MOLECULAR PHARMACEUTICS
·
2016
·
IF 4.342
Ahu Yuan,Wei Huan,Xiang Liu,Zhicheng Zhang,Yifan Zhang,Jinhui Wu,Yiqiao Hu
Nanocarriers like PEGylated liposomes have achieved enhanced drug accumulation in tumors and reduced systemic side effects, but failed to actively release the carried drug into cancer cells. To obtain improved therapeutic efficacy, we designed a novel liposome that was inserted by the amphiphilic agent PEG-IR780-C13 (PIC-Lipo) and encapsulated therapeutic agent doxorubicin (DOX), termed as DOX@PIC-Lipo. Upon NIR laser irradiation, the novel liposomes could generate hyperthermia and facilitate the release of encapsulated DOX from PIC-Lipo, which were confirmed by photothermal curves and the DOX release assay in vitro, respectively. In addition, the enhanced DOX release and sufficient hyperthermia have performed synergetic therapeutic efficacy both in vitro and in vivo. Therefore, DOX@PIC-Lipo might provide an active strategy to release the loaded drug for synergetic chemo–photothermal combined therapy.
研究领域:
癌症治疗
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药剂学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Dawei Jiang,Luqi Pan,Xiao Yang,Zhixiao Ji,Cheng Zheng,Zhizhen Meng,Bin Liang,Weian Zhang,Jinfei Chen,Changcan Shi
The newly attractive peroxynitrite (ONOO − ) therapy can prominently enhance antibacterial therapeutic efficacy. However, it is a great challenge but urgently needed to generate ONOO − with adjustable release rate and dosage in order to satisfy personalized treatments for different disease types and severities. Herein, PSNO@IR780 nanoparticles are fabricated via co-assembly of an amphiphilic PEG- b -PAASNO block copolymer grafted with abundant nitric oxide (NO) donor units and IR780 as a photothermal and photodynamic agent. Photo-controllable burst generation of ONOO − from PSNO@IR780 nanoparticles could be realized based on synergistic reactions of rapid NO release induced by increased local temperature and efficiently produced superoxide anion radical (O 2 •− ) from IR780. The maximum ONOO − release dosage is up to 6.73 ± 0.07 µM and release rate is up to 98.1 ± 1.38 nM/s. Furthermore, the ONOO − release behavior can be precisely manipulated by varying sample concentrations, irradiated durations, output power densities, and laser switches, respectively. Ultra-efficiently generated ONOO − from biocompatible PSNO@IR780 nanoparticles significantly elevated broad spectrum antibacterial efficiency through damaging bacterial membranes . Thus, PSNO@IR780 nanoparticles may present a new insight into preparation of burst and controllable generating ONOO − materials, and provide new opportunities for antibacterial therapy. Statement of significance 1. Polymeric NO donor (PEG- b -PAASNO) grafted with abundant NO donor units was synthesized. 2. PSNO@IR780 nanoparticles were prepared by co-assembly of IR780 and amphiphilic PEG- b -PAASNOpolymer. 3. The maximum ONOO − release dosage from PSNO@IR780 nanoparticles was 6.73 ± 0.08 µM. 4. The fastest ONOO − release rate from PSNO@IR780 nanoparticles was 98.1 ± 1.4 nM/s. 5. Ultra-efficiently generated ONOO − significantly elevated antibacterial efficiency via damaging bac-terial membranes.
研究领域:
生物材料学
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药剂学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Xiaoqing Han,Xingbo Wang,Jiao Yan,Panpan Song,Yanjing Wang,Yaqing Kang,Abdur Rauf,Haiyuan Zhang
The large recruitment of tumor-associated macrophages and low exposure of tumor-associated antigens in tumor microenvironment have severely suppress the efficacy of anti-tumor immunotherapy. Herein, biosynthesized magnetosome (Mag) from bacteria was loaded with photothermal/photodynamic agent/near infrared (NIR) fluorescence dye (IR780) and further modified with lipid-PEG-c(RGDyK) through biomembrane, forming I Mag RGD for fluorescence imaging, magnetic resonance imaging, immunotherapy and photodynamic/photothermal therapy. After intravenous injection into B16F10 tumor-bearing mice, I Mag RGD could efficiently accumulate in tumor tissues based on near infrared (NIR) fluorescence and magnetic resonance dual-modality imaging, and repolarize tumor-associated macrophages (TAMs) from M2 phenotype to M1 phenotype, significantly improving the effect of tumor immunotherapy. Moreover, photothermal and photodynamic effect of IR780 could kill tumor cells and elicit immunogenic cell death to mediate anti-tumor immunity, promoting dendritic cells (DCs) maturation and then activating specific effector T cells to further eliminate tumor cells. This study provides a new approach for reversing the activity of tumor immunosuppressive microenvironment and strengthening the efficiency of tumor photoimmunotherapy.
研究领域:
肿瘤治疗
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生物材料
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免疫学
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分子影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 34
·28298-28312
·
IF 4.6
Fan Yang,Hongchi Liu,Qian Luo,Hao Deng,Rongrong Zhang,Yi Yang,Hong Yang,Huaying Wu,Xiaojun Tao
In this study, the amphiphilic polymer HA–ANI, formed by grafting hyaluronic acid (HA) and 6-(2-nitroimidazolyl)hexylamine (ANI), was self-assembled in water to form nanoparticles (NPs), which were modified to obtain dual drug-loaded nanoparticles (P/I NPs) by dialysis loading of paclitaxel (PTX) and IR780. Electron microscopy and dynamic light scattering (DLS) results showed that the P/I NPs presented a near-spherical shape with a size of 221.10 ± 2.31 nm. The drug loading and encapsulation rates of PTX in P/I NPs were 22.73% and 89.23%, respectively, and those of IR780 were 1.11% and 42.44%, respectively. In vitro release experiments demonstrated that NADPH could accelerate the drug release from the NPs. Under the irradiation of an NIR laser, the temperature of the P/I NPs increased significantly. In an in vitro cellular assay treating 4T1 cells for 24 h, the cellular uptake rate of NPs could reach 91.50 ± 3.51%, the 4T1 cell migration rate was 2.68 ± 0.34%, the cell viability was 39.96 ± 0.55%, and the apoptotic cell death rate was 13.93 ± 0.42%. In an in vivo anti-tumor experiment, the inhibition rate of the P/I NPs towards tumors was up to 35.44%; the fluorescence intensity at the tumor site gradually increased with time, and the maximum value appeared within 24 h, indicating that the P/I NPs had a targeting function. The results of H&E staining showed that there was no obvious pathological damage to the main organs of the mice in each group, that means there were no obvious side effects.
研究领域:
纳米医学
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肿瘤学
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药剂学
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生物化学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Zhou Yun,Lin Bixia,Li Kai,Zhao Yufeng,Sun Zhuo,He Chenchen,Jha Rajiv Kumar
At present, the clinical diagnosis of and treatment methods for hepatic carcinoma still fail to fully meet the needs of patients. The integrated theranostic system, in which functional materials are used to load different active molecules, created a new developmental direction for the combination treatment of hepatic carcinoma, realizing the synchronization of diagnosis and treatment. In this study, polydopamine (PDA), which has the functions of self-assembly, encapsulation, photothermal conversion, and photoacoustic interaction, was used as the carrier material. The IR780, a near-infrared fluorescence imaging (NIFI), photoacoustic imaging (PAI), and photothermal therapy (PTT) agent, and paclitaxel (PTX), a broad-spectrum chemotherapy drug, were selected to build the NIF/PA dual-mode imaging and PTT/chemo synergistic theranostic nanoparticles (DIST NPs). The DIST NPs have a 103.4 ± 13.3 nm particle size, a weak negative charge on the surface, good colloidal stability, slow and controlled drug release, and high photothermal conversion ability. The experiments results showed that the DIST NPs have a long circulation in vivo, high bioavailability, high biocompatibility, and low effective dose. DIST NPs showed an excellent NIFI/PAI dual-mode imaging and significant synergistic antitumor effect in hepatic carcinoma models. DIST NPs met the initial design requirements. A set of fast and low-cost preparation methods was established. This study provides an experimental basis for the development of new clinical theranostic methods for hepatic carcinoma.
研究领域:
纳米技术
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医学影像
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癌症治疗
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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
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Feiyang Xu,Ting Cui,Haidong Shen,Hongfu Liu,Jianfei Xie,Kai Yang,Yugui Tao
Multidrug-resistant (MDR) bacterial infections remain a critical public health concern worldwide, with conventional antibacterial strategies presenting limitations such as inconsistent target localization, suboptimal therapeutic efficiency, and progressive antimicrobial resistance development. Nitric oxide (NO), a bioactive molecule, exhibits potent antibacterial effects, resulting in the emergence of NO-based gas therapy as a promising and innovative therapeutic strategy. However, these therapies present the principal challenge of effective NO delivery, owing to its short half-life and limited diffusion capacity. Hence, this study aimed to develop AI‑molybdenum disulfide (L-Arg/IR780@MoS 2 ) nanoflowers (NFs) employing L-arginine (L-Arg) as an endogenous NO precursor and MoS 2 as a dual carrier for L-Arg and IR780 iodide (IR780). Following near-infrared irradiation during photodynamic therapy, generated reactive oxygen species initiated an oxidation cascade for L-Arg-to-NO conversion. The produced NO, in combination with photothermal therapy, modulated the bacterial microenvironment. This significantly altered the expression of key genes in MDR bacteria associated with nucleotide metabolism and biofilm formation, thereby effectively disrupting biofilms and suppressing bacterial growth. Furthermore, the AI-MoS 2 NFs exhibited notable ancillary therapeutic benefits, including anti-inflammatory activity, enhanced re-epithelialization, increased collagen deposition, and angiogenesis modulation, which collectively accelerated wound healing. Altogether, the findings of this study present a synergistic therapeutic strategy designed to address the dual challenges posed by bacterial biofilms and antimicrobial resistance.
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yuhan Wang,Chunyan Yue,Mengyao Zhang,Dazhao Li,Tao Xu,Mengying He,Mengyuan Wang,Yanan Zhao,Zihui Ni,Feng Zhi,Yiqiao Hu,Dawei Ding
Combining chemotherapy and phototherapy (including photodynamic therapy and photothermal therapy) via nanoscale drug delivery systems has been widely explored to improve the therapeutic efficacy of cancers. Nevertheless, deficient reactive oxygen species (ROS) level caused by the excessive antioxidants (e.g., glutathione (GSH)) in tumor cells and thermoresistance mediated by heat shock proteins (HSPs) represent two pivotal obstacles for phototherapy. In addition, limited control on drug release via conventional nanocarriers results in unpredictable side effects of chemotherapeutic drugs. To tackle these problems, a novel phase change material (PCM)-based nanoplatform co-delivering paclitaxel (PTX), IR780 and gambogic acid (GA) was developed via a facile method to achieve chemotherapy synergized by dually-enhanced phototherapy of breast cancers. PCM-based nanoparticles (NPs) revealed favorable particle size and greatly improved photostability of IR780. PCM endowed the NPs with hyperthemia-triggered release of PTX for chemotherapy, which was beneficial to dampen the side effects. Upon the cellular uptake, GA-depleted intracellular GSH and blocked the overexpression of HSP90, which in turn simultaneously increased the ROS level and suppressed thermoresistance to enhance the efficacies of PDT and PTT, respectively. Finally, the dually-energized phototherapy and PTT-activated low-dose PTX-based chemotherapy achieved outstanding antitumor performances in vitro and in vivo. Taken together, via the NIR-activatable PCM-based NPs, a strategy of harnessing a single enhancer to boost the efficacies of dual-modal phototherapy and low-dose chemotherapy has been established for improved cancer treatment and reduced side effects.
研究领域:
癌症治疗
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纳米技术
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药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yuao Feng,Zeliang Wu,Hui Liu,Rong Xu
Triple-negative breast cancer (TNBC) presents a formidable challenge due to its poorest prognosis and limited array of treatment options available. Photodynamic therapy (PDT) has emerged as a potent therapeutic modality to generate intratumoral toxic reactive oxygen species (ROS) in combating refractory triple-negative breast cancer (TNBC). However, its therapeutic efficacy is compromised due to insufficient tumor accumulation and therapeutic resistance. Herein, an “all-in-one” tumor-therapeutic nanomedicine named HA@IR780@KU55933@BSA (HIKB) which integrated photosensitizer IR780 with ATM kinase inhibitor KU55933 was designed to facilitate drug delivery and target specific pathways involved in tumor PDT treatment resistance. Co-delivery of IR780 and KU55933 exacerbated intracellular ROS production, mitochondrial dysfunction and DNA damage to form a potent anti-TNBC therapeutic cyclical feedback loop and then induced pyroptosis and apoptosis of TNBC cells by activating the Caspase3/GSDME signaling pathway and regulating apoptosis-related protein expression, respectively. In vivo evaluations in the TNBC orthotopic xenograft mouse model demonstrated that the designed HIKB NPs could accumulate in tumor tissues and exert synergistic therapeutic effects. Altogether, this study described a self-assembling strategy for constructing an all-in-one nanomedicine that effectively integrates multiple therapeutic modalities to provide a comprehensive and systemic approach to tumor suppression.
研究领域:
肿瘤学
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治疗学
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纳米技术
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癌症生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-13
·
IF 10.435
Zhang Gutian,Cheng Wenting,Du Lin,Xu Chuanjun,Li Jinlong
Background Phototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). However, the therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). In this study, we developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement. Results Near-infrared photosensitizer (IR780) and gambogic acid (GA, Hsp90 inhibitor) were encapsulated into albumin nanoparticles via hydrophobic interaction, which was further deposited MnO 2 on the surface to form IGM nanoparticles. Both in vitro and in vivo studies demonstrated that IGM could catalyze overexpress of hydrogen peroxide to relive hypoxic tumor microenvironment. With near infrared irradiation, the ROS generation was significantly increase for PDT enhancement. In addition, the release of GA was promoted by irradiation to bind with Hsp90, which could reduce cell tolerance to heat for PTT enhancement. As a result, IGM could achieve better antitumor efficacy with enhanced PDT and PTT. Conclusion This study develops a facile approach to co-deliver IR780 and GA with self-assembled albumin nanoparticles, which could relive hypoxia and suppress Hsp for clinical application of cancer phototherapy.
研究领域:
癌症治疗
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纳米技术
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光疗
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Kaiqing Yun,Juntong Guo,Renfang Zhu,Tianyi Wang,Xiaoyan Zhang,Hao Pan,Weisan Pan
Combining chemotherapy with photothermal therapy (PTT) for cancer treatment could overcome the inherent limitations of both single-modality chemotherapy and PTT. However, the obstacle of accurate drug delivery to tumor sites based on chemo-photothermal remains challenging. This article describes development of a reactive oxygen species (ROS)-responsive hyaluronic acid-based nanoparticle to overcome these drawbacks. Herein, HA-TK-MTX (HTM) was synthesized by a ROS-responsive cleaved thioketal moiety linker (TK) of methotrexate (MTX) and hyaluronic acid (HA). Through hydrophobic interaction and π–π stacking interaction, a photothermal agent IR780 was integrated into the HTM, and the IR780/HTM nanoparticles (IHTM NPs) were obtained. The IHTM NPs show high photostability, excellent photothermal performance, remarkable tumor-targeting ability, and ROS sensibility. Due to the accurate drug delivery ability and superior chemo-photothermal treatment effect of IHTM NPs, the tumor inhibition rate reached 70.95% for 4T1 tumor-bearing mice. This work serves as a precedent for the chemo-photothermal therapy of cancer by rationally designing ROS-responsive nanoparticles.
研究领域:
纳米技术
·
癌症研究
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药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Nan Zhang,Yang Tan,Liwei Yan,Chunyang Zhang,Ming Xu,Huanling Guo,Bowen Zhuang,Luyao Zhou,Xiaoyan Xie
Background and Purpose Sonodynamic therapy (SDT) has been widely used for the noninvasive treatment of solid tumors, but the hypoxic tumor microenvironment limits its therapeutic effect. The current methods of reoxygenation to enhance SDT have limitations, prompting reconsideration of the design of therapeutic approaches. Here, we developed a tumor microenvironment-responsive nanoplatform by reducing oxygen consumption to overcome hypoxia-induced resistance to cancer therapy.Methods A pH-responsive drug-loaded liposome (MI-PEOz-lip) was prepared and used to reduce oxygen consumption, attenuating hypoxia-induced resistance to SDT and thereby improving therapeutic efficiency. Photoacoustic imaging (PAI) and fluorescence imaging (FI) of MI-PEOz-lip were evaluated in vitro and in breast xenograft tumor models. The pH-sensitive functionality of MI-PEOz-lip was applied for pH-triggered cargo release, and its capacity was evaluated. The MI-PEOz-lip-mediated SDT effect was compared with other treatments in vivo.Results MI-PEOz-lip was demonstrated to specifically accumulate in tumors. Metformin molecules in liposomes selectively accumulate in tumors by pH-responsive drug release to inhibit the mitochondrial respiratory chain while releasing IR780 to the tumor area. These pH-responsive liposomes demonstrated PAI and FI imaging capabilities in vitro and in vivo, providing potential for treatment guidance and monitoring. In particular, the prepared MI-PEOz-lip combined with ultrasound irradiation effectively inhibited breast tumors by producing toxic reactive singlet oxygen species (ROS), while the introduction of metformin inhibited mitochondrial respiration and reduced tumor oxygen consumption, resulting in excellent sonodynamic therapy performance compared with other treatments.Conclusion In this study, we present a novel strategy to achieve high therapeutic efficacy of SDT by the rational design of multifunctional nanoplatforms. This work provides a new strategy that can solve the current problems of inefficient oxygen delivery strategies and weaken resistance to various oxygen-dependent therapies.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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药学
·
医学影像
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2020
·Vol. 18
·期 1
·1-13
·
IF 6.518
Zhu Guanchen,Wang Kaikai,Qin Haixiang,Zhao Xiaozhi,Chen Wei,Xu Linfeng,Cao Wenmin,Guo Hongqian
Background Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment. Methods The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated. Results The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment. Conclusion A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）