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ACS Nano · 2021 · IF 15.881

Cancer-Erythrocyte Hybrid Membrane-Camouflaged Magnetic Nanoparticles with Enhanced Photothermal-Immunotherapy for Ovarian Cancer

Jiaqiang Xiong,Meng Wu,Jilei Chen,Yaofa Liu,Yurou Chen,Guanlan Fan,Yanyan Liu,Jing Cheng,Zhenhua Wang,Shixuan Wang,Yi Liu,Wei Zhang

Cell-membrane-coated nanoparticles are widely studied due to their inherent cellular properties, such as immune escape and homologous homing. A cell membrane coating can also maintain the relative stability of nanoparticles during circulation in a complex blood environment through cell membrane encapsulation technology. In this study, we fused a murine-derived ID8 ovarian cancer cell membrane with a red blood cell (RBC) membrane to create a hybrid biomimetic coating (IRM), and hybrid IRM camouflaged indocyanine green (ICG)-loaded magnetic nanoparticles (Fe3O4-ICG@IRM) were fabricated for combination therapy of ovarian cancer. Fe3O4-ICG@IRM retained both ID8 and RBC cell membrane proteins and exhibited highly specific self-recognition of ID8 cells in vitro and in vivo as well as a prolonged circulation lifetime in blood. Interestingly, in the bilateral flank tumor model, the IRM-coated nanoparticles also activated specific immunity, which killed homologous ID8 tumor cells but had no effect on B16-F10 tumor cells. Furthermore, Fe3O4-ICG@IRM showed synergistic photothermal therapy, resulting in the release of whole-cell tumor antigens by photothermal-induced tumor necrosis, which further enhanced antitumor immunotherapy for primary tumor and metastatic tumor by activating CD8+ cytotoxic T cells and reducing regulatory Foxp3+ T cells. Together, the biomimetic Fe3O4-ICG@IRM nanoparticles showed synergistic photothermal-immunotherapy for ovarian cancer.

CAS / MDL: 9002-98-6
研究领域: 纳米技术 · 肿瘤学 · 生物医学工程 · 药学
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MOLECULAR PHARMACEUTICS · 2021 · IF 4.939

ICG/l-Arginine Encapsulated PLGA Nanoparticle-Thermosensitive Hydrogel Hybrid Delivery System for Cascade Cancer Photodynamic-NO Therapy with Promoted Collagen Depletion in Tumor Tissues

Zhiting Sun,Xiaoxiao Wang,Jing Liu,Zhihong Wang,Weiwei Wang,Deling Kong,Xigang Leng

Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. Specifically, the NO donor l-arginine (l-Arg) and the photosensitizer indocyanine green (ICG) were co-encapsulated in poly(lactic-glycolic acid) (PLGA) nanoparticles and then loaded into the poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL–PEG–PCL) hydrogel to develop an injectable, thermosensitive dual drug delivery system (PLGA@ICG@l-Arg/Gel). Significantly, reactive oxygen species (ROS) produced by PLGA@ICG@l-Arg/Gel under near-infrared (NIR) light irradiation could not only result in the apoptosis of cancer cells but also oxidize l-Arg to generate NO, which could suppress the proliferation of cancer cells. Moreover, ROS could further oxidize NO to generate peroxynitrite anions (ONOO–). ONOO– could activate matrix metalloproteinases (MMPs), which notably degraded collagen in ECM so as to damage the tumor microenvironment. PLGA@ICG@l-Arg/Gel significantly increased the antitumor efficacy against highly malignant 4T1 tumors in mice. Taken together, PLGA@ICG@l-Arg/Gel is a multifunctional platform that provides a novel strategy for cancer treatment with cascade amplification of the ROS oxidation effect, which holds great potential in clinical translation.

CAS / MDL: 3599-32-4 301-10-0
研究领域: 癌症治疗 · 药物递送系统 · 材料科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioactive Materials · 2022 · IF 16.874

Pt(IV) prodrug initiated microparticles from microfluidics for tumor chemo-, photothermal and photodynamic combination therapy

Qingfei Zhang,Xiaocheng Wang,Gaizhen Kuang,Yuanjin Zhao

Multimodal treatment modalities hold great potential for cancer therapy, thus current efforts are focusing on the development of more effective and practical synergistic therapeutic platforms. Herein, we present a novel trans, trans,trans -[Pt(N 3 ) 2 (OH) 2 (py) 2 ] (Pt(IV)) prodrug-initiated hydrogel microparticles (M ICG-Pt ) with indocyanine green (ICG) encapsulation by microfluidics for efficiently synergistic chemo-, photothermal (PTT) and photodynamic therapy (PDT). The employed Pt(IV) could not only serves as an initiator to generate azidyl radical (N 3 • ) for photo-polymerization of methacrylate gelatin (GelMA) matrix, but also be reduced to high cytotoxic platinum(II) (Pt(II)) species for tumor chemotherapy. The laden ICG with highly photothermal heating ability and intrinsic reactive oxygen species (ROS) productivity endows the M ICG-Pt with effective PTT/PDT performances upon near-infrared (NIR) light irradiation. In addition, benefiting from the production of oxygen during the photo-activation process of Pt(IV), the PDT efficacy of ICG-laden M ICG-Pt could be further enhanced. Based on these advantages, we have demonstrated that the M ICG-Pt could significantly eliminate cancer cells in vitro , and remarkably suppressed the tumor growth in vivo via synergistic chemotherapy, PTT, and PDT. These results indicate that such Pt(IV)-initiated hydrogel microparticles are ideal candidates of multimodal treatment platforms, holding great prospects for cancer therapy.

研究领域: 癌症治疗 · 药学 · 材料科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NANOTECHNOLOGY · 2026 ·Vol. 37 ·期 12 ·125102 · IF 2.9

Construction of dunaliella salina-derived exosome-like nanovesicles co-delivery system for ICG and 5-FU and its enhanced suppression in triple-negative breast cancer cell

Junling An,Zequn Zhang,Xinwei Zhao,Yuanyuan Lv,Yantao Xu,Gaofeng Liang

A common strategy in cancer therapy involves using a nanoscale carrier to simultaneously deliver phototherapeutic agents and chemotherapeutic drugs. However, traditional delivery carriers are toxic and immunogenic, and their preparation involves complex procedures, limiting their widespread application. Exosomes, are spherical, lipid bilayer vesicles ranging from 50 to 150 nm in diameter, which are naturally secreted by various cells, and can cross various biological barriers, making them attractive alternatives. Dunaliella salina-derived exosome-like nanovesicles (DENVs) represent promising drug nanocarriers owing to their favorable bio-compatibility, low immunogenicity, cost-effective, large-scale, and rapid production. However, the role of DENV in triple-negative breast cancer (BC) remains unknown. In this study, DENV were prepared by ultracentrifugation. Indocyanine green (ICG) and 5-fluorouracil (5-FU) were co-loaded into DENV (DENV-ICG/5-FU) via electroporation. DENV-ICG/5-FU exhibited good photothermal performance and stability. At a pH of 5.0 and exposure to 808 nm near-infrared (NIR) light (1 W cm−2, 5 min), the cumulative release of 86.45% for 5-FU from the DENV-ICG/5-FU was observed. In addition, DENV-ICG/5-FU was internalized into 4T1 cells. Under NIR irradiation, it inhibited proliferation and migration and induced apoptosis of 4T1 cells. Results from flow cytometry and DCFH-DA analyses indicated that NIR irradiation markedly elevated both the percentage of cells in the G1 phase and the generation of reactive oxygen species. Mechanistic studies showed that under NIR irradiation, DENV-ICG/5-FU enhanced the expression of the pro-apoptotic protein Bax. In conclusion, these findings suggest that DENV could be ideal vehicles to co-deliver phototherapeutic agents and chemotherapeutic drugs for synergistic tumor treatment.

✓ 已验证 DOI 高影响因子
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NEW JOURNAL OF CHEMISTRY · 2021 ·Vol. 46 ·期 4 ·1569-1576 · IF 3.591

In situ formation of a near-infrared controlled dual-antibacterial platform

Zhuoyao Ni,Jiajie Hu,Hui Zhu,Yazhuo Shang,Daijie Chen,Yinghong Chen,Honglai Liu

Antibiotic resistance caused by long-term abuse of antibiotics has inevitably become a very serious problem and developing novel strategies to enhance the efficacy of treatments is exigent. Herein, a dual-antibacterial platform using sodium alginate (SA) and carboxymethyl chitosan (CMCS) as the framework was designed for NIR controlled pharmacotherapy and photothermal therapy of drug-resistant bacteria. The SA/CMCS solution can quickly transform into a hydrogel in response to Ca2+ and Mg2+ in biological bodies. By mixing indocyanine green (ICG) and thermosensitive drug-loaded liposomes into the solution, this designed platform can not only achieve near-infrared (NIR) controlled drug release properties but also possess dual-antibacterial capacity by combining pharmacotherapy and photothermal therapy (PTT). Local temperature rise induced by ICG will break the stability of thermosensitive liposomes, causing the release of the encapsulated drug. The in vitro antibacterial test and in vitro cytotoxicity experiment demonstrate the excellent antibacterial capacity and satisfactory biocompatibility of the prepared platform. The proposed NIR controlled dual-antibacterial platform can not only avoid bacterial resistance but also kill drug-resistant bacteria efficiently, which will provide a novel concept for the development of an intelligent antibacterial platform.

CAS / MDL: 83512-85-0
研究领域: 药学 · 生物医学工程 · 材料科学
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INORGANIC CHEMISTRY COMMUNICATIONS · 2024 · IF 4.4

Synthesis of drug-loaded H-ZIF-8@CaCO3-PEG nanocarrier for synergistic therapy

Han Song,Jiasheng Fan,Shengkai Liu,Boyu Chen,Jin Huang,Yujie Fu,Zhiguo Liu

In this study, we synthesized DOX-loaded H-ZIF-8@CaCO 3 -PEG nanocarrier, which combined with calcium overload and photothermal therapy (PTT) for synergistic therapy. The nanocarrier comprised a PEG modified calcium carbonate (CaCO 3 ) shell and a hollow imidazolate zeolite skeleton (H-ZIF-8) core, in which the chemotherapy drug doxorubicin hydrochloride (DOX) and photosensitizer indocyanine green (ICG) were simultaneously co-loaded. In vitro cellular experiments revealed that the lethality of DOX&ICG@H-ZIF-8@CaCO 3 -PEG against tumor cells was significantly higher than that of the single chemotherapy owing to the combination with chemotherapy and photothermal therapy as well as calcium overloading. This drug-loaded nanocarrier exhibits notable characteristics such as exceptional stability, elevated drug loading capacity and efficient release of the loaded drug, which provides a promising perspective for efficient synergistic therapy.

研究领域: 纳米技术 · 药学 · 癌症治疗
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Theranostics · 2020 · IF 8.579

In situ tumor-triggered subcellular precise delivery of multi-drugs for enhanced chemo-photothermal-starvation combination antitumor therapy

Xinglu Jiang,Xiaobo Fan,Rui Zhang,Wei Xu,Hailu Wu,Fengfeng Zhao,Han Xiao,Chen Zhang,Chenggui Zhao,Guoqiu Wu

Rationale: Drug combination therapy for cancer treatment exerts a more potent antitumor effect. The targeted delivery and release of multiple drugs in a patient's body thus presents a more effective treatment approach, warranting further research. Methods: Two antitumor drugs (ICG: indocyanine green and THP: pirarubicin) were successfully screened to sequentially trigger self-assembling peptides (P60) to produce bacteria-sized particles (500-1000 nm, P60-ICG-THP). First, after mixing equal amount of P60 and ICG, trace amount of water (the mass ratio between P60 and water: 100:1) was used to trigger their assembly into P60-ICG. Subsequently, the assembly of P60-ICG and THP was further triggered by ultrasound treatment to produce P60-ICG-THP. Results: P60-ICG-THP constituted a cluster of several nanoparticles (50-100 nm) and possessed a negative charge. Owing to its size and charge characteristics, P60-ICG-THP could remain outside the cell membrane, avoiding the phagocytic clearance of blood and normal tissue cells in vivo . However, after localizing in the tumor, the size and charge switches of P60-ICG-THP, rapidly triggered by the low pH of the tumor microenvironment, caused P60-ICG-THP to segregate into two parts: (i) positively charged nanoparticles with a size of approximately 50 nm, and (ii) negatively charged particles of an uneven size. The former, mainly carrying THP (chemotherapeutic agent), could immediately cross the cell membrane and deliver pirarubicin into the nucleus of tumor cells. The latter, carrying ICG (used for photothermal therapy), could also enter the cell via the endocytosis pathway or accumulate in tumor blood vessels to selectively block the supply of nutrients and oxygen (cancer starvation). Both these particles could avoid the rapid excretion of ICG in the liver and were conducive to accumulation in the tumor tissue for photothermal therapy. Conclusion: Our drug delivery system not only achieves the precise subcellular delivery of two anticancer drugs due to their size and charge switches in the tumor site, but also provides a new strategy to combine chemotherapy, photothermal therapy, and cancer starvation therapy for the development of a highly efficient antitumor therapeutic regimen.

研究领域: 肿瘤学 · 药理学 · 纳米技术 · 生物医学工程 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2022 · IF 11.467

A mutually beneficial macrophages-mediated delivery system realizing photo/immune therapy

Xiudan Wang,Junya Lu,Yuling Mao,Qinfu Zhao,Caishun Chen,Jianan Han,Meiqi Han,Huijuan Yuan,Siling Wang

The accumulation of nanomedicines in tumor tissues determines their therapeutic efficacy. We herein exploit the tropism of macrophages to improve the accumulation and retention time of nanomedicine at tumors. Interestingly, macrophages are not merely as transporters, but killers activated by nanomedicine. The system( [email protected] /ICG) was established by decorating macrophages with hyaluronic acid-modified hollow mesoporous carbon (C) nanoparticles loading indocyanine green (ICG). Notably, C nanoparticles with superior photothermal conversion capability not merely guarantee the efficient delivery of ICG through high drug loading efficiency and inhibiting the premature leaky, but effectually activate the polarization of macrophages. The results exhibited that those activated macrophages could release pro-inflammatory cytokines (NO, TNF-α, IL-12), while [email protected] /ICG afforded about 2-fold higher tumor accumulation compared with pure nanoparticle C-HA/ICG and produced heat and singlet oxygen ( 1 O 2 ) under irradiation of an 808  nm laser , realizing the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and cytokines-mediated immunotherapy . Specially, we also investigated the relationship of singlet oxygen ( 1 O 2 ) or temperature and tumor-killing activity for understanding the specific effectual procedure of PDT/PTT synergistic therapy. Overall, we firstly established an “all active” delivery system integrating the features of nanomedicine with biological functions of macrophages, providing a novel insight for cell-mediated delivery platform and tumor targeted multimodality anti-cancer therapy.

研究领域: 纳米技术 · 癌症治疗 · 免疫学 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

Nanomotors-loaded microneedle patches for the treatment of bacterial biofilm-related infections of wound

Lin Chen,Dan Fang,Junyue Zhang,Xiangyu Xiao,Nan Li,Yue Li,Mimi Wan,Chun Mao

The biofilms formed by bacteria at the wound site can effectively protect the bacteria, which greatly weakens the effect of antibiotics. Herein, a microneedle patch for wound treatment is designed, which can effectively penetrate the biofilms in a physical way because of the penetration ability of the microneedles and the motion behavior of the nanomotors, and deliver bacterial quorum sensing inhibitor luteolin (Le) and nanomotors with multiple antibacterial properties within biofilms. Firstly, the nanomotors-loaded microneedle patches are prepared and characterized. The results of in vitro and in vivo experiments show that the microneedle patches have good biosafety and antibacterial properties. Among them, Le can inhibit the growth of biofilms. Further, under near-infrared (NIR) irradiation, the nanomotors loaded with photosensitizer ICG and nitric oxide (NO) donor L -arginine (L-Arg) can move in the biofilms under the double driving effect of photothermal and NO, and can give full play to the multiple anti-biological infection effects of photothermal therapy (PTT), photodynamic therapy (PDT) and NO, and finally realize the effective removal of biofilms and promote wound healing. The intervention of nanomotor technology has brought about a new therapeutic strategy for bacterial biofilm-related infection of wound.

研究领域: 生物医学工程 · 药学 · 伤口愈合 · 纳米技术 · 传染病
✓ 已验证 产品关联 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2023 · IF 8

Cell Membrane Coated pH-Responsive Intelligent Bionic Delivery Nanoplatform for Active Targeting in Photothermal Therapy

Xiangyu Zhang,Zelai He

Aim To produce pH-responsive bionic high photothermal conversion nanoparticles actively targeting tumors for sensitizing photothermal therapy (PTT).Materials and Methods The bionic nanoparticles (ICG-PEI@HM NPs) were prepared by electrostatic adsorption of indocyanine green (ICG) coupled to polyethyleneimine (PEI) and modified with tumor cell membranes. In vitro and in vivo experiments were conducted to investigate the efficacy of ICG-PEI@HM-mediated PTT.Results The intelligent responsiveness of ICG-PEI@HM to pH promoted the accumulation of ICG and enhanced the PTT performance of ICG-PEI@HM NPs. Compared with free ICG, NPs exhibited great photothermal stability, cellular uptake, and active tumor targeting for PTT.Conclusion ICG-PEI@HM NPs can enhance the efficacy of PTT and can be used as a new strategy for the construction of photothermal agents.

CAS / MDL: 64-17-5 67-68-5
研究领域: 纳米技术 · 生物医学工程 · 癌症研究 · 治疗学
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Advanced Healthcare Materials · 2020 ·Vol. 9 ·期 14 ·2000205 · IF 7.367

Bioactive MOFs Based Theranostic Agent for Highly Effective Combination of Multimodal Imaging and Chemo-Phototherapy

Yuda Zhu,Nini Xin,Zi Qiao,Suping Chen,Lingwan Zeng,Yusheng Zhang,Dan Wei,Jing Sun,Hongsong Fan

Bioactive metal–organic frameworks (bio-MOFs) built from biofunctional metal ions and linkers show a new strategy to construct multifunctional theranostic platforms. Herein, a bio-MOF is synthetized via the self-assembling of Fe 3+ ions and doxorubicin hydrochloride (DOX) molecules. Then, through a stepwise assembly strategy, another bio-MOFs structure consisting of Gd 3+ ions and 1,3,5-benzenetricarboxylic acid (H 3 BTC) is wrapped on the surfaces of Fe-DOX nanoparticles, followed by adsorbing photosensitizer indocyanine green (ICG). Specifically, the Gd-MOF shell structure can not only act as a contrast agent for magnetic resonance imaging (MRI), but also provides protection for Fe-DOX cores, controlling the release of DOX. The photoacoustic and photothermal imaging (PAI and PTI) methods are successfully introduced to the platform by loading ICG, providing potential applications for multimodal biological imaging. The in vitro and in vivo outcomes indicate that the Fe-DOX@Gd-MOF-ICG nanoplatform exhibits outstanding synergistic antitumor performance via MR/PA/PT imaging guided chemotherapy, photothermal and photodynamic combination therapy. The work may encourage further exploration of bio-MOFs based multifunctional theranostic platforms for multimodal imaging guided compound antitumor therapy, which will open an avenue of MOFs toward biological applications.

研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Quintuple Free-Radical Therapy: An Ultralong-Retention FAND for NIR-Involved Multiple Site-Acting Hypoxic Tumor Therapy

Chuang Zhang,Dongxu Zhao,Fang Fang,Lin Zhu,Weiyu Li,Sa Wang,Yueyun Fan,Jiani Yang,Yanhong Liu,Jinfeng Zhang

The heavy dependence on intratumoral O 2 and H 2 O 2 availability has greatly restricted ROS-based therapy. Although O 2 /H 2 O 2 -irrelevant free-radical nanogenerator has garnered tremendous attention as a promising anticancer candidate to overcome the above intrinsic limitations of ROS-based treatment, the practical therapeutic efficacy of free-radical therapy is still hindered by limited free-radical type and inferior tumor retention performance. Herein, inspired by the new concept of full-API nanodrug (FAND) with 100% active pharmaceutical ingredient (API) content and repurposing of clinical anti-malaria drug artesunate (ARTE) as an anticancer free-radical generator, the AFeI FANDs composed of ARTE, human essential Fe 3+ , and FDA-approved fluorescent agent ICG for hypoxic tumor therapy are rationally designed and constructed. Attractively, the completely pharmaceutically active components ARTE, Fe 3+ , and ICG can be responsively liberated in the acidic tumor microenvironment and synergistically produce five types of free radicals including •O 2 − , •C, •OH, LOO•, and 1 O 2 , leading to robust mitochondrial injury, nuclear DNA damage, and lipid peroxides. More importantly, the AFeI FANDs displayed ultralong tumor retention longer than 108 h and favorable tumor suppression outcomes under mild NIR irradiation. Collectively, the presented first paradigm of FAND-based quintuple free-radical therapy expands new horizons for the development of clinically transferable nanomedicine for tumor therapy.

研究领域: 癌症治疗 · 纳米医学 · 药学 · 生物医学工程 · 光化学
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