BIOMACROMOLECULES
·
2024
·
IF 5.5
Yufei Cao,Moujiang Zheng,Jiahong Shi,Jiale Si,Guopu Huang,Yuanyuan Ji,Yuzhu Hou,Zhishen Ge
X-ray-induced photodynamic therapy (XPDT) can penetrate deeply into the tumor tissues to overcome the disadvantage of conventional PDT. However, the therapeutic efficacy of XPDT in cancer therapy is still restricted due to the insufficient reactive oxygen species (ROS) generation at a relatively low irradiation dosage. Herein, we present the tumor pH and ROS-responsive polyprodrug micelles to load the X-ray photosensitizer verteporfin (VP) as an ROS production enhancer. The block copolymer polyprodrug consisting of hydrophilic poly(ethylene glycol) (PEG) as well as the segments of thioketal-linked camptothecin (CPT) methacrylate (CPTKMA) and 2-(pentamethyleneimino)ethyl methacrylate (PEMA) (PEG-b-P(CPTKMA-co-PEMA)) can self-assemble into micelles in aqueous solution and encapsulate VP with a high loading efficiency of 67%. Inside tumor tissues, the zeta potential of the micelles can transform from neutral to positive for promoted cellular internalization under tumor acidity. Followed by X-ray irradiation at the dose of 4 Gy, efficient ROS generation in the presence of VP triggers CPT release. The VP-loaded polyprodrug micelles can finally ablate tumors efficiently via synergistic radiochemotherapy due to deep penetration of X-ray inside tumor tissues, ROS generation enhancement, and triggered CPT release. Consequently, this promising strategy represents a robust therapeutic modality for the enhanced radiochemotherapy of cancers.
研究领域:
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Zhongwen Yuan,Xinxin Liu,Jiabao Ling,Guanning Huang,Jiarun Huang,Xueqiong Zhu,Lizhen He,Tianfeng Chen
Disrupting redox homeostasis in the tumor microenvironment (TME), like excessive H 2 O 2 , glutathione (GSH) and weak acidity, has been proved as an effective tumor therapeutic strategy. Herein, we constructed a TME-responsive nanozyme , DOX@HMSN/Mn 3 O 4 (R), with reversible Mn 3+ /Mn 2+ transition in situ triggered by TME to perturb the intrinsic redox homeostasis and catalyze reactive oxygen species (ROS) overproduction. In addition, this nanozyme could react with excess GSH in TME to produce GSSG, resulting in the consumption of reducing agents to suppress ROS clearance. Density functional theory calculations further confirmed that the nanozyme mainly exhibited the oxidase-like activity to catalyze the formation of hydroxyl radicals from O 2 , thus strengthening the oxidation environment in the TME. Combined with radiotherapy , the high-energy X-ray could excite the outer-layer electrons in the nanozyme, forming photoelectrons that participate in the oxidase-like enzymatic reaction , thus intensifying ROS accumulation and amplifying the radio-/chemotherapeutic efficacy.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 15
·期 4
·4177-4184
·
IF 1.664
Zhengting Chen,Xinyi Cai,Li Chang,Yaoxiong Xia,Li Wang,Yu Hou,Lan Li,Dingguo Pan,Furong Li,Shan Liu,Wei Xiong,Wenhui Li
Concurrent radiotherapy and chemotherapy is a widely used, comprehensive treatment for rectal cancer. By studying the impact of concurrent chemoradiotherapy on the invasion and migration of colorectal cancer (CRC) cells and researching the associated molecular mechanisms, the present study aimed to provide a novel method to improve the therapeutic effect of this treatment against CRC. Human HCT116 and HT29 CRC cells were simultaneously treated with 4 Gy of 6 MV X‑rays and 10 µmol/l 5‑fluorouracil to establish a residual cell model. Transwell migration and invasion experiments were used to analyse the invasion and migration of the cells. The expression of long non‑coding (lnc)RNAs was detected using a gene chip, and reverse transcription‑quantitative polymerase chain reaction analysis was used to determine lncRNA expression levels. Specific small interfering RNAs were transfected into HCT116 residual cells to silence the expression of the identified key genes. The migration and invasion of residual CRC cells were demonstrated to be significantly increased compared with the original cells. Pvt1 oncogene, long‑chain non‑protein‑coding RNA 152 (LINC00152), and MIR22 host gene were selected as potential targets. However, the migration and invasion of residual HCT116 cancer cells were only significantly decreased following silencing of LINC00152 expression. LINC00152 may therefore be a potential biomarker involved in modulation of the biological characteristics of residual CRC cells following chemoradiotherapy.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2020
·
IF 14.588
Yiwei Kang,Xujiang Yu,Xinyang Fan,Aodenggerile,Shengzhe Zhao,Chunlai Tu,Zhiqiang Yan,Ruibin Wang,Wanwan Li,Huibin Qiu
The abundant species of functional nanomaterials have attracted tremendous interests as components to construct multifunctional composites for cancer theranostics. However, their distinct chemical properties substantially require a specific strategy to integrate them in harmony. Here, we report the preparation of a distinctive multifunctional composite by encapsulating small-sized semiconducting copper bismuth sulfide (CBS) nanoparticles and rare-earth down-conversion (DC) nanoparticles in larger-sized zeolitic imidazolate framework-8 (ZIF8) nanoparticles, followed by loading an anticancer drug, doxorubicin (DOX). Such composites can be used for tetramodal imaging, including traditional computed tomography and magnetic resonance imaging and, recently, for photoacoustic imaging and fluorescence imaging. With a pH-responsive release of the encapsulated components, synergistic radio-chemotherapy with a high (87.6%) tumor inhibition efficiency is achieved at moderate doses of the CBS&DC-ZIF8@DOX composite with X-ray irradiation. This promising strategy highlights the extending capacity of zeolitic imidazolate frameworks to encapsulate multiple distinct components for enhanced cancer imaging and therapy.
研究领域:
纳米医学
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肿瘤学
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生物材料学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Du Longhai,Zhu Guanghao,Xu Yanlong,Han Binxu,Wang Yu,Zhu Minhui,Meng Yingdi,Chen Huaiwen,Yu Zuochong
Introduction: The toxic side effects of systemic high-dose chemotherapy and poor sensitivity to radiotherapy hinder the survival rate of patients with osteosarcoma (OS). Nanotechnology offers new solutions for OS treatment; however, conventional nanocarriers suffer from inadequate targeting of tumors and short in vivo circulation time.Methods: Here, we designed a novel drug delivery system, [Dbait-ADM@ZIF-8]OPM, which uses OS-platelet hybrid membranes to encapsulate nanocarriers, to enhance the targeting and circulation time of nanocarriers, thereby enabling high enrichment of the nanocarriers in OS sites.Results: In the tumor microenvironment, the pH-sensitive nanocarrier, which is the metal-organic framework ZIF-8, dissociates to release radiosensitizer Dbait and the classical chemotherapeutic agent Adriamycin for the integrated treatment of OS via radiotherapy and chemotherapy. Benefiting from the excellent targeting ability of the hybrid membrane and the outstanding drug loading capacity of the nanocarrier, [Dbait-ADM@ZIF-8]OPM showed potent anti-tumor effects in tumor-bearing mice with almost no significant biotoxicity.Conclusion: Overall, this project is a successful exploration of the combination of radiotherapy and chemotherapy of OS treatment. Our findings solve the problems of the insensitivity of OS to radiotherapy and the toxic side effects of chemotherapy. Furthermore, this study is an expansion of the research of OS nanocarriers and provides new potential treatments for OS.
研究领域:
肿瘤学
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纳米技术
·
药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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