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Journal of Materials Chemistry B · 2013 ·Vol. 1 ·期 9 ·1326-1332 · IF 0

Fabrication of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)/ALG modified CaCO3 as drug carriers with the function of tumor selective recognition

Wei Cui,Yue Cui,Jie Zhao,Junbai Li

Layer-by-layer assembled TRAIL/ALG shells have been successfully coated on the surface of highly loaded doxorubicin (DOX) calcium carbonate (CaCO3) nanoparticles as drug carriers. The assembled core/shell structure was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). They show that the assembled TRAIL/ALG coated DOX@CaCO3 nanocomposites can be internalized by cancer cells. The outer layer of the system is TRAIL which can be specifically recognized by tumors and leads to the apoptosis of tumors. The release of DOX can directly kill the cancer cells. This demonstrates that the core/shell nanocomposites of TRAIL/ALG-CaCO3 loaded with DOX have good potential applications in the treatment of cancer.

研究领域: 生物医学工程 · 纳米医学 · 肿瘤学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2015 · IF 3.368

Layer by layer assembly of albumin nanoparticles with selective recognition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Wei Cui,Anhe Wang,Jie Zhao,Xiaoke Yang,Peng Cai,Junbai Li

Crosslinked albumin nanoparticles which loaded with doxorubicin (DOX) were fabricated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and biocompatible polysaccharide, alginate (ALG), using layer-by-layer technique. Albumin nanoparticles exhibited narrow size distribution and fluorescent property. The assembled core/shell structure of the nanoparticles can be internalized more easily with the cancer cells, which attributes to TRAIL binding with death receptors. TRAIL still hold bioactive properties after assembled onto the particles. In addition, after loaded into the albumin core nanoparticles, DOX (as the chemotherapeutics) display a synergistic cytotoxic effect on cytotoxicity in combination with TRAIL in vitro . The core/shell nanostructured nanoparticles realized in this study would be used as a promising candidate for novel drug carriers.

研究领域: 药剂学 · 肿瘤学 · 生物医学工程
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2017 · IF 4.233

Hollow mesoporous carbon as a near-infrared absorbing carrier compared with mesoporous carbon nanoparticles for chemo-photothermal therapy

Xian Li,Yue Yan,Yuanzhe Lin,Jian Jiao,Da Wang,Donghua Di,Ying Zhang,Tongying Jiang,Qinfu Zhao,Siling Wang

In this study, hollow mesoporous carbon nanoparticles (HMCN) and mesoporous carbon nanoparticles (MCN) were used as near-infrared region (NIR) nanomaterials and drug nanocarriers were prepared using different methods. A comparison between HMCN and MCN was performed with regard to the NIR-induced photothermal effect and drug loading efficiency. The results of NIR-induced photothermal effect test demonstrated that HMCN-COOH had a better photothermal conversion efficacy than MCN-COOH. Given the prominent photothermal effect of HMCN-COOH in vitro , the chemotherapeutic drug DOX was chosen as a model drug to further evaluate the drug loading efficiencies and NIR-triggered drug release behaviors of the nanocarriers. The drug loading efficiency of DOX/HMCN-COOH was found to be up to 76.9%, which was higher than that of DOX/MCN-COOH. In addition, the use of an 808   nm NIR laser markedly increased the release of DOX from both carbon carriers in pH 5.0 PBS and pH 7.4 PBS. Cellular photothermal tests involving A549 cells demonstrated that HMCN-COOH had a much higher photothermal efficacy than MCN-COOH. Cell viability experiments and flow cytometry were performed to evaluate the therapeutic effect of DOX/HMCN-COOH and the results obtained demonstrated that DOX/HMCN-COOH had a synergistic therapeutic effect in cancer treatment involving a combination of chemotherapy and photothermal therapy.

CAS / MDL: 98-00-0 57-09-0 78-10-4
研究领域: 材料科学 · 纳米技术 · 癌症治疗 · 药物递送系统
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Materials · 2020 ·Vol. 13 ·期 18 ·3950 · IF 3.057

pH-Responsive and Biodegradable ZnO-Capped Mesoporous Silica Composite Nanoparticles for Drug Delivery

Minmin Chen,Jinxia Hu,Cancan Bian,Chenghao Zhu,Chen Chen,Zhijun Guo,Zhimin Zhang,Godfred Amfo Agyekum,Zhuoqi Zhang,Xichuan Cao

As a drug delivery system (DDS), traditional mesoporous silica nanoparticles (MSNs) suffer from bioaccumulation in vivo and premature drug release in systemic circulation due to low degradation rate and lack of protective gatekeeper. Herein, we developed a safe and intelligent DDS with characteristics of pH-responsive biodegradation and controlled drug release based on mesoporous silica composite nanoparticles (MSCNs) capped with ZnO quantum dots (ZnO QDs). Acidic degradable MSCNs were successfully synthesized by doping Ca2+and PO43−into the MSNs’ framework. The in vitro doxorubicin hydrochloride (DOX) release was inhibited at neutral pH 7.4 but triggered significantly at pH 5.0 due to the dissociation of ZnO caps. The internalization behavior and cytotoxicity of 4T1 cells indicated MSCNs-ZnO could efficiently deliver DOX into the cells with significant antitumor activity. Such a DDS with pH-responsive biodegradation and controlled drug release has promising potential for cancer therapy.Keywords:mesoporous silica composite nanoparticles (MSCNs);ZnO QDs;pH-responsive biodegradability;pH-responsive drug delivery

研究领域: 纳米技术 · 药物递送 · 材料科学 · 生物医学工程
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SOLID STATE SCIENCES · 2022 · IF 3.752

Hollow mesoporous structured MnFe2O4 nanospheres: A biocompatible drug delivery system with pH-responsive release for potential application in cancer treatment

Jie Gao,Fangfang Si,Fang Wang,Yakun Li,Guangshuo Wang,Jing Zhao,Yingying Ma,Ruitao Yu,Yanhong Li,Changhai Jin,Dong Li

In this paper, a novel pH-responsive drug delivery system based on hierarchical hollow mesoporous MnFe 2 O 4 nanospheres was developed for potential application in cancer treatment. The well-defined hollow mesoporous MnFe 2 O 4 nanospheres were directly fabricated via a facile one-step solvothermal approach without the involvement of additional templates. A mechanism of inside-out Ostwald ripening was suggested to account for the formation of hollow mesoporous nanostructures . The morphology, crystal structure, chemical composition, magnetic properties , thermal stability and mesoporous characteristics of the fabricated MnFe 2 O 4 nanospheres were comprehensively assessed based on various analysis techniques. The resulting hollow mesoporous MnFe 2 O 4 nanospheres with a high biocompatibility were able to be served as a nanocarrier for loading and delivering of anticancer drug doxorubicin (DOX). In vitro drug release study revealed that DOX release from DOX-loaded MnFe 2 O 4 nanospheres was significantly restrained in pH 7.4 phosphate buffer solution (PBS), while it was markedly accelerated in pH 4.5 PBS. The results of cytotoxicity assay and inverted biological microscopy demonstrated that the DOX-loaded MnFe 2 O 4 nanospheres were more cytotoxic against HepG2 cells than MnFe 2 O 4 nanospheres due to the evident inhibition effect of released DOX from the constructed drug delivery system. Therefore, the developed pH-responsive delivery system will have a great potential for its practical application in cancer treatment.

研究领域: 纳米技术 · 癌症研究 · 材料科学 · 生物医学工程
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CELL PROLIFERATION · 2021 ·Vol. 54 ·期 9 ·e13105 · IF 6.831

Aptamer-mediated synthesis of multifunctional nano-hydroxyapatite for active tumour bioimaging and treatment

Wenqing Zhang,Ronghui Zhou,Yuting Yang,Shuanglin Peng,Dexuan Xiao,Tingting Kong,Xiaoxiao Cai,Bofeng Zhu

Objectives The nano-hydroxyapatite (nHAp) is widely used to develop imaging probes and drug carriers due to its excellent bioactivity and biocompatibility. However, traditional methods usually need cumbersome and stringent conditions such as high temperature and post-modification to prepare the functionalized nHAp, which do not benefit the particles to enter cells due to the increased particle size. Herein, a biomimetic synthesis strategy was explored to achieve the AS1411-targeted tumour dual-model bioimaging using DNA aptamer AS1411 as a template. Then, the imaging properties and the biocompatibility of the synthesized AS-nFAp:Gd/Tb were further investigated. Materials and methods The AS-nFAp:Gd/Tb was prepared under mild conditions through a one-pot procedure with AS1411 as a template. Besides, the anticancer drug DOX was loaded to AS-nFAp:Gd/Tb so as to achieve the establishment of a multifunctional nano-probe that integrated the tumour diagnosis and treatment. The AS-nFAp:Gd/Tb was characterized by transmission electron microscopy (TEM), energy disperse X-ray Spectroscopy (EDS) mapping, X-ray photoelectron spectroscopy (XPS) spectrum, X-ray diffraction (XRD), fourier-transformed infrared (FTIR) spectroscopy, capillary electrophoresis analyses, zeta potential and particle sizes. The in vitro magnetic resonance imaging (MRI) and fluorescence imaging were performed on an MRI system and a confocal laser scanning microscope, respectively. The potential of the prepared multifunctional nHAp for a targeted tumour therapy was investigated by a CCK-8 kit. And the animal experiments were conducted on the basis of the guidelines approved by the Animal Care and Use Committee of Sichuan University, China. Results In the presence of AS1411, the as-prepared AS-nFAp:Gd/Tb presented a needle-like morphology with good monodispersity and improved imaging performance. Furthermore, due to the specific binding between AS1411 and nucleolin up-expressed in cancer cells, the AS-nFAp:Gd/Tb possessed excellent AS1411-targeted fluorescence and MRI imaging properties. Moreover, after loading chemotherapy drug DOX, in vitro and in vivo studies showed that DOX@AS-nFAp:Gd/Tb could effectively deliver DOX to tumour tissues and exert a highly effective tumour inhibition without systemic toxicity compared with pure DOX. Conclusions The results indicated that the prepared multifunctional nHAp synthesized by a novel biomimetic strategy had outstanding capabilities of recognition and treatment for the tumour and had good biocompatibility; hence, it might have a potential clinical application in the future.

CAS / MDL: 19598-90-4 57584-27-7
研究领域: 纳米技术 · 生物医学工程 · 癌症研究 · 材料科学 · 药学
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MOLECULAR PHARMACEUTICS · 2018 · IF 4.556

Hybrid Mesoporous–Microporous Nanocarriers for Overcoming Multidrug Resistance by Sequential Drug Delivery

Liucan Wang,Haidi Guan,Zhenqiang Wang,Yuxin Xing,Jixi Zhang,Kaiyong Cai

Combination chemotherapy with a modulator and a chemotherapeutic drug has become one of the most promising strategies for the treatment of multidrug resistance (MDR) in cancer therapy. However, the development of nanocarriers with a high payload and sequential release of therapeutic agents poses a significant challenge. In this work, we report a type of hybrid nanocarriers prepared by polydopamine (PDA) mediated integration of the mesoporous MSN core and the microporous zeolite imidazolate frameworks-8 (ZIF-8) shell. The nanocarriers exploit storage capacities for drugs based on the high porosity and molecular sieving capabilities of ZIF-8 for sequential drug release. Particularly, large amounts of an anticancer drug (DOX, 607 μg mg–1) and a MDR inhibitor curcumin (CUR, 778 μg mg–1) were sequentially loaded in the mesoporous core via π–π stacking interactions mediated by PDA and in the microporous shell via the encapsulation during ZIF-8 growth. The sustained release of DOX was observed to follow earlier and faster release of CUR by acid-sensitive dissolution of the ZIF-8 shell. Furthermore, the nanoparticles showed good biocompatibility and effective cellular uptake in in vitro evaluations using drug-resistant MCF-7/ADR cancer cells. More importantly, the preferentially released CUR inhibited the drug efflux function of the membrane P-glycoprotein (P-gp), which subsequently facilitated the nuclear transportation of DOX released from the PDA-MSN core, and, in turn, the synergistic effects on killing MDR cancer cells. The hybrid mesoporous–microporous nanocarrier holds great promise for combination chemotherapy applications on the basis of sequential drug release.

研究领域: 癌症治疗 · 纳米技术 · 药学科学 · 药物递送系统
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ACS Applied Bio Materials · 2019 · IF 0

Combating Multidrug Resistance through an NIR-Triggered Cyanine-Containing Amphiphilic Block Copolymer

Jia Tian,Chao Xiao,Baoxuan Huang,Xiaoze Jiang,Hongliang Cao,Feng Liu,Weian Zhang

Nowadays, multidrug resistance is the main challenge during cancer chemotherapy. Photochemical internalization (PCI) has been demonstrated to be a unique and promising approach to overcome multidrug resistance with light-harnessed activation. Here, an amphiphilic pH-responsive block copolymer with IR780 at the junction point [PEG-IR780-PDEAEMA; PEG, poly(ethylene glycol); PDEAEMA, poly((diethylamino)ethyl methacrylate)] has been designed as a perfect drug release platform as well as a functional macromolecular photosensitizer of PCI. PEG-IR780-PDEAEMA was synthesized by the combination of RAFT polymerization and click chemistry and further self-assembled into spherical micelles in aqueous solution. Notably, IR780 moieties were dispersed regularly around the core of the spherical micelles, which led to the diminishment of the aggregation-caused quenching effect of photosensitizers and high singlet oxygen quantum yield. Confocal laser scanning microscopy results showed that a high amount of doxorubicin (DOX) was translocated into the nucleus with NIR light irradiation through the PCI effect. Moreover, DOX-loaded PEG-IR780-PDEAEMA micelles showed much higher phototoxicity under short-time NIR light irradiation than their dark toxicity. Therefore, this DOX-loaded drug release platform based on pH-sensitive IR780-containing block copolymers has the potential to offer an efficient strategy for addressing drug resistance.

研究领域: 癌症研究 · 聚合物化学 · 药物科学 · 生物医学工程
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RSC Advances · 2017 ·Vol. 7 ·期 41 ·25694-25701 · IF 3.108

Amphiphilic copolymer and TPGS mixed magnetic hybrid micelles for stepwise targeted co-delivery of DOX/TPP–DOX and image-guided chemotherapy with enhanced antitumor activity in liver cancer

Xiaoju Shi,Guoyue Lv,Xiaodong Sun,Dianbo Cao,Guangyi Wang,Yulei Chang

Recently, several targeted drug delivery systems have shown promising antitumor activity towards different types of cancer. However, targeting the tumor microenvironment, cellular surface and/or only one organelle may not achieve the expected therapeutic effects. Herein, a targeted drug delivery with stepwise targeting and image-guided strategy was obtained for enhancing antitumor therapy and overcoming various problems caused by the random drug distribution of traditional medicine. In this design, a multifunctional nanoplatform, TPGS/PPG2L@IONPs@DOX/TPP–DOX, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(amidoamine)-lactose acid (mPEG-PCL-G2.0 PAMAM-LA, PPG2L) copolymer and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), as a co-carrier, incorporates iron oxide nanoparticles (IONPs) as imaging agents and loads a DOX/triphenylphosphonium (TPP)–DOX drug for chemotherapy. In this nanoplatform micelle, the LA as targeting moieties to hepatocarcinoma cells is the first targeting step. After the drug is released from the hybrid micelles, the incorporated DOX and TPP–DOX target delivery to nuclei and mitochondria for the next targeting step. Furthermore, with the help of MRI contrast agents of IONPs, the distribution of hybrid micelles was monitored. As a result, the hybrid micelles demonstrated enhanced antitumor cell activity in both HepG2 and HepG2/DOX cells. The results indicated that the multifunctional hybrid micelles showed great potential in enhancing antitumor activity under image-guided and stepwise targeted chemotherapy.

CAS / MDL: 9002-96-4
研究领域: 药学 · 癌症研究 · 纳米技术 · 医学影像
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Bioengineering & Translational Medicine · 2024 · IF 6.1

Two-pronged reversal of chemotherapy resistance by gold nanorods induced mild photothermal effect

Qi Shang,Ziyan Chen,Jing Li,Mingmei Guo,Jiapei Yang,Zhu Jin,Yuanyuan Shen,Shengrong Guo,Feihu Wang

Chemotherapy treatment outcomes are severely restricted by multidrug resistance (MDR), in which tumors develop a multiple cross-resistance toward drug involving the pump and nonpump resistance mechanisms, resulting in drug efflux and defending against drug toxicity. Herein, we constructed a pH and near infrared (NIR) light responsive nanomedicine DOX@FG based on gold nanorods (GNRs) that demonstrated the potential to improve chemotherapy outcomes by overcoming MDR. DOX@FG was constructed by conjugating folic acid (FA) and doxorubicin (DOX) derivatives onto GNRs, where the DOX derivatives possessed an acid-labile hydrazone bond. Stimulated by the acidic media in endocytic organelles, DOX@FG exhibited a responsive dissociation for the controlled release of chemotherapeutic DOX. Surprisingly, we found the mild photothermal effect elicited by GNRs under NIR irradiation simultaneously inhibited the pump and nonpump resistance mechanisms, enhancing the intracellular DOX accumulation and sensitizing the cancer cells to DOX, collectively amplify the chemotherapy efficacy and delay the MCF-7/ADR breast tumor growth. This intelligent DOX@FG nanomedicine with the potential for two-pronged reversal of MDR may provide a prospective way to encourage chemotherapy efficacy.

研究领域: 纳米医学 · 癌症治疗 · 光热疗法 · 药物递送系统 · 生物医学工程
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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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BIOMATERIALS · 2020 · IF 10.317

ROS-augmented and tumor-microenvironment responsive biodegradable nanoplatform for enhancing chemo-sonodynamic therapy

Jie An,Yong-Guo Hu,Kai Cheng,Cheng Li,Xiao-Lin Hou,Gang-Lin Wang,Xiao-Shuai Zhang,Bo Liu,Yuan-Di Zhao,Ming-Zhen Zhang

Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor.

研究领域: 纳米技术 · 癌症治疗 · 药物递送系统 · 生物医学工程
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