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Biomaterials Science · 2023 ·Vol. 11 ·期 14 ·4874-4889 · IF 6.6

Hollow silver–gold alloy nanoparticles for enhanced photothermal/photodynamic synergetic therapy against bacterial infection and acceleration of wound healing

Shanshan Lin,Hui Chen,Rui Wang,Tongmeng Jiang,Rui Wang,Fabiao Yu

Bacterial infection seriously restricts the wound healing process due to severe inflammation and delayed wound healing. Unfortunately, the overuse or improper use of antibiotics leads to the advent of multidrug-resistant strains and intractable biofilms, severely affecting the therapeutic effect. Therefore, there is an urgent need to develop antibiotic-free strategies to accelerate the healing process of wounds with bacterial infection. Considering that single photothermal therapy (PTT) or photodynamic therapy (PDT) cannot fully meet the requirements of clinical sterilization and accelerating wound healing, herein, hollow silver–gold alloy nanoparticles immobilized with the photosensitizer molecule Ce6 (Ag@Au-Ce6 NPs) integrated with PTT and PDT are proposed for killing bacteria and accelerating wound healing. The photothermal conversion properties of Ag@Au-Ce6 NPs are obtained using an infrared thermal imager, and the generation of singlet oxygen (1O2) is verified with an 1O2 fluorescent probe DCFH-DA. Manipulated by near-infrared laser triggered mild hyperthermia and limited ROS amount, Ag@Au-Ce6 NPs could effectively kill bacteria that are free and colonized on the surface of wounded skin, promoting epithelium migration and vascularization, further accelerating wound healing, which showed great promise for biomedical application.

研究领域: 纳米技术 · 生物医学工程 · 光疗 · 伤口愈合 · 抗菌治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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RSC Advances · 2023 ·Vol. 13 ·期 6 ·3459-3467 · IF 3.9

Liposomes loaded with dual clinical photosensitizers for enhanced photodynamic therapy of cervical cancer

Gulinigaer Alimu,Ting Yan,Lijun Zhu,Zhong Du,Rong Ma,Huimin Fan,Shuang Chen,Nuernisha Alifu,Xueliang Zhang

Photodynamic therapy (PDT) has become a potential anti-cancer strategy owing to its negligible invasiveness, low toxicity, and high selectivity. The photosensitizer (PS) plays an indispensable role in PDT. Herein, a novel type of PS (Ce6-MB@Lips) which can be excited by a near-infrared (NIR) laser was designed and synthesized. Methylene blue (MB) and Chlorin e6 (Ce6), two organic dyes approved by the Food and Drug Administration (FDA), were used to prepare Ce6-MB@Lips by thin-film dispersion method, which improve the water solubility of Ce6 and reduce the cytotoxicity of MB. The Ce6-MB@Lips were shown to have a spherical nanostructure with an average particle size of 160.3 nm and excellent water solubility. Then the optical properties of Ce6-MB@Lips were further studied. Ce6-MB@Lips showed absorption peaks at 413 nm/670 nm and fluorescence peak at 697 nm. Compared with Ce6@Lips and MB@Lips, Ce6-MB@Lips showed better stability, stronger fluorescence intensity, and higher singlet oxygen (1O2) generation ability. Cell experimental analysis exhibited that the stable Ce6-MB@Lips showed low cytotoxicity, high phototoxicity and high reactive oxygen species (ROS) production capacity. After effective cell internalization, the prepared Ce6-MB@Lips showed excellent ability to promote tumor cell apoptosis in vitro. The Ce6-MB@Lips could be a promising candidate for PDT of cervical cancer.

CAS / MDL: 7220-79-3 61-73-4
研究领域: 肿瘤学 · 药学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Small · 2021 ·Vol. 17 ·期 10 ·2007953 · IF 13.281

Dual-Channel Theranostic System for Quantitative Self-Indication and Low-Temperature Synergistic Therapy of Cancer

Cheng Wang,Shaoqing Chen,Fangying Yu,Jianghong Lv,Rui Zhao,Fuqiang Hu,Hong Yuan

A conventional theranostic system usually employs a single fluorescence channel to show the pharmacokinetic events, which usually fails to quantitatively reveal the true cumulative drug release and with low accuracy. Herein, indocyanine green (ICG) and chlorins e6 (Ce6) are selected not only as conventional photothermal/photodynamic agents, but also to offer two independent fluorescence channels to cross validate the authenticity of pharmacokinetic events and to quantitatively reveal cumulative drug release in tumor tissues in a “turn on” manner. Employing the Ca 2+ of amorphous calcium carbonate as a reversible linker, the photosensitivity and fluorescence of Ce6 are physically quenched by ICG during circulation to reduce the side effect of photodynamic therapy (PDT) while being readily restored in tumor tissue to reveal the quantitative drug release. Most importantly, the combination of photothermal therapy (PTT) and PDT allows low-temperature synergistic therapy of cancer through the controlled expression of heat shock protein in cells and mild hyperthermia enhanced reactive oxygen species diffusion/penetration among cells. This work not only develops a facile approach to fabricate a dual-channel theranostic system to precisely indicate the accumulation and quantitative drug release in tumor tissue, but also presents a unique low-temperature synergistic strategy to destroy tumor in an effective and minimally invasive manner.

CAS / MDL: 1306-38-3 3599-32-4
研究领域: 癌症治疗 · 生物医学工程 · 药学 · 纳米技术 · 诊疗学
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY · 2023 · IF 6.7

“Domino” cascade reactor based on DNA hydrogel for synergistic treatment of malignant tumor

Xiaofan Liu,Minghui Ma,Shuo Tian,Weicai Wang,Xuemei Li

The action pathways of starvation therapy and photodynamic therapy (PDT) do not exist in isolation and are usually related to tumor cell metabolism and immune regulation, which are of great significance in the treatment of malignant tumors. Here, a cancer-targeted “domino” cascade reactor is constructed for synergistic starvation therapy and amplifies photodynamic therapy by assembling hemin and glucose oxidase (GOx) into DNA hydrogel load with hypoxia-inducible factor 1α (HIF-1α) and photosensitizer chlorin e6 (Ce6). The cascade reactor has excellent biocompatibility and tumor targeting, which promotes PDT by reducing HIF-1α. At the same time, the G-quadruplex of AS1411 combined with hemin (AH) catalyzes the generation of oxygen from hydrogen peroxide to further improve the efficiency of PDT. The synergistic therapeutic effect of the cascade reactor is evaluated through in vivo and in vitro experiments, indicating that this cascade reactor has great potential advantages in the synergistic treatment of cancer.

CAS / MDL: 7727-54-0 67-68-5
研究领域: 生物医学工程 · 癌症治疗 · 纳米技术 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMATERIALS · 2020 · IF 10.317

Light-assisted hierarchical intratumoral penetration and programmed antitumor therapy based on tumor microenvironment (TME)-amendatory and self-adaptive polymeric nanoclusters

Jing Yan,Qinghua Wu,Ziyin Zhao,Jianhua Wu,Huan Ye,Qiujun Liang,Zhuchao Zhou,Mengying Hou,Xudong Li,Yong Liu,Lichen Yin

The anticancer performance of nanomedicine is largely impeded by insufficient intratumoral penetration. Herein, tumor microenvironment (TME)-amendatory and self-adaptive nanoclusters (NCs) capable of cancer-associated fibroblasts (CAFs) depletion and size/charge conversion were engineered to mediate light-assisted, hierarchical intratumoral penetration. Particularly, large-sized NCs (~50 nm) were prepared via self-assembly of FAP-α-targeting peptide-modified, 1 O 2 -sensitive polymers, which were further used to envelope small-sized dendrimer (~5 nm) conjugated with Ce6 and loaded with DOX (DC/D). After systemic administration, the NCs efficiently targeted CAFs and generated lethal levels of 1 O 2 upon light irradiation, which depleted CAFs and concomitantly dissociated the NCs to liberate small-sized, positively charged DC/D. Such stroma attenuation and NCs transformation collectively facilitated the delivery of DC/D into deeper regions of CAF-rich tumors, where DOX and 1 O 2 provoked synergistic anti-cancer efficacies. This study provides an effective approach to facilitate the tumor penetration of nanomedicine by concurrently and spatiotemporally reconfiguring the nano-properties and remodeling the TME.

研究领域: 纳米技术 · 癌症治疗 · 药学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Nano Materials · 2022 · IF 6.14

Hollow MnO2 Nanoparticles Loaded with Functional Genes as Nanovaccines for Synergistic Cancer Therapy

Weicai Wang,Xiaozu Chen,Junwei Li,Qiu Jin,Hyung Jong Jin,Xuemei Li

Nanotechnology provides more developments and challenges for cancer immunotherapy. Nanomaterial-mediated synergistic therapy, immunosuppressive adjustment of the tumor microenvironment (TME), and nanovaccine construction can promote cancer immunotherapy. Here, based on the biodegradable hollow manganese dioxide (H-MnO2) tumor-targeted drug delivery platform, we have developed a TME-responsive nanovaccine for synergistic cancer therapy. The nanoplatform significantly enhanced photodynamic therapy (PDT)-mediated immune response by improving the hypoxic tumor microenvironment and on-demand drug release. At the same time, it was supplemented with gene therapy and chemotherapy to achieve significant in vivo combined therapy benefits. Taking full advantage of the high reactivity to the hydrogen peroxide and weak acidity of the TME, H-MnO2 loaded with chemotherapy drug doxorubicin (DOX) and photosensitizer chlorin e6 (Ce6) not only provided the required oxygen for photodynamic therapy but also reduced the side effects of chemotherapy drugs on normal tissues. Moreover, the coating of nucleic acid on H-MnO2 solved the problem of biocompatibility of nanoparticles and ensured that they could be swallowed by cancer cells. The results revealed that through the controlled release of targeted drugs and combined therapy, the synergistic nanovaccine significantly inhibited tumor growth in mice, which is expected to achieve the treatment of primary tumors.

研究领域: 纳米技术 · 癌症免疫治疗 · 药物递送系统 · 光动力疗法 · 基因治疗 · 化疗 · 生物相容性
✓ 已验证 DOI 高影响因子
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ACS Applied Nano Materials · 2023 · IF 5.9

Multifunctional ZnFeO4-Based Antibiotic Cross-Linked Nanoplatform for Magnetically Targeted Treatment of Microbial Biofilms

Xingyue Yang,He Ren,Jiexin Li,Boyang Sun,Di Lu,Shuying Li,Yumiao Zhang

During the infections of wounds or medical device surfaces, bacteria such as Pseudomonas aeruginosa are prone to forming biofilms which prevent the penetration of antimicrobial agents. Herein, a combined therapy using bactericidal nano-micelles Ce6-ZnFeO4@ABCsi-micelles was developed that employed colistin cross-linked Pluronic micelles as a carrier, with the magnetic metal oxide ZnFeO4 and photosensitizer dihydroporphyrin (Ce6) encapsulated in the core of micelles. Driven by an external magnetic field, the nano-micelles could penetrate the external barrier of the biofilm. Reactive oxygen species (ROS) generated by the photosensitizer Ce6 disrupted the barrier of the biofilm, which facilitated the distribution of the Ce6 and colistin antibiotics into the biofilm, realizing a 99.5% clearance rate of bacteria. Using such a combination of chemotherapy and photodynamic therapy, Ce6-ZnFeO4@ABCsi-micelles could clear wound infection in a murine abscess model, owing to the targeted driving effect of the external magnetic field, along with the chemotherapeutic effect of colistin and the photodynamic effect of Ce6. This design provides an effective targeted therapeutic strategy to address biofilm infections.

CAS / MDL: 9002-18-0
研究领域: 纳米技术 · 生物医学工程 · 微生物学 · 药学 · 传染病学
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Materials Today Nano · 2023 · IF 10.3

Enhancing catalase-like activity of Prussian blue nanozyme by gadolinium-doping for imaging-guided antitumor amplification via photodynamic therapy and chemotherapy

H. Wang,Y. Shen,L. Chen,K. Li,Y. Shi,Z. Xu,D. Li,H. Chen,W. Wang,L. Gao

Deprivation of O 2 in most solid tumors greatly limits the effectiveness of photodynamic therapy. Prussian blue nanozyme (PBzyme) are reported to possess catalase-like (CAT) activity to alleviate tumor hypoxia . However, the low catalytic activity is far from satisfactory. Metal doping may improve the catalytic activity of PBzyme, but there are few reports in this regard. Herein, by a screening of metal dopants , Gd-doped PB with enhanced CAT activity is constructed on the basis of small-sized hollow mesoporous silica nanoparticles . Theoretical calculation demonstrates that Gd regulates the state density population of Fe in PBzyme and reduces the Gibbs free energy of CAT catalytic cycle, thus improving its CAT activity (approximately 4 times higher than that of pure PBzyme). After conjugated with photosensitizer Ce6 and tumor-targeted molecule folic acid and loaded with chemotherapy drug doxorubicin , the nanoplatform displays dual-enhanced T 1 and T 2 imaging capacity simultaneously. Upon high accumulation in tumors, the nanoplatform demonstrates augmented antitumor effects by combining enhanced photodynamic therapy and doxorubicin-mediated chemotherapy both in vitro and in vivo . This work demonstrates that the integration of Gd into PBzyme is an effective strategy to improve the catalytic activity of PBzyme and further potentiate the effectiveness of tumor theranostics.

CAS / MDL: 9002-93-1
研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 材料科学 · 分子生物学 · 医学成像
✓ 已验证 产品关联 DOI 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2020 · IF 7.727

Photo-triggered self-destructive ROS-responsive nanoparticles of high paclitaxel/chlorin e6 co-loading capacity for synergetic chemo-photodynamic therapy

Xiaoye Yang,Xiaoqun Shi,Yanan Zhang,Jiangkang Xu,Jianbo Ji,Lei Ye,Fan Yi,Guangxi Zhai

To improve the anti-cancer therapeutic effect of nanosystems for chemo-photodynamic therapy, there remain several hurdles to be addressed, e.g. , limited co-loading efficiency, insufficient stimulus-responsiveness and lack of synergetic effect. This work reported novel reactive‑oxygen-species (ROS)-responsive chlorin e6 (Ce6) and paclitaxel (PTX) co -encapsulated chondroitin sulfate- g -poly (propylene sulfide) nanoparticles (CP/ChS- g -PPS NPs), wherein the drug loading efficiencies of Ce6 and PTX were as high as 14.93% and 24.31%, respectively. To enlarge the ROS signal at tumor sites thus enhancing the ROS-responsiveness of ChS- g -PPS NPs, near-infrared (NIR) light was utilized to induce Ce6 to produce more ROS to destruct the NPs. Our data showed that the photo-triggered self-destructive property of NPs helped drugs to spread deeper in tumors upon laser irradiation, making the NPs promising to thoroughly remove tumor cells. CP/ChS- g -PPS NPs exhibited a synergetic chemo-photodynamic therapy effect in vitro , which was suggested by the combination indexes of PTX and Ce6 lower than 1 when 20–80% inhibition rates of MCF-7 cells were achieved. As for the in vivo antitumor activity , the tumor inhibition rates of CP/ChS- g -PPS NPs (with laser irradiation) were as high as 92.76% and 88.57% in 4T1 bearing BALB/c mice and MCF-7 bearing BALB/c nude mice, respectively, which were significantly higher than those of other treatment groups. This work provided a simple yet effective strategy to develop photo-triggered ROS-responsive NPs for synergetic chemo-photodynamic therapy with quick ROS-responsive self-destruction, spatiotemporally controllability, reduced off-target toxicity, and desirable therapeutic effect.

研究领域: 药学 · 纳米技术 · 癌症治疗 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-18 · IF 10.6

Iron-based MOF with Catalase-like activity improves the synergistic therapeutic effect of PDT/ferroptosis/starvation therapy by reversing the tumor hypoxic microenvironment

Chen Yukun,Chen Yuanyuan,Wang Zhenzhi,Yang Lian,Zhang Yu,Zhang Zhanxia,Jia Lijun

Reversing the hypoxic microenvironment of tumors is an important method to enhance the synergistic effect of tumor treatment. In this work, we developed the nanoparticles called Ce6@HGMOF, which consists of a photosensitizer (Ce6), glucose oxidase (GOX), chemotherapy drugs (HCPT) and an iron-based metal-organic framework (MOF). Ce6@HGMOF can consume glucose in tumor cells through “starvation therapy”, cut off their nutrition source, and produce gluconic acid and hydrogen peroxide (H 2 O 2 ). Utilizing this feature, Ce6@HGMOF can produce oxygen through catalase-like catalytic activity, thereby reversing the hypoxic microenvironment of tumors. This strategy of changing the hypoxic environment can help to slow down the growth of tumor blood vessels and improve the drug-resistant microenvironment to some extent. Meanwhile, increasing the supply of oxygen can enhance the effect of photodynamic therapy (PDT) and enhance the oxidative stress damage caused by reactive oxygen species (ROS) in tumor cells. On the other hand, cancer cells usually produce higher levels of glutathione (GSH) to adapt to high oxidative stress and protect themselves. The Ce6@HGMOF we designed can also consume GSH and induce ferroptosis of tumor cells through Fenton reaction with H 2 O 2 , while enhancing the effect of PDT. This innovative synergistic strategy, the combination of PDT/ferroptosis /starvation therapy, can complement each other and enhance each other. It has great potential as a powerful new anti-tumor paradigm in the future.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 药学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nanoscale · 2018 ·Vol. 10 ·期 20 ·9707-9719 · IF 7.233

Charge-switchable nanocapsules with multistage pH-responsive behaviours for enhanced tumour-targeted chemo/photodynamic therapy guided by NIR/MR imaging

Jia Zhou,Tianliang Li,Chunlei Zhang,Junyuan Xiao,Daxiang Cui,Yingsheng Cheng

Multifunctional nanoplatforms have been developed into advanced drug delivery systems for cancer therapy. In this study, we report a charge-switchable nanocapsule with multistage pH-responsive behaviors. First, DOX-encapsulated and oleylamine-embedded hollow structures with a diameter of 132 ± 21 nm are prepared via the double emulsion method. Subsequently, the hollow structures are encompassed by Gd-DTPA-, chlorin e6 (Ce6)-, and folate (FA)-modified BSA to form tumour-targeted, dual NIR/MR imaging-guided and chemo–photodynamic therapeutic nanoplatforms. Importantly, the nanocapsule can intelligently switch its surface charge to positive under mildly acidic conditions (pH 6.5) with no release of Ce6 and DOX, which is confirmed by ξ-potential and cumulative release measurements. Moreover, confocal imaging pictures demonstrate that acid-sensitive DOX sealed in nanocapsules is progressively released into the nuclei of MGC-803 cells. These advantages as well as FA-targeting facilitate effective endocytosis and synergistic therapeutic efficacy. Selective tumour accumulation and long tumour retention time are further indicated by NIR/MR in vivo imaging. In addition, excellent therapeutic efficacy combined with chemotherapy (DOX) and photodynamic therapy (PDT) is observed with the tumour eventually ablating at the 15th day. All results demonstrate that the as-prepared nanocapsules hold great potential for clinical cancer theranostics.

研究领域: 癌症治疗 · 药物递送系统 · 纳米技术 · 成像技术 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomaterials Science · 2021 ·Vol. 9 ·期 22 ·7456-7470 · IF 6.843

A metformin-based nanoreactor alleviates hypoxia and reduces ATP for cancer synergistic therapy

Xiangyu Meng,Jia Song,Yunfeng Lei,Xuezhong Zhang,Zhixin Chen,Zhuoxuan Lu,Liming Zhang,Zhifei Wang

Severe hypoxia in solid tumors limits the efficacy of oxygen (O2)-dependent photodynamic therapy (PDT). The overexpressed heat shock proteins (HSPs) in tumor cells hamper the effect of photothermal therapy (PTT). Herein, a tumor oxygenation-enhanced and ATP-reduced gelatin nanoreactor (MCGPD ∼ RGD NPs) for PDT/PTT-augmented combination cancer therapy is reported. In this nanosystem, the Arg-Gly-Asp (RGD) peptides of MCGPD ∼ RGD NPs can ensure accurate recognition and sufficient accumulation in the tumor site. After accumulation, doxorubicin (DOX) can be released from MCGPD ∼ RGD NPs in a mild acidic tumor microenvironment (TME) for highly efficient chemotherapy. Upon 808 nm laser irradiation, the overexpressed matrix metalloproteinase-2 (MMP-2) in the TME and the heat produced from the PDA coating trigger Gel NP degradation to expose chlorin e6 (Ce6) and Met from the cavity of MCGPD ∼ RGD NPs. The exposed Met elevates the O2 content and reduces ATP production in tumor sites to spur the successful O2-dependent PDT and HSP-mediated PTT. The heat generated by the PDA coating directly kills the tumor cells to ensure PTT and amplifies the chemotherapeutic effect. In vitro and in vivo assays indicate that MCGPD ∼ RGD NPs have excellent ability to promote cell apoptosis and to inhibit tumor growth. Overall, this smart responsive hydrogel nanosystem with hypoxia-relieving capacity and ATP-decreasing performance provides a promising strategy against cancer.

CAS / MDL: 25316-40-9 1115-70-4
研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 药学
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