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REACTIVE & FUNCTIONAL POLYMERS · 2020 · IF 3.333

Smart drug carrier based on polyurethane material for enhanced and controlled DOX release triggered by redox stimulus

Chao Yu,Xing Tan,Zhenzhu Xu,Guodian Zhu,Wenqi Teng,Qingzhen Zhao,Zhong Liang,Zhimin Wu,Di Xiong

A series of amphiphilic polymer mPEG-PUSS-mPEG were developed by a combination of ring opening polymerization (ROP) and polyaddition reaction and its self-assembled micelles were developed for hydrophobic anticancer drugs delivery. Polymeric critical micellar concentration (CMC) values in aqueous solution were about 2.8–5.5 mg/L. And the partition equilibrium constant ( K v ) of pyrene in micellar solutions ranged from 1.52 × 10 5 to 2.20 × 10 5 . The average sizes of the self-assembled blank and DOX-loaded micelles were 160–180 nm determined by dynamic light scattering (DLS). The morphology of the DOX-loaded micelles was spherical by transmission electron microscopy (TEM) and scanning electron microscopy (SEM).The in vitro drug release behaviors of DOX and PTX from mPEG-PUSS-mPEG micelles were investigated at different simulated conditions. We found that the PTX release was significantly accelerated by redox stimuli compared with DOX-loaded reduction-sensitive PU micelles. The change of the size of this system under different conditions was further evaluated by DLS. DOX-loaded mPEG-PUSS-mPEG micelles in 50% fetal bovine serum (FBS) were evaluated the hemocompatibility. In addition, the self-assembly process of polymers mPEG-PUSS-mPEG in aqueous solution for micellar formation was also investigated by means of dissipative particle dynamics (DPD) simulations.AndCCK-8 assays revealed that the mPEG-PUSS-mPEG materials had low toxicity, but the DOX-loaded micelles showed a high cytotoxicity against HepG2 tumor cells. All results demonstrate that mPEG-PUSS-mPEG self-assembled micelles are a very promising for hydrophobic anticancer drugs delivery.

研究领域: 材料科学 · 药剂学 · 生物医学工程 · 癌症研究
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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

A dual-targeting Fe3O4@C/ZnO-DOX-FA nanoplatform with pH-responsive drug release and synergetic chemo-photothermal antitumor in vitro and in vivo

Xuan Liu,Chen Wang,Xueyan Wang,Chen Tian,Yuhua Shen,Manzhou Zhu

Designing a proper intelligent platform to target cancer cells accurately and reducing its toxic side effects on normal tissues remain a challenge in medicine application. Herein, a novel dual-targeted and tumor microenvironment-triggered Fe 3 O 4 @carbon(C)/ZnO-doxorubicin (DOX) -folic acid (FA) drug delivery system with porous structure was designed and fabricated for the first time. The co-presence of Fe 3 O 4 core and FA molecules functioned successfully could successfully realize the magnetic targeting and cancer cell-specific targeting. In addition, pH-responsive ZnO and porous carbon both derived directly from zinc-2-methylimidazolate complex (Zn-ZIF) could play the roles of “gatekeeper” and photothermal agent, respectively. The former could efficiently block the drug within mesoporous in blood environment for decreasing the damage to the normal tissues and achieving the controlled DOX release in the simulated and real acidic tumor microenvironment. And the latter could exhibit the intrinsic photothermal conversion efficiency upon 638 nm laser irradiation. Therefore, the Fe 3 O 4 @C/ZnO-DOX-FA nanoplatform integrated dual targeting, controlled chemotherapy with photothermal therapy (PTT) for cancer, displaying a significantly superior synergistic anticancer efficiency both in vitro and in vivo experiments to either monotherapy. Above results suggested the prepared nanoplatforms might be a promising candidate for effectively synergetic therapeutics to cancers.

研究领域: 生物医学工程 · 纳米医学 · 肿瘤学
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Nanoscale · 2019 ·Vol. 11 ·期 45 ·21759-21766 · IF 6.97

One-pot synthesis of hollow PDA@DOX nanoparticles for ultrasound imaging and chemo-thermal therapy in breast cancer

Tao Zhang,Zhenqi Jiang,Ting Xve,Shan Sun,Juan Li,Wenzhi Ren,Aiguo Wu,Pintong Huang

Constructing nanocarriers with high drug loading capacity is a challenge, which limits the effective delivery of drugs to solid tumors. Here, we reported a one-pot synthesis of hollow nanoparticles (NPs) encapsulated by doxorubicin (DOX) and modified with polydopamine (PDA) to form PDA@DOX NPs for breast cancer treatment. PDA@DOX NPs demonstrated exceptionally high capacity (53.16%) for loading DOX. In addition, when PDA@DOX NPs were administered systemically, they exhibited responsive aggregation in the tumor sites and demonstrated a good controlled release effect for DOX due to the weak acidic environment of the tumor sites and targeting near-infrared (NIR) light irradiation. The PDA outer layer absorbed the near-infrared (NIR) light and facilitated simultaneous generation of heat energy for destroying the tumor cells to release the drug upon NIR irradiation. Moreover, this NIR-activated combined/synergistic therapy exhibited remarkably complete tumor growth suppression in a breast cancer mouse model. Importantly, NPs exhibited a good ultrasound performance both in vitro and in vivo, which could monitor the treatment process. In conclusion, this NIR-activated PDA@DOX NP system is demonstrated as a good US-guided combination (chemotherapy + PTT) therapy platform with high loading capacity and controlled drug release characteristics, which is promising for the treatment of breast cancer.

CAS / MDL: 23491-45-4 62-31-7
研究领域: 癌症治疗 · 纳米医学 · 生物医学工程 · 药学科学 · 医学影像
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Biodegradable Imprinted Polymer Based on ZIF-8/DOX-HA for Synergistically Targeting Prostate Cancer Cells and Controlled Drug Release with Multiple Responses

Yuzhuo Song,Shuang Han,Shiwei Liu,Ruonan Sun,Le Zhao,Chen Yan

Improving the drug loading and delivery efficiency of biodegradable nanomaterials used for targeting prostate cancer (PCa) remains a challenging task. To accomplish this task, herein, a new surface molecularly imprinted polymer (ZIF-8/DOX-HA@MIP) was designed and constructed with a hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework loaded with doxorubicin (DOX) as a substrate and a responsive molecularly imprinted polymer film as a shell. Owing to the large surface area of ZIF-8, DOX was successfully loaded into the ZIF-8/DOX-HA@MIP with a high drug loading efficiency (more than 88%). In vitro cell experiments have shown that the strengthened targeting ability of ZIF-8/DOX-HA@MIP to PCa cells was realized through the synergistic effect of HA and the molecularly imprinted membrane. Under the condition of simulated tumor microenvironment solution, Zn species were released and the particle size of ZIF-8/DOX-HA@MIP decreased gradually by the synergistic effect of hyaluronidase, pH, and glutathione, showing excellent biodegradability. In vivo antitumor research indicated the excellent antitumor activity and biocompatibility of ZIF-8/DOX-HA@MIP. The multifunctional ZIF-8/DOX-HA@MIP constructed herein provides a novel impetus for the development of targeted drug delivery in PCa treatment and a new strategy for treating other tumors.

研究领域: 纳米技术 · 药学 · 癌症研究 · 材料科学
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Cancer Nanotechnology · 2022 ·Vol. 13 ·期 1 ·1-13 · IF 7.917

Facile synthesis of degradable DOX/ICG co-loaded metal–organic frameworks for targeted drug release and thermoablation

Liu Bei,Liu Xiaoning,Zhang Xiangyu,Wu Xi,Li Chuanbo,Sun Zhaogang,Chu Hongqian

Background Despite the increasing interest in combination therapy for the treatment of cancer, controlled delivery of different therapeutics with high body-clearance efficacy and cancer cell specificity remained a great challenge. In this study, a novel codelivery system was synthesized through one-pot coordination-driven self-assembly of 2-methylimidazole, zinc ion and chemotherapeutic drug (doxorubicin, DOX), followed by a surface decoration of photothermal agent (indocyanine green, ICG). To improve the targeting specificity performance, folic acid-conjugated polyethylene glycol (FA-PEG) antennas was connected on the surface of nanoparticles.Results The hybrid nanoparticles keep stable under neutral physiological condition but decompose when exposed to acidic environment, resulting in the on-demand release of DOX and ICG for chemo-photothermal combined therapy. Moreover, by switching the initial large size (~ 94 nm) to an ultrasmall size (∼10 nm) in cancer cells, the nanoparticles hold great potential to avoid nanotoxicity for clinical applications.Conclusion sThis work provides a new strategy for co-delivery of different therapeutics for combined cancer therapy with high cancer cell specificity and low nanotoxicity.

CAS / MDL: 3599-32-4 67-56-1
研究领域: 癌症治疗 · 纳米技术 · 药物递送系统 · 材料科学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

A Multifunctional PB@mSiO2–PEG/DOX Nanoplatform for Combined Photothermal–Chemotherapy of Tumor

Yun Yan Su,Zhaogang Teng,Hui Yao,Shou Ju Wang,Ying Tian,Yun Lei Zhang,Wen Fei Liu,Wei Tian,Li Juan Zheng,Nan Lu,Qian Qian Ni,Xiao Dan Su,Yu Xia Tang,Jing Sun,Ying Liu,Jiang Wu,Gui Fen Yang,Guang Ming Lu,Long Jiang Zhang

In this work, we design mesoporous silica-coated Prussian blue nanocubes with PEGyltation to construct multifunctional PB@mSiO2–PEG nanocubes. The PB@mSiO2–PEG nanocubes have good biocompatibility, excellent photothermal transformation capacity, in vivo magnetic resonance and photoacoustic imaging ability. After loading antitumor drug doxorubicin (DOX) in the PB@mSiO2–PEG nanocubes, the constructured PB@mSiO2–PEG/DOX nanoplatforms show an excellent pH-responsive drug release character within 48 h, namely, an ultralow cumulative drug release amount of 3.1% at pH 7.4 and a high release amount of 46.6% at pH 5.0. Upon near-infrared laser irradiation, the PB@mSiO2–PEG/DOX nanoplatforms show an enhanced synergistic photothermal and chemical therapeutic efficacy for breast cancer than solo photothermal therapy or chemotherapy.

研究领域: 纳米技术 · 生物医学工程 · 癌症研究 · 药物递送系统 · 材料科学
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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Novel Protease-Free Long-Lasting Chemiluminescence System Based on the Dox-ABEI Chimeric Magnetic DNA Hydrogel for Ultrasensitive Immunoassay

Haiping Wu,Min Zhao,Jia Li,Xiaoyan Zhou,Tiantian Yang,Dezhang Zhao,Ping Liu,Huangxian Ju,Wei Cheng,Shijia Ding

Most of chemiluminescence (CL) substrates exhibit the flash-type light emission. Therefore, the long-lasting CL system is always the crown in the field of CL-based analysis methodology. In this work, we constructed a Dox-ABEI chimeric magnetic DNA hydrogel (MDH) as a novel protease-free long-lasting CL reaction system. The functional MDH can transform flash-type ABEI/H2O2/CO2+ reaction into a glow-type CL system because of its block effect on delaying the diffusion rate of co-reactants, making the CL reaction gradually occur. More importantly, the functional MDH possessed the advantages of biocompatibility and controllability and could be well-designed to incorporate different biosensing strategies. Subsequently, we established a functional MDH-based long-lasting CL immunoassay system for ultrasensitive and highly specific detection of d-dimer and fibrin degradation products (FDPs). The designed CL immunoassay can detect d-dimer and FDP down to 53.7 and 31.6 fg/mL, respectively, with a wide line ranging from 100 fg/mL to 100 ng/mL, which was superior to the previously reported CL biosensing strategies. Moreover, benefiting from the magnetic separation of MDH and excellent CL performance, the developed immunoassaying method was successfully applied in the detection of clinical samples, which showed a close correlation with clinical reference technology. Thus, this functional MDH proved to be an excellent long-lasting CL system and a potential technical platform for clinical bioanalysis applications.

研究领域: 分析化学 · 生物化学 · 生物技术 · 临床化学
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ChemNanoMat · 2023 ·Vol. 9 ·期 4 ·e202200532 · IF 3.8

NIR-triggered Synergetic Photothermal and Chemotherapy Cancer Treatment Based on SiO2@Au@SiO2@QDs-DOX Composite Structural Particles

Xinbing Jiang,Lu Qiao,Huan Yang,Ben Q Li,Shujiang Ding

Graphical SiO 2 @Au@SiO 2 @QDs nanocomposite with dual-functionality of simultaneous heating and temperature sensing were prepared. The heating is activated by a NIR laser through SPR effect while thermal sensing is accomplished by QDs PL thermometry. These nanocomposites are used as a drug carrier for in vitro chemotherapy-photothermal co-treatment for malignant cells. This paper reports the synthesis of multi-layer SiO 2 @Au@SiO 2 @QDs nanoparticles with a dual-functionality of simultaneous heating and temperature sensing and their applications to in vitro chemo-thermal therapy. The heating is activated by a NIR-light through resonance excitation of surface plasma while in-situ thermal sensing is accomplished by the QDs photoluminescent (PL) effect. These dual function nanoparticles are used as a drug carrier for in vitro chemotherapy-photothermal co-treatment for malignant cells. A comparative study of drug release profiles was performed with and without 808 nm laser irradiation. The drug release rate was accelerated by a rise of temperature, which is induced by plasmonic heat generation associated with Au nanoshells; while the temperature change is monitored by the QD nanoparticles at the same time. The results showed that SiO 2 @Au@SiO 2 @QDs-DOX platform enabled the combination of local specific chemotherapy with external near-infrared (NIR) photothermal therapy and significantly improved the efficacy of cancer treatment. This combined treatment demonstrated synergistic chemotherapeutic-thermal effects compared to chemotherapy or photothermal therapy alone, resulting in higher efficacy.

CAS / MDL: 78-10-4
研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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ACS Biomaterials Science & Engineering · 2018 · IF 4.432

DOX/ICG Coencapsulated Liposome-Coated Thermosensitive Nanogels for NIR-Triggered Simultaneous Drug Release and Photothermal Effect

Lixia Yu,Anjie Dong,Ruiwei Guo,Muyang Yang,Liandong Deng,Jianhua Zhang

Chemo-photothermal therapy has shown enormous potential in treating cancer. To achieve the chemo-photothermal synergistic effect, an efficient nanoparticulate system with the ability for simultaneous codelivery of chemotherapeutic drug and photothermal agent as well as photothermal-triggered drug release is highly desirable. Herein, an in situ polymerization within liposome template was designed to prepare liposome-coated poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-co-AAM)) nanogels, which can efficiently coencapsulate a NIR dye indocyanine green (ICG) and high amount of doxorubicin hydrochloride (DOX). The DOX/ICG coloaded hybrid nanogels, denoted as DI-NGs@lipo, integrated the desirable functions of PEGylated liposomes and thermosensitive nanogels. The PEGylated liposome shell provided excellent storage stability, hemodynamic stability, and fluorescence stability. Meanwhile, the thermosensitive P(NIPAM-co-AAM) nanogels core endowed DI-NGs@lipo with volume phase transition temperature (VPTT) at about 40 °C, allowing for thermo-controlled transformation and drug release. The significant photothermal effect of DI-NGs@lipo and the simultaneous hyperthermia-triggered DOX release were observed under NIR light irradiation. The DI-NGs@lipo was demonstrated to be uptaken by 4T1 murine breast cancer cells via endocytosis, enhancing the distribution of DOX in the cell nucleus. Compared with chemo or photothermal treatment alone, the combination treatment of DI-NGs@lipo with NIR light irradiation induced significantly higher cytotoxicity to 4T1 cells, demonstrating the chemo-photothermal synergistic therapeutic effects on tumor cells. In a word, the strategy provided here offers a facile approach to develop a multifunctional nanoplatform for codelivery of DOX and ICG, which can synergistically improve the cancer-cell-killing efficiency, demonstrating great potential in chemo-photothermal therapy.

CAS / MDL: 97281-47-5
研究领域: 纳米技术 · 癌症治疗 · 药物递送系统 · 光热疗法
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Acta Biomaterialia · 2024 · IF 9.4

A Nanomedicine Composed of Polymer-ss-DOX and Polymer-Ce6 Prodrugs with Monoclonal Antibody Targeting Effect for Anti-tumor Chemo-Photodynamic Synergetic Therapy

Liang Yu,Mingzu Zhang,Jinlin He,Xingwei Sun,Peihong Ni

ABSTRACT Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity and uncontrolled drug release due to their lack of targeting. To improve the bioavailability of drugs and reduce side effects, we have developed a mixed micelle of nanomedicine composed of two prodrugs with surface modified monoclonal antibody for cancer therapy. In this system, Nimotuzumab was used as targeting ligands of the mixed micelles (named as DCMMs) that is composed of polymer-doxorubicin prodrug (abbreviated as PEG- b -P(GMA- ss -DOX)) and maleimide polyethylene glycol-chlorin e6 (abbreviated as Mal-PEG-Ce6). The mixed micelles modified with Nimotuzumab (named as NTZ-DCMMs) bind to overexpressed EGFR receptors on Hepatoma-22 (H22) cells. Disulfide bonds in PEG- b -P(GMA- ss -DOX) are disrupted in tumor microenvironment, inducing the reduction-responsive release of DOX and leading to tumor cell apoptosis. Simultaneously, Chlorin e6 (Ce6) produced plenty of singlet oxygen ( 1 O 2 ) under laser irradiation to kill tumor cells. In vivo biological distribution and antineoplastic effect experiments demonstrate that NTZ-DCMMs enhanced drug enrichment at tumor sites through targeting function of antibody, dramatically suppressing tumor growth and mitigating cardiotoxicity of drugs. All results prove that NTZ-DCMMs have the ability to actively target H22 cells and quickly respond to tumor microenvironment, which is expected to become an intelligent and multifunctional drug delivery carrier for efficient chemotherapy and photodynamic therapy of hepatoma. Statement of significance Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity due to their lack of targeting. Therefore, it's necessary to develop effective, targeted, and collaborative treatment strategies. We construct a mixed micelle of nanomedicine based on two polymer prodrugs and modified with monoclonal antibody on surface for cancer therapy. Under the tumor cell microenvironment, the disulfide bonds of polymer- ss -DOX were broken, effectively triggering DOX release. The photosensitizer Ce6 could generate a large amount of ROS under light, which synergistically promotes tumor cell apoptosis. By coupling antibodies to the hydrophilic segments of polymer micelles, drugs can be specifically delivered. Compared with monotherapy, the combination of chemotherapy and photodynamic therapy can significantly enhance the therapeutic effect of liver cancer.

CAS / MDL: 5471-63-6
研究领域: 药学 · 纳米技术 · 癌症研究 · 生物医学工程
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JOURNAL OF POROUS MATERIALS · 2024 · IF 2.5

Near-infrared light-mediated HMTNs@PMO-DOX/ICG@HA drug composite nanoparticles enable a synergistic combination of chemical and photothermal therapy for tumors

Cai Xiaoqin,Wu Nian,Song Fangxiang,Luo Honghuan,Li Tingxian,Yan Yibing,Li Songye,Li Yan

Combination therapy for cancers can fully utilize each treatment method’s benefits in order to maximize anti-tumor actions and hence produce superior therapeutic outcomes. In this study, HMTNs@PMO@HA composite nanoparticles, a pH/NIR dual-responsive chemo-photothermal platform, were constructed. The hollow mesoporous titanium dioxide nanoparticles (HMTNs) were prepared by silica-protected calcination and alkali etching, and the periodic mesoporous organosilica (PMO) was coated on top of them to improve the biocompatibility, and then modified by hyaluronic acid (HA) to improve the targeting and cellular uptake of the nanoparticles. This chemo-photothermal platform combined the chemotherapeutic drug doxorubicin (DOX) with the photothermal agent indocyanine green (ICG) to investigate their inhibitory effects on breast cancer cells (MCF-7). Drug loading and release experiments revealed that the platform had a high loading rate of doxorubicin and indocyanine green (DOX: 40.21%; ICG: 25.78%), and the cumulative release rate of the drugs increased in an acidic environment. The results of the photothermal effect evaluation in vitro indicated that the nano-platform had a good photothermal effect. Cytotoxicity and apoptosis assays showed that the nanoparticles combined with NIR had a good inhibitory effect on breast cancer cells (cell viability: 27.68%; apoptosis rate: 43.4%). The above results indicated that the combination therapy used by this nano platform provided high therapeutic efficiency for treating tumors and offered a feasible strategy for combining tumor-targeting with chemo-photothermal therapy.

研究领域: 纳米技术 · 癌症治疗 · 药学 · 生物医学工程
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2020 · IF 3.99

DOX-conjugated CQD-based nanosponges for tumor intracellular pH-triggered DOX release and imaging

Guoping Li,Mingliang Pei,Peng Liu

Novel tumor nanotheranostics were designed by conjugating doxorubicin (DOX) onto the hydrazine-functionalized crosslinked carbon quantum dots (CQDs)/polyethylene glycol bisacrylate (PEGBA) (C-CQD PEGBA -Hy) nanosponges via an acid-labile imine bond for the tumor intracellular real-time imaging and pH-triggered DOX release. The proposed prodrug nanotheranostics with a DOX content of 14.57 % and a mean hydrodynamic diameter around 116 nm showed excellent pH-triggered drug release performance, with a cumulative release of 52.71 % in the simulated tumor intracellular microenvironment in 4 days, while a premature drug leakage of 7.09 % in the simulated normal physiological medium. Besides, the fluorescence could be recovered during the drug release, indicating the potential application for tumor intracellular real-time imaging.

CAS / MDL: 814-68-6
研究领域: 药学 · 生物医学工程 · 肿瘤学
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