that the tumor inhibition rate of this combinatorial therapy could reach approximately 82.3% in 4T1 mammary tumor models. This study suggested that [email protected] , as a versatile biomimetic nanoplatform, provides a new alternative for more precise and effective tumor treatment. Statement of significance In this work, we constructed cell membrane-coated biomimetic nanoparticles ( [email protected] ) to suppress cancer effectively through synergistic treatment. The developed [email protected] nanoparticles presented strong homologous targeting capabilities. The encapsulated Te triggered PDT and PPT under the near-infrared laser irradiation. Subsequently, the PTT triggered the release of CTD, which could suppress the HSR of tumor and achieve chemotherapy. In addition, due to the presence of outer cell membrane coating, these [email protected] nanoparticles showed good biocompatibility to healthy cells.
研究领域:
纳米技术
·
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
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
·
2022
·
IF 15.304
Shuting Lu,Wei Feng,Xijuan Yao,Xinran Song,Jinhe Guo,Yu Chen,Zhongqian Hu
Nanodynamic therapy (NDT) based on reactive oxygen species (ROS) generation has been envisioned as a distinct modality for efficient cancer treatment. However, insufficient ROS generation and partial ROS consumption frequently limit the theraputic effect and outcome of NDT owing to the low oxygen (O 2 ) tension and high glutathione (GSH) level in tumor microenvironment (TME). To circumvent these critical issues, we herein proposed and engineered the biodegradable GSH-depletion Mn(III)-riched manganese oxide nanospikes (MnO x NSs) with the photosynthetic bacterial cyanobacteria (Cyan) as a high-efficient and synergistic platform to reshape TME by simultaneously increasing oxygen content and decreasing GSH level. Specifically, under the trigger of acidity, MnO x NSs reacted with photosynthetic oxygen can generate toxic singlet oxygen ( 1 O 2 ). Moreover, MnO x NSs significantly reduced intracellular GSH, resulting in decreased GPX4 activity, which induced tumor cell non-apoptotic ferroptosis . Consequently, this combined strategy based on coadministration with Cyan and MnO x NSs demonstrated the superior antitumor efficacy via amplification of oxidative stress in 4T1 tumor-bearing mice for the synergetic oxygen-augmented nanodynamic/ferroptosis therapy. This work highlights a facile synergistic micro-/nano-system with the specific capability of reshaping TME to augment the sensitivity and therapeutic efficacy of NDT in solid hypoxic tumor therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2023
·
IF 10.9
Yike Hou,Zhe Tang,Jabeen Farheen,Madiha Saeed,Lijia Luo,Wenzi Ren,Dandan Luo,Asim Mushtaq,Ruibo Zhao,Jian Ge,Zhangsen Yu,Yao Li,M. Zubair Iqbal,Xiangdong Kong
Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics. Although the efficiencies of vaccines are limited, they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells (DCs) for initiating high T cell immunity. Herein, antigen-loaded manganese oxide (Mn 3 O 4 ) triangular-shaped ultrasmall nanoparticles were prepared to stimulate DC-based immunotherapy under the guidance of T 1 magnetic resonance imaging. The FDA-approved triblock copolymer Pluronic® F-68 was used not only to transfer the phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles. Ovalbumin (OVA), a model antigen, was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn 3 O 4 @PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity. The Mn 3 O 4 @PF68-OVA nanovaccine (NV) induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells (BMDCs) by conventional methods supports the proliferation of intestine organoids, which are an innovative three-dimensional cytotoxicity evaluation system, thereby indicating their potential safety for in vivo cancer therapies. The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs. In addition, Mn 3 O 4 @PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages, which suggests improved immunity. Excitingly, vaccination with Mn 3 O 4 @PF68-OVA offer complete protection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor. In addition, the designed nanovaccine demonstrated high T 1 -MR imaging in the tumor, further justifying enhanced tumor accumulation and capability to real-time monitor the treatment procedure. This study presents a promising nanosystem to design an effective nanovaccine for T 1 -MR imaging-guided tumor immunotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
免疫学
·
磁共振成像
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INVESTIGATIONAL NEW DRUGS
·
2023
·Vol. 41
·期 5
·664-676
·
IF 3.4
Pan Mingzhu,Liu Yali,Sang Tian,Xie Jiajun,Lin Huishu,Wei Jianpeng,Shao Shuai,Zheng Yanying,Zhang Juan
Liposomal doxorubicin exhibits stronger drug accumulation at the tumor site due to the Enhanced Permeability and Retention (EPR) effect. However, the prognosis for the patient is poor due to this drug’s lack of targeting and tumor metastasis during treatment. Vascular epidermal growth factor receptor (VEGFR2) plays an important role in angiogenesis and cancer metastasis. To enhance antitumor efficacy of PEGylated liposomal doxorubicin, we constructed a VEGFR2-targeted and doxorubicin-loaded immunoliposome (Lipo-DOX-C00) by conjugating a VEGFR2-specific, single chain antibody fragment to DSPE-PEG2000-MAL, and then we inserted the antibody-conjugated polymer into liposomal doxorubicin (Lipo-DOX). The immunoliposome was formed uniformly with high affinity for VEGFR2. In vitro, Lipo-DOX-C00 enhanced doxorubicin internalization into LLC and 4T1 cells compared with non-conjugated, liposomal doxorubicin. In vivo, Lipo-DOX-C00 delivered DOX to tumor tissues effectively, which exhibited an improved antitumor and anti-metastasis efficacy in both LLC subcutaneous tumor models and 4T1 tumor models. In addition, the combined therapy of a VEGFR2–MICA bispecific antibody (JZC01) and Lipo-DOX-C00 achieved enhanced inhibition of cancer growth and metastasis due to activation of the immune system. Our study provides a promising approach to clinical application of liposomal doxorubicin.
研究领域:
肿瘤学
·
药学
·
免疫疗法
·
药物递送系统
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 38
·26630-26639
·
IF 3.9
Jian Liu,Changchun Wen,Miaomiao Hu,Juan Long,Jing Zhang,Minzhe Li,Xiang-Cheng Lin
Chemodynamic therapy (CDT) has received more and more attention as an emerging therapeutic strategy, especially transition metals with Fenton or Fenton-like activity have good effects in CDT research, manganese dioxide nanosheets (MnO2 NSs) and their complexes have become one of the most favored nanomaterials in CDT of tumors. CDT is mainly based on the role of reactive oxygen species (ROS) in tumor treatment, which have clear chemical properties and produce clear chemical reactions. However, their mechanism of interaction with cells has not been fully elucidated. Here, we performed CDT on mouse breast cancer cells (4T1) based on MnO2 NSs, extracted the metabolites from the 4T1 cells during the treatment, and analyzed the differences in metabolites by using high-resolution liquid chromatography-mass spectrometry (LC-MS). Untargeted metabolomics studies were conducted using the relevant data. This study mainly explored the changes in MnO2 NSs on the metabolite profile of 4T1 cells and their potential impact on tumor therapy, in order to determine the mechanism of action of MnO2 NSs in the treatment of breast cancer. The results of the study showed the presence of 11 different metabolites in MnO2 NSs CDT for 4T1 tumor cells, including phosphoserine, sphingine, phosphocholine, and stearoylcarnitine. These findings provide a deeper understanding of breast cancer treatment, and are beneficial for the further research and clinical application of CDT.
研究领域:
癌症研究
·
纳米技术
·
药理学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jianlin Lv,Yajun Xu,Ya Liu,Kazuo Sakurai,Haiyang Yu,Zhaohui Tang
ABSTRACT It is imperative to optimize chemotherapy for heightened anti-tumor therapeutic efficacy. Unrestrained tumor cell proliferation and sustained angiogenesis are pivotal for cancer progression. Plinabulin, a vascular disrupting agent, selectively destroys tumor blood vessels. Tirapazamine (TPZ), a hypoxia-activated prodrug, intensifies cytotoxicity in diminishing oxygen levels within tumor cells. Despite completing Phase III clinical trials, both agents exhibited modest treatment efficiency due to dose-limiting toxicity. In this study, we employed methoxy poly(ethylene glycol)- b -poly( D,L -lactide) (mPEG- b -PDLLA) to co-deliver Plinabulin and TPZ to the tumor site, concurrently disrupting blood vessels and eliminating tumor cells, addressing both symptoms and the root cause of tumor progression. Plinabulin was converted into a prodrug with esterase response (PSM), and TPZ was synthesized into a hexyl chain-containing derivative (TPZHex) for effective co-delivery. PSM and TPZHex were co-encapsulated with mPEG- b -PDLLA, forming nanodrugs (PT-NPs). At the tumor site, PT-NPs responded to esterase overexpression, releasing Plinabulin, disrupting blood vessels, and causing nutritional and oxygen deficiency. TPZHex was activated in response to increased hypoxia, killing tumor cells. In treating 4T1 tumors, PT-NPs demonstrated enhanced therapeutic efficacy, achieving a 92.9% tumor suppression rate and a 20% cure rate. This research presented an innovative strategy to enhance synergistic efficacy and reduce toxicity in combination chemotherapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xingyu Luo,Xiaolu Chen,Rongying Ma,Zhaoming Fu,Zuwei Liu,Qianhong Su,Huiling Fu,Yong Yang,Wei Xue
Cancer nanovaccines offer a promising strategy for fighting against tumors, however, the engineering of cancer nanovaccines that can be easily fabricated with tanglesome cancer cell-derived antigens and elicit an adequately strong tumor-specific cellular immunity remains challenging. Herein, metal-phenolic networks (MPNs) are used as an antigen delivery platform to prepare the mannose-modified MPNs nanovaccine loaded with ovalbumin (OVA) and the immunoadjuvant CpG oligodeoxynucleotide (MMOC) through the facile self-assembly. When the model antigen OVA is substituted with cancer cell membrane proteins (CCMPs), the nanovaccine is called MMCC. MMOC markedly activates dendritic cells (DCs) via the mannose-mediated endocytosis and efficiently promotes the antigen cross-presentation, thus inspiring a robust antigen-specific CD8 + T cell response as well as immune memory effect in vivo . Consequently, MMOC exhibits admirable therapeutic and preventive results on E.G7-OVA tumors. Moreover, the combination use of MMCC with anti-PD1 significantly inhibits the growth of 4T1 tumors by strengthening the cellular immunity and decreasing the proportion of regulatory T cells (Tregs). The survival rate of 4T1 tumor-bearing mice in the prophylaxis assay is maintained at 100 % by MMCC over 42 days. Altogether, this study affords a universal and effective nanovaccine preparation strategy for cancer immunotherapy and prevention.
研究领域:
癌症免疫学
·
纳米技术
·
生物医学工程
·
免疫治疗
✓ 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）