JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Weiran Cao,Xue Zhang,Rui Li,Zijie Li,An Lu,Fei Yu,Lu Sun,Jiancheng Wang,Zhiyu Wang,Huining He
FOLFOX regimen, composed of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (OXP), has been used as clinical standard therapeutic regimen in treatments of colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC). To further improve its therapeutic outcomes, FOLFOX was combined with anti-PD-1 antibody to form an advanced chemo-immune combination strategy, which has been proven more efficient in controlling cancer progression and prolonging patients' survival in various clinical trials. However, bad tumor accumulation, relative high toxicity, numerous treatment cycles with high fees and low compliance as well as drug resistance seriously limit the prognosis of FOLFOX regimen. The “all-in-one” formulations, which could precisely delivery multidrug regimen into tumor sites and cells, showed a promising application prospect for targeted drug delivery as well as reducing side effects. However, the design and preparation of the “all-in-one” formulation with high drug encapsulation efficiencies for all drugs was still challenging. Herein, a lipid core-shell nanoparticle codelivery platform was designed for simultaneous encapsulation of variant FOLFOX composed of miriplatin (MiPt), 5-Fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP), calcium folinate ( CF ) and PD-L1 siRNA (siPD-L1) with high efficiencies, and their synergistic anti-tumor mechanisms were studied, respectively. MiPt, a precursor of OXP, was validated capable of inducing efficient immunogenic cell death (ICD) in this work. Additionally, ICD-mediated release of damage associated molecular patterns functionalized synergistically with PD-L1 silence by siPD-L1 to overcome chemoresistance, reverse suppressive tumor microenvironment and recruit more CD8 + T cells. FdUMP, as the intracellular active form of 5-FU, could induce large amounts of reactive oxygen species to enhance the ICD. CF worked as the sensitizer of FdUMP. The enhanced long-term anti-tumor effect of the prepared “all-in-one” formulation compared to free drug regimen and other controls, was verified in heterotopic CRC mice models and ESCC mice models, providing new thoughts for researchers and showing a promising prospect of translation into clinical applications.
研究领域:
纳米技术
·
癌症研究
·
药学
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Xianglong Yu,Ning Han,Ziyi Dong,Yunni Dang,Qing Zhang,Wenjun Hu,Changhai Wang,Shouying Du,Yang Lu
Tumor metastasis and recurrence are recognized to be the main causes of failure in cancer treatment. To address these issues, an “all in one” and “one for all” nanoplatform was established for combined “chemo–immuno–photothermal” therapy with the expectation to improve the antitumor efficacy. Herein, Docetaxel (DTX, a chemo-agent) and cynomorium songaricum polysaccharide (CSP, an immunomodulator) were loaded into zein nanoparticles coated by a green tea polyphenols/iron coordination complex (GTP/FeIII, a photothermal agent). From the result, the obtained nanoplatform denoted as DTX-loaded Zein/CSP-GTP/FeIII NPs was spherical in morphology with an average particle size of 274 nm, and achieved pH-responsive drug release. Moreover, the nanoplatform exhibited excellent photothermal effect both in vitro and in vivo. It was also observed that the nanoparticles could be effectively up take by tumor cells and inhibited their migration. From the results of the in vivo experiment, this nanoplatform could completely eliminate the primary tumors, prevent tumor relapses on LLC (Lewis lung cancer) tumor models, and significantly inhibit metastasis on 4T1 (murine breast cancer) tumor models. The underlying mechanism was also explored. It was discovered that this nanoplatform could induce a strong ICD effect and promote the release of damage-associated molecular patterns (DAMPs) including CRT, ATP, and HMGB1 by the dying tumor cells. And the CSP could assist the DAMPs in inducing the maturation of dendritic cells (DCs) and facilitate the intratumoral infiltration of T lymphocytes to clear up the residual or disseminated tumor cells. In summary, this study demonstrated that the DTX-loaded Zein/CSP-GTP/FeIII is a promising nanoplatform to completely inhibit tumor metastasis and recurrence.
研究领域:
纳米技术
·
癌症研究
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-15
·
IF 10.2
Tan Xi,Wang Chenhui,Zhou Hong,Zhang Shuting,Liu Xuhan,Yang Xiangliang,Liu Wei
Typical chemo-immunotherapy against malignant carcinoma, is characterized by the combined application of chemotherapeutic agents and monoclonal antibodies for immune checkpoint blockade (ICB). Temporary ICB with antibodies would not depress tumor intrinsic PD-L1 expression and potential PD-L1 adaptive upregulation during chemotherapy, thus exerting limited immunotherapy efficacy. Herein, we developed novel polymer-lipid hybrid nanoparticles (2-BP/CPT-PLNs) for inducing PD-L1 degradation by inhibiting palmitoylation with bioactive palmitic acid analog 2-bromopalmitate (2-BP) to replace PD-L1 antibody (αPD-L1) for ICB therapy, thus achieving highly efficient antitumor immune via immunogenic cell death (ICD) induced by potentiated chemotherapy. GSH-responsive and biodegradable polymer-prodrug CPT-ss-PAEEP10 assisted as a cationic helper polymer could help to stabilize 2-BP/CPT-PLNs co-assembled with 2-BP, and facilitate the tumor site-specific delivery and intracellular release of water-insoluble camptothecin (CPT) in vivo. 2-BP/CPT-PLNs would reinforce cytotoxic CD8+ T cell-mediated antitumor immune response via promoting intratumoral lymphocytes cells infiltration and activation. 2-BP/CPT-PLNs significantly prevented melanoma progression and prolonged life survival of mice beyond the conventional combination of irinotecan hydrochloride (CPT-11) and αPD-L1. Our work first provided valuable instructions for developing bioactive lipid analogs-derived nanoparticles via lipid metabolism intervention for oncotherapy.Graphical Abstract
研究领域:
纳米技术
·
癌症治疗
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免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Shiji Fang,Liyun Zheng,Gao-Feng Shu,Chen Xiaoxiao,Xiaoju Guo,Yiming Ding,Wenjing Yang,Jiale Chen,Zhongwei Zhao,Jianfei Tu,Minjiang Chen,Jian-Song Ji
Immunotherapy is the most promising systemic therapy for hepatocellular carcinoma. However, the outcome remains poor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in altering cell-surface protein levels, potentially undermining the efficacy of immunotherapy against tumors. This highlights its potential as a target for antitumor therapy. Herein, CaCO3-based nanoparticles coencapsulated with DOX, an immunogenic cell death (ICD) inducer, and evolocumab was developed to enhanced the efficacy of immunotherapy. The obtained DOX/evolocumab-loaded CaCO3 nanoparticle (named DECP) exhibits a good capacity of acid neutralization and causes ICD of cancer cells. In addition, DECP is able to evaluate the cell-surface level of MHC-I, a biomarker that correlates positively with patients’ overall survival. Upon intravenous injection, DECP accumulates within the tumor site, leading to growth inhibition of hepa1-6 bearing subcutaneous tumors. Specifically, DECP treatment causes augmented ratios of matured dendritic cells, tumor-infiltrating CD8+ T cells and natural killing cells, while concurrently depleting Foxp3+ regulatory T cells. Peritumoral delivery of DECP enhances the immune response of distant tumors and exhibits antitumor effects when combined with intravenous αPD-L1 therapy in a bilateral tumor model. This study presents CaCO3-based nanoparticles with multiple immunomodulatory strategies against hepatocellular carcinoma by targeting PCSK9 inhibition and modulating immune homeostasis in the unfavorable TME.
研究领域:
肿瘤学
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免疫学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Jie Yang,Siyu Ma,Rui Xu,Yawen Wei,Jun Zhang,Tiantian Zuo,Zhihua Wang,Huizi Deng,Ning Yang,Qi Shen
Antitumor immunotherapy is limited by low tumor immunogenicity and immunosuppressive microenvironment (TIME), which could be improved by “ROS-ferroptosis-glycolysis regulation” strategy. Herein, a cancer cell membrane coated metal organic framework (MOF) loading with glucose oxidase (GOx) and doxorubicin (DOX) was constructed (denoted as mFe(SS)/DG). Benefiting from the homotypic targeting of cancer cell membrane, the nanoplatform effectively accumulated in tumors. mFe(SS)/DG based on coordination between Fe 3+ and disulfide-bearing ligand scavenged GSH and downregulated glutathione peroxide 4 (GPX4) to trigger ferroptosis. GOx catalyzed glucose to generate abundant H 2 O 2 for enhancing Fenton reaction, resulting in excessive ROS in tumors. The ROS burst simultaneously promoted ferroptosis and inhibited glycolysis. Ferroptosis combined with DOX induced immunogenic cell death (ICD) and released tumor antigens to initiate antitumor immunity. Glycolysis repression remodeled TIME by decreasing lactate to solidify and boost the antitumor immunity. The smart biomimetic nanoplatform integrates tumor metabolism and immunity based on ROS-ferroptosis-glycolysis regulation, providing a potential anti-tumor strategy.
研究领域:
癌症研究
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纳米技术
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免疫疗法
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生物化学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Minghao Sun,Weiwei Liu,Yuanyuan Ma,Pengfei Ni,Wenjing Yao,Yingjie Xu,Rui Bao,Jue Wang,Fei Xiong,Xihe Kuang,Teng Zhang,Xiaochen Zhang,Xikuang Yao,Shenghong Ju,Wenpei Fan
Chemodynamic therapy (CDT) efficacy in the tumor microenvironment (TME) remains compromised. Inspired by the potential of fever-like heat to activate a redox-favorable microenvironment, mild photothermal therapy (mPTT) is expected to sensitize tumors to CDT, turning “redox-cold” tumors into “redox-hot” ones. Herein, an injectable gel engine (LMFT@SG-R) is meticulously constructed based on the co-encapsulation of R848 and β-lapachone (LAP)-loaded metal–organic framework-199 (MOF-199) within a lipidic gel reservoir with the unique ability of thermally reversible sol–gel phase transformation. With mPTT reprogramming TME, the custom-designed LMFT@SG-R can realize systemic redox homeostasis remodeling through mPTT-activated chemodynamic immunotherapy (MPCIT). Once reaching the TME, LMFT@SG-R quickly hydrates into solid gel and subsequently undergoes gel-to-sol transformation under mild NIR laser irradiation, resulting in on-demand release of LMFT and R848 for controllable CDT and immunostimulation. LMFT undergoes stepwise degradation for sequential release of Fe 3+ , Cu 2+ and LAP, which can promote ROS cascade amplification owing to the upregulation of HSP70/NQO1 axis upon mild hyperthermia, resulting in robust ICD effects and T lymphocytes infiltrations together with R848. Notably, the controllable immunostimulation can facilitate robust abscopal effects and prominent suppression of distal tumors. The well-designed LMFT@SG-R may represent an updated CDT catalyst with the highly-integrated gel engine for chained-cooperative MPCIT.
研究领域:
癌症治疗
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生物医学工程
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免疫疗法
·
化学生物学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 27
·2201834
·
IF 17.521
Xiao Sang,Tong Gao,Xiaoqing Liu,Yelong Shen,Lili Chang,Shunli Fu,Han Yang,Huizhen Yang,Weiwei Mu,Shuang Liang,Zipeng Zhang,Na Zhang,Yongjun Liu
Photothermal therapy (PTT) is a promising strategy for cancer treatment, but its clinical application relies heavily on accurate tumor positioning and effective combination. Nanotheranostics has shown superior application in precise tumor positioning and treatment, bringing potential opportunities for developing novel PTT-based therapies. Here, a nanotheranostic agent is proposed to enhance magnetic resonance imaging (MRI)/ near-infrared fluorescence imaging (NIRFI) imaging-guided photo-induced triple-therapy for cancer. Thermosensitive liposomes co-loaded with SPIONs/IR780 and Abemaciclib (SIA-TSLs), peptide ACKFRGD, and click group 2-cyano-6-amino-benzothiazole (CABT) are co-modified on the surface of SIA-TSLs to form SIA- α TSLs. ACKFRGD can be hydrolyzed to expose the 1, 2-thiolamino groups in the presence of cathepsin B in tumors, which click cycloaddition with the cyano group on CABT, resulting in the formation of SIA- α TSLs aggregates. The aggregation of SIA- α TSLs in tumors enhances the MRI/NIRFI imaging capability and enables precise PTT. Photo-induced triple-therapy enhances precision cancer therapy. First, PTT ablates specific tumors and induces ICD via localized photothermal. Second, local tumor heating promotes the rupture of SIA- α TSLs, which release Abemaciclib to block the tumor cell cycle and inhibit Tregs proliferation. Third, injecting GM-CSF into tumor tissue leads to recruitment of dendritic cells and initiation of antitumor immunity. Collectively, these results present a promising nanotheranostic strategy for future cancer therapy.
研究领域:
生物医学工程
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癌症治疗
·
医学影像
·
纳米技术
·
药学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Zhilin Li,Hao Cai,Zhiqian Li,Long Ren,Xuelei Ma,Hongyan Zhu,Qiyong Gong,Hu Zhang,Zhongwei Gu,Kui Luo
To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as “eat me” signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
生物医学工程
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2024
·
IF 5.5
Junfeng Ding,Tianran Wang,Yan Rong,Chaoliang He,Xuesi Chen
Comprehensive Summary Due to the immunosuppressive tumor microenvironment (TME), T cells are usually inactivated and tend to differentiate into regulatory T cells (Tregs) in the tumor tissues, which seriously hinders the anti-tumor efficiency of immunotherapy. In this study, an immune-stimulating polypeptide hydrogel conjugated with an indoleamine-2,3-dioxygenase (IDO) inhibitor, 1-methyl- D -tryptophan (D1MT), through a glutathione (GSH)-responsive spacer was developed as an immunotherapy platform capable of regulating the TME. A combined immunotherapy system was further constructed through encapsulating doxorubicin (Dox) and immune checkpoint blocking antibody targeting programmed cell death protein 1 (aPD-1) in the hydrogel. Dox released from the hydrogel could cause the immunogenic cell death (ICD) of tumor cells and induce the maturation of antigen presenting cells (APCs). After intratumoral injection, the multiple agent-loaded hydrogel elicited effective anti-tumor immunity in mice bearing B16F10 melanoma. Moreover, compared with the control hydrogel without D1MT, the immune-stimulating hydrogel showed better efficiency in improving the immunosuppressive TME with increased number of activated T cells and reduced number of Tregs. Therefore, the immune-stimulating hydrogel has great potential as a stimuli-responsive platform for regulating suppressive TME and enhanced anti-tumor chemo-immunotherapy.
研究领域:
癌症免疫疗法
·
药学
·
生物医学工程
·
免疫学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2023
·
IF 17.4
Nan Wang,Pin Li,Jing Zhao,Yamin Liu,Xi Hu,Daishun Ling,Fangyuan Li
Photoimmunotherapy, which not only directly kills tumor cells but also elicits antitumor immune responses by inducing immunogenic cell death (ICD), has emerged as a promising approach for cancer treatment. However, the hypoxic immunosuppressive tumor microenvironment (TME) with limited immune response immensely compromises the therapeutic outcomes. Herein, an end-deposited plasmonic catalyst (GCNRs) is developed by selectively depositing semiconducting ceria nanosheets onto the two ends of gold nanorods for plasmonic catalysis-mediated TME modulation. Specially, an efficient low-power near-infrared-triggered electron-hole spatial separation along the longitudinal axis of GCNRs occurs due to the end-deposition morphology. The generated hot electrons and hot holes separately participate in the reactive oxygen species (ROS) generation and oxygen-evolution half-reaction, thereby modulating the immunosuppressive TME via concurrent ROS-mediated ICD-induction and H 2 O 2 -independent hypoxia relief. Unprecedentedly, mere injection of GCNRs can induce significant infiltration of cytotoxic T cells into tumor tissues, significantly inhibiting the growth and metastasis of tumors. Our study represents a promising plasmonic catalysis-mediated TME modulation strategy in phototherapy-based immuno-oncology.
研究领域:
癌症治疗
·
免疫学
·
纳米技术
·
光催化
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Xian Tang,Jingdong Rao,Sheng Yin,Jiaojie Wei,Chunyu Xia,Man Li,Ling Mei,Zhirong Zhang,Qin He
The Cancer-Immunity Cycle is a series of anticancer immune responses initiated and allowed to proceed and expand iteratively. Paclitaxel (PTX) is a classic chemotherapeutic agent, which could induce immunogenic cell death (ICD) to trigger the Cancer-Immunity Cycle. However, the Cycle is severely impaired by tumor cell immunosuppression of host T cell antitumor activity through the programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) (PD-1/PD-L1) immune checkpoint pathway. Here, we demonstrated that PTX mediated the Cancer-Immunity Cycle could be enhanced by PD-L1 knockdown (KD) and followed mTOR pathway inhibition in tumor cells. PD-L1 siRNA (siP) and the hydrophobic chemotherapy drug PTX were co-delivered with a rationally designed hybrid micelle (HM). We showed clear evidence that the HM-siP/PTX is capable of delivering siP and PTX simultaneously to the B16F10 cells both in vitro and in vivo . We demonstrated that HM-PTX/siP reduced the expression of PD-L1 and p-S6K (a marker of mTOR pathway activation) both in vitro and in melanoma-bearing mice and attenuated synergistically tumor growth by chemical toxicity , promoting cytotoxic T-cell immunity and suppressing the mTOR pathway.
研究领域:
肿瘤学
·
免疫治疗
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Methods
·
2023
·Vol. 7
·期 5
·2201327
·
IF 12.4
Xinyang Li,Yang Luo,Zhengjie Huang,Yi Wang,Jian Wu,Shaobing Zhou
In the treatment of solid tumors, the complex barriers composed of cancer-associated fibroblasts (CAFs) prevent drug delivery and T cells infiltration into tumor tissues. Although nanocarriers hold great prospects in drug delivery, fibrosis causes the biological barrier and immunosuppressive tumor microenvironment (ITM) that impairs the anti-tumor efficacy of nanocarriers. Here, a small dendritic macromolecule loaded with doxorubicin (PAMAM-ss-DOX) (DP) is synthesized and encapsulated into pH-responsive nanoliposome, together with adjuvant toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and losartan (LOS). The pH-responsive liposome facilitates the simultaneous and effective delivery of DP, R848, and LOS, which can decompose and release these drugs under the acidic tumor microenvironment. The small sized DP (≈25 nm) with the ability to penetrate into tumor tissue and immunogenic cell death (ICD) can reverse the ITM and elicit immune response, which is equivalent to the effect of an in situ vaccine. Moreover, LOS reduces the activity of CAFs effectively, which can contribute to the infiltration of T cells. Therefore, this nano-platform provides a new therapeutic strategy for enhanced chemo-immunotherapy.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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