BIOMATERIALS
·
2016
·
IF 8.387
Leyong Zeng,Yuanwei Pan,Ruifen Zou,Jinchao Zhang,Ying Tian,Zhaogang Teng,Shouju Wang,Wenzhi Ren,Xueshan Xiao,Jichao Zhang,Lili Zhang,Aiguo Li,Guangming Lu,Aiguo Wu
To avoid the overheating effect of excitation light and improve the efficacy of photodynamic therapy (PDT) of upconversion nanoplatform, a novel nanoprobe based on 808 nm-excited upconversion nanocomposites ( [email protected] @mSiO 2 ) with low heating effect and deep penetration has been successfully constructed for targeted upconversion luminescence , magnetic resonance imaging (MRI) and high-efficacy PDT in HER2-overexpressed breast cancer. In this nanocomposite, photosensitizers (Ce6) were covalently conjugated inside of mesoporous silica to enhance the PDT efficacy by shortening the distance of fluorescence resonance energy transfer and to decrease the cytotoxicity by preventing the undesired leakage of Ce6 . Compared with [email protected] 2 @Ce6, [email protected] @mSiO 2 greatly promoted the singlet oxygen generation and amplified the PDT efficacy under the excitation of 808 nm laser . Importantly, the designed nanoprobe can greatly improve the uptake of HER2-positive cells and tumors by modifying the site-specific peptide, and the in vivo experiments showed excellent MRI and PDT via intravenous injection by modeling MDA-MB-435 tumor-bearing nude mice . Our strategy may provide an effective solution for overcoming the heating effect and improving the PDT efficacy of upconversion nanoprobes, and has potential application in visualized theranostics of HER2-overexpressed breast cancer.
研究领域:
纳米技术
·
癌症研究
·
治疗诊断学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Yue Wu,Na Liu,Xiao-Xia Ren,Wen-Chao Zhang,Jing Qian
Combination therapy could significantly improve the therapeutic effect of tumors. However, due to the lack of reasonable integration of different treatment modes, it is difficult to maximize the effect of combination treatment. To solve this problem, by adjusting the dosage of NH4F/NaOH, we developed NaTmF4:0.5%Er3+@NaLuF4 upconversion nanoparticles with strong near-infrared luminescence. On this basis, nanocarriers (USFH-CI) encapsulated with high-loading (33.35%) Fe(acac)3, wrapped by human serum albumin, and grafted with cinnamic aldehyde (CA) and the IR780 photosensitizer were constructed. The dense extracellular matrix (ECM) in tumor tissues prevented the drug from diffusing into the tumors. Once USFH-CI nanocarriers were delivered to the tumor area, CA pH-responsively released H2O2, which promoted photothermal therapy (PTT) and photodynamic therapy (PDT) of IR780 driven by upconversion luminescence. A large number of reactive oxygen species (ROS) were generated, which led to the disintegration of the ECM and penetration into the tumors. Then, abundant Fe3+ consumed GSH to generate ample GSSG and Fe2+, which enhanced the sensitivity of tumor cells to oxidative stress, thus leading to the accumulation of lipid peroxide (LPO) and finally inducing ferroptosis. At the same time, substantial H2O2 and Fe2+ triggered off the Fenton-like reaction, releasing affluent free radicals. Beyond that, PTT of IR780 further promoted the Fenton-like reaction, and the generation of ROS was amplified. Free radicals generated in the process of ferroptosis destroyed heat shock protein produced by PTT, which solved the self-protection of cancer cells against heat. In situ ROS generation by the PTT/PDT of IR780 and the Fe2+ Fenton-like reaction further promoted the accumulation of LPO and ferroptosis as well as deep penetration, which maximized the effect of combination treatment and achieved a high tumor inhibition rate (84.71%). Also, there was negligible damage to normal tissues with good tumor targeting and digestive metabolism.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
·
光化学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Haoyu Chen,Xiaoying Kong,Jiahui Yan,Tianyi Wang,Yaqian Lv,Fenglang Zhang,Danping Liu,Yingshan Qu,Jun Fu,Wei Han,Jinsheng Shi
Combined dynamic tumor therapy of photodynamic therapy (PDT), sonodynamic therapy (SDT) and microwave dynamic therapy (MDT) can overcome the limitations of single reactive oxygen species (ROS)-based therapy (including limited tissue penetration depth and low ROS production). However, changes in the tumor microenvironment caused by ROS amplification and oxygen depletion induce severe immunosuppression at the tumor site, indicating effective immunosensitization of the tumors are urgently needed. Here, melanin-hematoporphyrin-chloroquine R837-hyaluronic acid (MHRH) nanoplatform that can simultaneously respond to 980 nm laser /1064 nm laser/ultrasonic/microwave was prepared for PDT/SDT/MDT, achieving outbreak of ROS in deep tumor. More importantly, the photothermal ablation and the participation of chloroquine R837 of MHRH NPs reversed the immunosuppression caused by oxygen depletion after ROS outbreak by promoting DCs maturation and secretion of macrophage exosomes. In summary, the natural MHRH nano-platform supplies an obvious anti-tumor “butterfly effect” through ROS outbreak, thermal ablation and significant immunosuppressive reversal, which provides a new and promising combined strategy of ROS-dynamic therapy and immune agonists in deep tumor tissues.
研究领域:
癌症治疗
·
纳米技术
·
免疫治疗
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Feiyang Jin,Jing Qi,Minxia Zhu,Di Liu,Yuchan You,Gaofeng Shu,Yan Du,Jun Wang,Hui Yu,Mingchen Sun,Xiaoling Xu,Qiying Shen,Xiaoying Ying,Jiansong Ji,Yongzhong Du
A desirable cancer therapeutic strategy is supposed to have effective ability to not only exert maximum anticancer ability but also inspire antitumor immunity for preventing tumor relapse and metastasis. During this research, multifunctional upconversion nanoparticles (UCNPs) coated by ROS-responsive micelles are prepared for tumor targeting and near-infrared (NIR)-triggered photodynamic therapy (PDT)-combined synergistic effect of chemotherapy. Moreover, both PDT and chemotherapy agents could activate antitumor immunity via inducing immunogenic cell death with CD8+ and CD4+ T cells infiltrating in tumors. Through the experiments, intravenous administration of multifunctional nanocarriers with noninvasive NIR irradiation destroys the orthotopic tumors and efficiently suppresses lung metastasis in a metastatic triple-negative breast cancer model by cascade-amplifying chemo-PDT and systemic antitumor immunity. In conclusion, this study provides prospective chemo-PDT with inspired antitumor immunity for metastatic cancer treatment.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Zhongxi Xie,Shuang Liang,Xuechao Cai,Binbin Ding,Shanshan Huang,Zhiyao Hou,Ping’an Ma,Ziyong Cheng,Jun Lin
Hypoxia and overexpression of glutathione (GSH) are typical characteristics of the tumor microenvironment, which severely hinders cancer treatments. Here, we design a novel biodegradable therapeutic system, O2–Cu/ZIF-8@Ce6/ZIF-8@F127 (OCZCF), to simultaneously achieve GSH depletion and O2-enhanced combination therapy. Notably, the doped Cu2+ doubles the O2 storage capacity of the ZIF-8 matrix, which makes OCZCF an excellent pH-sensitive O2 reservoir for conquering tumor hypoxia, enhancing the photodynamic therapy (PDT) efficiency of chlorin e6 (Ce6) under 650 nm laser irradiation. Moreover, the released Cu2+ can act as a smart reactive oxygen species protector by consuming intracellular GSH. The byproduct Cu+ will undergo highly efficient Fenton-like reaction to achieve chemodynamic therapy (CDT) in the presence of abundant H2O2. The accompanying O2 will further alleviate hypoxia. The in vitro and in vivo experimental data indicate that OCZCF could cause remarkable tumor inhibition through enhanced synergetic PDT and CDT, which may open up a new path for cancer therapy.
研究领域:
癌症研究
·
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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Xiao Liu,Yuan Zhang,Peng Zhang,Kang Ge,Ruzhi Zhang,Yixin Sun,Yang Sheng,Mark Bradley,Rong Zhang
Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an important approach for the treatment of some skin diseases and cancers. A major defect of this approach is that it is difficult for 5-ALA to accumulate around lesions in deeper regions of tissue, resulting in poor conversion to the active fluorophore and photodynamic efficiencies. Because of their targeting and controlled release abilities, nanogel carriers could solve this problem. In this paper, nanogels were prepared by using micro-emulsion polymerization with various biodegradable polyester crosslinkers ( L -lactide and ε-caprolactone). The swelling and degradation properties and entrapment efficiency, drug loading and drug release ability of the nanogels were investigated. Nanogels co-cultured with skin cancer cells (A2058) allowed the efficiency of the PDT in vitro to be demonstrated. The results showed that the swelling rate of hydrogels reduced with increasing crosslinker levels, which caused a slow-down in the release of 5-ALA, but lipase accelerated degradation of nanogels increased 5-ALA concentrations in tumor cells and leading to higher PDT efficiency. It was proved by in vivo experiment indicating that the development of skin cancer tissues were efficiently inhibited by the 5-ALA loaded nanogels.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2022
·Vol. 14
·期 23
·8441-8453
·
IF 8.307
Dongsheng Zhang,Yanfei Meng,Yingzi Song,Ping Cui,Zunfu Hu,Xiuwen Zheng
With the advancement and development of nanomedicine, tumor precision therapy provides technical support for effective accumulation and targeted drug delivery, and reduces toxic side effects. In cancer cells, breaking the redox balance could induce cancer cell death. Herein, a novel iron-containing intelligent hydrogel nanobot (FeSe2–Ce6/MOF@HA/PEI/CpG@HHPA NPs, abbreviated as FSMH) is proposed to break the intracellular redox balance and trigger the immune response. The as-fabricated multifunctional FSMH could not only exert Fenton reactions in the acidic tumor microenvironment, converting hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (˙OH), but also effectively consume GSH to attenuate the intracellular oxidative stress. The negative charge of the FSMH nanohydrogel system guarantees its superexcellent stabilization in blood circulation and optimal tumor collection. Subsequently, the surface charge of the endocytosed FSMH was transformed to a positive charge after exposure to the acidic tumor environment, further improving its tumor collection and locally releasing Fe ions and immune adjuvants. Furthermore, Ce6 was released in a pH-responsive manner in the acidic microenvironment. In the presence of near-infrared light, singlet oxygen was produced by the FSMH nanohydrogel system, to ablate tumors and promote the maturation of dendritic cells, achieving the precision-combined strategies effect of CDT, PDT, and immunotherapy.
研究领域:
纳米医学
·
癌症治疗
·
生物医学工程
·
材料科学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Weicai Wang,Yuanyuan Wang,Minghui Ma,Hyung Jong Jin,Xuemei Li
The construction of completely biocompatible and biodegradable tumor suppressors by a simple and reliable method is essential for the clinical application of cancer-targeted drugs. Herein, by inserting glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) into human serum albumin (HSA) assembly molecules, we constructed a cancer-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT). The modification of HSA could block the GOx activity and reduce the cytotoxicity of normal cells and organs. Through active targeting and passive enhanced permeability and retention effect, the loading of AS1411 could promote the cascade bioreactors to effectively target nucleolin-overexpressed tumors. Once internalized by cancer cells, as a result of catalyzing hydrogen peroxide (H2O2) to produce oxygen (O2), the protein nano-cascade reactor promoted microenvironmental oxygenation, which would subsequently lead to an increase in cytotoxic singlet oxygen (1O2) production under light irradiation as well as the decomposition of intracellular glucose. In vitro and in vivo studies showed that the cascaded nanoreactors could significantly enhance therapeutic efficacy through synergistic starvation therapy and enhanced PDT as well as chemotherapy. This cascade strategy will be demonstrated in clinical applications with huge potential.
研究领域:
癌症研究
·
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
INORGANIC CHEMISTRY COMMUNICATIONS
·
2023
·
IF 3.8
Feng Ouyang,Li Zhao,Qi Shuai
Viscous tumour tissue seriously affects the effective delivery of nanodrugs and reduces their anti-tumour effect. In order to solve this problem, a nanomotor (Cy7@ZIF-8@TPZ) for penetrating tumour tissue was synthesized. A new amphiphilic molecule Cy7 was designed and synthesized to wrap ZIF-8 loaded with TPZ to obtain the final nanomotor. The synthesized Cy7 can not only realize photodynamic therapy (PDT) and photothermal therapy (PTT) simultaneously under single-wavelength illumination, but also promote the movement of nanoparticles through thermal drive. Through the targeting ability of Cy7 and the enhanced permeability and retention (EPR) effect, the nanomotor can conduct directional deep puncture under illumination. The oxygen continuously consumed by PDT further activates hypoxia-activated chemotherapy, and the combined PTT/PDT/hypoxia-activated CT therapy greatly enhances the anti-tumour efficacy of Cy7@ZIF-8@TPZ. In addition, light-degradable Cy7, acid-degraded ZIF-8 and hypoxia-activated TPZ greatly reduce the side effects of nanomotors.
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
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Ziyuan Huang,Yuying Chen,Jiulong Zhang,Wenpan Li,Menghao Shi,Mingxi Qiao,Xiuli Zhao,Haiyang Hu,Dawei Chen
There are two severe obstacles in cancer immunotherapy. The first is that the low response rate challenges the immune response owing to the immunosuppressive tumor microenvironment (ITM) and poor immunogenicity of the tumor. The second obstacle is that the dense and intricate pathophysiology barrier seriously restricts deep drug delivery in solid tumors. A laser/glutathione (GSH)-activatable nanosystem with tumor penetration for achieving highly efficient immunotherapy is reported. The core of the nanosystem was synthesized by coordinating zinc ions with GSH-activatable oxaliplatin (OXA) prodrugs and carboxylated phthalocyanine. Such an OXA/phthalocyanine-based coordination polymer nanoparticle (OPCPN) was wrapped by a phospholipid bilayer and NTKPEG. NTKPEG is a PEGylated indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor prodrug containing a thioketal (TK) linker, which was modified on the OPCPN (OPCPN@NTKPEG). Upon the laser irradiation tumor site, ROS production of the OPCPN@NTKPEG triggers cleavage of NTKPEG by degradation of TK for promoted tumor penetration and uptake. OXA, phthalocyanine, and IDO1 inhibitor were released by the intracellular high-level GSH. OXA inhibits cell growth and is combined with photodynamic therapy (PDT) to induce immunogenic cell death (ICD). The IDO1 inhibitor reversed the ITM by suppressing IDO1-mediated Trp degradation and exhaustion of cytotoxic T cells. Laser/GSH-activatable drug delivery was more conducive to enhancing ICD and reversing ITM in deep tumors. Chemo-PDT with OPCPN@NTKPEG significantly regressed tumor growth and reduced metastasis by improved cancer immunotherapy.
研究领域:
癌症研究
·
纳米技术
·
免疫治疗
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Yanling Xiao,Yuying Yuan,Manshan Liang,Jiahao Ni,Lichao Yu,Zu-Sheng Huang,Bing Du,Yun-Yun Quan
Fluorescence imaging-guided photodynamic therapy (PDT) is considered as an ideal alternative strategy to treat tumors. However, insufficient supply of oxygen in solid tumor tissue, aggregation-caused quenching (ACQ) of photosensitizers (PSs), poor targeting-specificity of cancer cells and short wavelengths of emission are representative obstacles for effective PDT. In this paper, three D-π-A structured PSs TSB-OH , TSBPy-OH , TSBPy-DNT with aggregation induced emission (AIE) properties and integrated type I and type II ROS generation were synthesized by modulating distinct acceptor units. Among them, TSBPy-OH is optimal with multiple advantages including near-infrared emission, good biocompatibility , remarkably intracellular ROS production ability, mitochondria targeting capability inducing cell apoptosis and enhancing PDT, and long-term tumor retention ability for imaging-guided photodynamic therapy. More importantly, efficient in vitro cancer cells damage, in vivo tumor ablation and ignorable damage in major organs during PDT are demonstrated, suggesting potential capability of TSBPy-OH in safe and effective fluorescence imaging-guided PDT. This successful example of AIE theranostics design would provide a reference for the modification of D-π-A structure organic AIEgens.
研究领域:
癌症治疗
·
光动力疗法
·
材料科学
·
生物医学工程
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yanmei Li,Junmei Nie,Xinyu Li,Ni Yan,Renjiang Kong,Jiaqi Huang,Yeyang Wu,Zhuofeng Li,Yingtao Zhong,Xin Chen,Hong Cheng
Stimulator of interferon genes (STING) plays an essential role in initiating the innate anti-tumor immunity, which could be activated by the cytosolic DNA but suppressed by the immunosuppressive cells. In this work, a self-delivery ternary immunostimulant (designated as ImmSt) is fabricated for colorectal cancer therapy with the immunological cascades of photodynamic DNA damage and T regulatory cell inhibition. Among which, the photosensitizer of Chlorin e6 (Ce6), the STING agonist of 5,6-dimethylxanthine-4-acetic acid (DMXAA) and the phosphatidylinositol 3-kinases (PI3Ks) inhibitor of ZSTK474 could self-assemble into uniform nanomedicine without drug excipient, which enhances the drug stability, bioavailability and pharmacological activities. Importantly, the photodynamic therapy (PDT) effect of ImmSt produces enormous reactive oxygen species to ablate tumor cells, and also triggers the release of cytosolic DNA to amplify the STING signal in combination with the STING agonist. Moreover, ImmSt is able to induce a systemic anti-tumor immunity by the cascade activation of T cells and the decrease of T regulatory cells. In vitro and in vivo results confirm that ImmSt can efficiently eradicate colorectal cancer without severe side effects, which may provide a sophisticated mechanism for immunotherapy in consideration of the immune activation and immunosuppressive factors.
研究领域:
肿瘤学
·
免疫疗法
·
药理学
·
纳米技术
·
分子生物学
✓ 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）