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MICROCHIMICA ACTA · 2022 ·Vol. 189 ·期 10 ·1-13 · IF 6.408

Fabrication of a smart drug delivery system based on hollow Ag2S@mSiO2 nanoparticles for fluorescence-guided synergistic photothermal chemotherapy

Gao Minjie,Han Zehua,Wang Zhihua,Zou Xueyan,Peng Lichao,Zhao Yanbao,Sun Lei

A novel near-infrared (NIR) light-triggered smart nanoplatform has been developed for cancer targeting and imaging-guided combined photothermal-chemo treatment. Notably, Ag 2 S has a dual function of photothermal therapy and fluorescence imaging, which greatly simplifies the structure of the system. It can emit fluorescence at 820 nm under an excitation wavelength of 560 nm. The phase-change molecule of 1-tetradecanol (TD) is introduced as a temperature-sensitive gatekeeper to provide the nanocarrier with controlled release capability of doxorubicin (DOX). The nanocarrier (HAg 2 S@mSiO 2 -TD/DOX) shows a high drug loading capacity of 26.3% and exhibits an apparent NIR-responsive DOX release property. Under NIR irradiation, the photothermal effect of HAg 2 S nanocores facilitated the release of DOX through the melting of TD. The cytotoxicity test shows that the nanocarriers have good biocompatibility. As the same time, the synergistic combination leads to a better cancer inhibition effect than individual therapy alone in vitro. Cell uptake tests indicate that the carriers have excellent fluorescence imaging ability and high cellular uptake for HepG2 cells. This work provides a new strategy for the fabrication of smart nanocarriers with simple structures for fluorescence-mediated combination cancer therapy. Graphical abstract Fabrication of a smart drug delivery system based on hollow Ag 2 S@mSiO 2 nanoparticles for fluorescence-guided synergistic photothermal chemotherapy

研究领域: 纳米技术 · 癌症治疗 · 药物递送系统 · 光热疗法 · 荧光成像 · 生物医学工程
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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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DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY · 2019 · IF 2.367

Doxorubicin derivative loaded acetal-PEG-PCCL micelles for overcoming multidrug resistance in MCF-7/ADR cells

Xin-Cheng Zhong,Wen-Hong Xu,Zi-Ting Wang,Wang-Wei Guo,Jie-Jian Chen,Ning-Ning Guo,Tian-Tian Wang,Meng-Ting Lin,Zhen-Tao Zhang,Yi-Ying Lu,Qi-Yao Yang,Min Han,Dong-Hang Xu,Jian-Qing Gao

Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor.Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR.Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo.Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs.Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.

CAS / MDL: 68-12-2 7761-88-8
研究领域: 药学 · 肿瘤学 · 纳米技术 · 药物递送系统
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MICROPOROUS AND MESOPOROUS MATERIALS · 2022 · IF 5.876

A dual drug delivery platform based on thermo-responsive polymeric micelle capped mesoporous silica nanoparticles for cancer therapy

Hongyu Long,Weijun Tian,Shuting Jiang,Jianqing Zhao,Jianren Zhou,Qian He,Zhaomin Tang,Wenzhu Shen,Jiajia Wang

The combination of organic polymers and inorganic nanoparticles to design intelligent nanocarriers is of great significance for effective delivery of anticancer drugs to tumor cells for therapy. Herein, we have prepared a thermo-responsive micelle as a “gatekeeper” to attach on the surface of mesoporous silica nanoparticle (MSN) through disulfide bonds. DOX was encapsulated in both nanocarriers, resulting in a pH/redox/temperature responsive dual drug delivery platform ( [email protected] 2 [email protected] , abbreviated as DMSFPD) with high loading capacity and excellent stimuli-responsive performance for cancer therapy. The cumulative release curve in vitro indicated that DOX could be controllably released from DMSFPD. With the elevated temperature at 40 °C, the uncapping ofF127-PCL250 (FP250) micelle from MSN after GSH stimulus and the shrinkage of FP250 micelle caused a fast release of DOX from both MSN and micelle, which greatly increased the drug concentration immediately. The intracellular uptake and cytocompatibility demonstrated that MSN-S 2 -F127-PCL250 (MSFP250) could be efficiently endocytosed and have shown favorable biocompatibility in both normal and tumoral cells. Cytotoxicity results illustrated that DMSFPD could significantly kill different kinds of cancer cells. Therefore, this dual drug delivery capping platform provides a new and promising strategy for cancer therapy.

研究领域: 药学 · 纳米技术 · 癌症研究
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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 27 ·5464-5472 · IF 4.543

Photothermal gold nanocages filled with temperature sensitive tetradecanol and encapsulated with glutathione responsive polycurcumin for controlled DOX delivery to maximize anti-MDR tumor effects

Zhipeng Zhang,Yun Wang,Shaohui Xu,Yanna Yu,Abid Hussain,Yuanyuan Shen,Shengrong Guo

The design of an ideal drug delivery system with targeted recognition and minimized premature release, especially controlled and specific release that is triggered by endogenous and exogenous dual-stimuli, is a great challenge. A biotin receptor-targeted, near-infrared (NIR) irradiation and redox responsive nano-system has now been developed. The nano-system was constructed by filling the interior of Au nanocages with doxorubicin as a chemotherapy agent trapped in tetradecanol, followed by surface conjugation of biotinylated poly(ethylene glycol)–poly(curcumin-dithiodipropionic acid) (Biotin–PEG–PCDA) as a macromolecular chemosensitizer. Once the nano-system had been delivered into MCF-7/ADR cells by biotin receptor mediated recognition and endocytosis, drug release was triggered by degradation of PCDA via a glutathione induced redox reaction in combination with a solid–liquid change of tetradecanol by photothermal effects under NIR irradiation, which could minimize premature drug release and then maximize the therapeutic efficacy.

研究领域: 癌症治疗 · 药物递送 · 纳米技术 · 材料科学 · 生物医学工程
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2014 · IF 3.005

Sustained release of PTX-incorporated nanoparticles synergized by burst release of DOX⋅HCl from thermosensitive modified PEG/PCL hydrogel to improve anti-tumor efficiency

Shuxin Xu,Weiwei Wang,Xijing Li,Jianping Liu,Anjie Dong,Liandong Deng

As drug therapies become increasingly sophisticated, the synergistic benefits of two or more drugs are often required. In this study, we aimed at improving anti-tumor efficiency of paclitaxel (PTX)-incorporated thermo-sensitive injectable hydrogel by the synergy of burst release of doxorubicin hydrochloride (DOX⋅HCl). Thermosensitive injectable hydrogel composed of nanoparticles assembled from amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) was fabricated. Hydrophobic PTX and hydrophilic DOX⋅HCl were loaded simultaneously in the thermo-sensitive injectable hydrogel by a two-stage entrapment. Thermosensitive gelling behaviors of drug-loading PECT nanoparticle aqueous dispersions were studied. In vitro release profiles of PTX and DOX⋅HCl and in vivo anti-tumor effect by dual drugs from PECT hydrogel were investigated. The results showed that hydrophilic and hydrophobic drugs could be successfully entrapped in PECT hydrogel simultaneously without affecting its thermo-sensitive behavior. In vitro release profiles demonstrated the burst release of DOX⋅HCl and the sustained release of PTX. Anti-tumor effect was improved by a fast and tense attack caused by the burst release of hydrophilic DOX⋅HCl from hydrogel, which was continued by the sequent sustained release of PTX-incorporated nanoparticles and remnant DOX⋅HCl. Unintentionally, entrapped in PECT hydrogel, hydrophilic DOX⋅HCl was observed to have a sustained releasing pattern in vitro and in vivo .

CAS / MDL: 25322-68-3
研究领域: 药学 · 肿瘤学 · 材料科学
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Journal of Materials Chemistry B · 2018 ·Vol. 7 ·期 6 ·974-985 · IF 4.776

NIR-triggered release of DOX from sophorolipid-coated mesoporous carbon nanoparticles with the phase-change material 1-tetradecanol to treat MCF-7/ADR cells

Abid Hussain,Shengrong Guo

To prevent premature drug release from nanoparticles, it is vital to design and prepare controlled and site-specific drug release systems. We investigated a new controllable drug release mesoporous carbon nanoparticle (MCN)-based nano-system with the advantages of enhanced permeability and retention effect (EPR) to target tumors followed by the NIR-induced heat-triggered release of a chemotherapeutic drug to show anti-tumor effects. The pores of MCN with photo-thermal effects were filled with the chemotherapeutic agent doxorubicin (DOX) and the phase change material (PCM) 1-tetradecanol was used as a gatekeeper to trap DOX inside the pores of the mesoporous carbon nanoparticles and the release of DOX inside tumor cells was triggered using NIR irradiation. The surface of MCN was coated with natural sophorolipid (SLPD) to obtain nanoparticles (DOX-PCM@MCN-SLPD) with good biocompatibility, dispersibility and stability in aqueous solutions. The MCN-based nano-system had the ability to load 24% DOX trapped with the PCM before coating with SLPD. It was observed that the release of DOX was temperature-dependent above the melting point of PCM. Once DOXPCM@MCN-SLPD was delivered into MCF-7/ADR cells, the release of DOX was triggered by MCN-borne photo-thermal effects under NIR irradiation. The amount of DOX inside the tumor was visualized via confocal laser scanning microscopy, which showed a higher amount of DOX at a higher temperature compared to that at normal body temperature, further confirming the minimization of premature drug release at 37 °C.

CAS / MDL: 108-95-2
研究领域: 药剂学 · 肿瘤学 · 纳米医学
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Cancer Nanotechnology · 2024 ·Vol. 15 ·期 1 ·1-15 · IF 4.5

Enhanced chemotherapy response in hepatocellular carcinoma: synergistic effects of miR-122 and doxorubicin co-delivery system inducing apoptosis and DNA damage

Lin Xiuyun,Liu Jie,Wu Guangfeng,Yang Xiu,Yan Wenqiang,Fan Nanfeng,Li Hui

Background Cancer cells can resist chemotherapy through various mechanisms, diminishing treatment outcomes. Research had indicated that combining miR-122 with doxorubicin (DOX) can improve hepatocellular carcinoma (HCC) therapy.Results To explore this, we created a one-pot co-delivery system, Fe-miR-122/DOX, by coordinating miR-122, DOX, and FeII ions into nanoparticles. These nanoparticles display uniform particle sizes, well-defined morphology, and exceptional colloidal stability in 10% FBS and 20% FBS solution over 24 h. When the ratio of DOX to miR-122 was set at 20:1, the loading efficiency of both drugs reached 54.7% and 55.5%, respectively. Cell experiments confirmed that Fe-miR-122/DOX efficiently delivers both miR-122 and DOX, enabling cytoplasmic delivery through lysosomal escape, facilitated by the positive charge of the nanoparticles. Functionally, miR-122 increases intracellular accumulation of DOX by downregulating P-glycoprotein (P-gp) expression, and it promotes apoptosis by downregulating B-cell lymphoma 2 (Bcl-2), which leads to the upregulation of Caspase-3. Additionally, Fe-miR-122/DOX disrupts cIAPs-mediated anti-apoptotic signals, downregulates PARP-1 expression, hinders DNA repair, promotes DNA fragmentation, enhances caspase-3 expression, and triggers programmed cell death, synergistically enhancing its antitumor efficacy. This synergistic mechanism disrupts DNA repair, amplifying DNA damage and apoptosis. Our cytotoxicity and apoptosis assays (with a HepG2 cell apoptosis rate of 85.98%) demonstrated the potent antitumor capability of Fe-miR-122/DOX.Conclusion sThis innovative system has demonstrated good biocompatibility and has the potential to transform HCC therapy. Future research could focus on optimizing the co-delivery system and assessing its efficacy in clinical trials.

CAS / MDL: 25316-40-9 7758-94-3
研究领域: 肿瘤学 · 药理学 · 分子生物学 · 纳米技术
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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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International Journal of Nanomedicine · 2023 · IF 8

Remarkable Boron Delivery Of iRGD-Modified Polymeric Nanoparticles For Boron Neutron Capture Therapy

Jiejian Chen,Qiyao Yang,Minchen Liu,Mengting Lin,Tiantian Wang,Zhentao Zhang,Xincheng Zhong,Ningning Guo,Yiying Lu,Jing Xu,Changsheng Wang,Min Han,Qichun Wei

Purpose Boron neutron capture therapy (BNCT) is an emerging binary radiotherapy, which is limited for application due to the challenge of targeted delivery into tumor nowadays. Here, we propose the use of iRGD-modified polymeric nanoparticles for active targeted delivery of boron and doxorubicin (DOX) in BNCT.Methods 10B-enriched BSH was covalently grafted to PEG-PCCL to prepare 10B-polymer, then surface-modified with iRGD. And, DOX was physically incorporated into polymers afterwards. Characterization of prepared polymers and in vitro release profile of DOX from polymers were determined by several methods. Cellular uptake of DOX was observed by confocal microscope. Accumulation of boron in cells and tissues was analyzed by ICP-MS. Biodistribution of DOX was studied by ex vivo fluorescence imaging and quantitative measurement. Tumor vascular normalization of Endostar for promoting delivery efficiency of boron on refractory B16F10 tumor was also studied.Results The polymers were monodisperse and spheroidal in water with an average diameter of 24.97 nm, which were relatively stable at physiological pH and showed a sustained release of DOX, especially at endolysosomal pH. Enhanced cellular delivery of DOX was found in iRGD-modified polymer group. Cellular boron uptake of iRGD-modified polymers in A549 cells was remarkably raised fivefold (209.83 ng 10B/106 cells) compared with BSH. The polymers represented prolonged blood circulation, enhanced tumor accumulation of 10B against BSH, and favorable tumor:normal tissue boron concentration ratios (tumor:blood = 14.11, tumor:muscle = 19.49) in A549 tumor-bearing mice 24 hrs after injection. Both fluorescence imaging and quantitative measurement showed the highest tumor accumulation of DOX at 24 hrs after injecting of iRGD-modified polymers. Improvement of vascular integrity and reduction of vascular mimicries were found after Endostar injection, and raised tumor accumulation of boron as well.Conclusion The developed nanoparticle is an inspiring candidate for the safe clinical application for BNCT.

研究领域: 癌症治疗 · 纳米技术 · 药学 · 生物医学工程
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BIOMEDICINE & PHARMACOTHERAPY · 2021 · IF 6.53

Glucose oxidase loaded Cu2+ based metal-organic framework for glutathione depletion/reactive oxygen species elevation enhanced chemotherapy

Jinzhi Xu,Yan Xu,Lixin Sun,Bei Lu,Xi Yan,Zhonghao Wang,Tong Zhang

Introduction The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine. Methods Here in our study, a Cu 2+ based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers. Results Our results showed that the GOx can catalyze glucose and produce H 2 O 2 . In the mean time, the Cu 2+ can react with GSH and then transform into Cu + , which resulted in GSH depletion. Afterwards, the produced Cu + and H 2 O 2 trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance. Discussion The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.

研究领域: 纳米医学 · 癌症治疗 · 药学科学 · 生物化学
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ACS Applied Nano Materials · 2026 · IF 5.8

Rolling Circle Amplification-Engineered DNA Nanoplatform for Synergistic In Vitro Breast Cancer Treatment Via Dual-Aptamer Programmed Co-Delivery of MoS2 Quantum Dots and DOX

Fatemeh Sasanipoor,Zhiqing Zhang,Ruyan Zhang,Gan Ning,Ting Zhou,Xiufeng Wang,Fang Wang

Achieving precise integration of molecular targeting, controlled drug release, and efficient photothermal conversion remains a critical challenge in the development of synergistic cancer nanotherapies. Here, we presented a programmable dual-aptamer DNA–MoS2 quantum dot (QDs) nanoplatform, constructed via multivariate hydrothermal synthesis and rolling circle amplification (RCA). Systematic optimization identified glutathione as the optimal sulfur source, resulting in the preparation of ultrasmall MoS2-QDs with strong 808 nm absorption, high colloidal stability, and excitation-dependent fluorescence. Covalent conjugation of these QDs to an RCA-derived DNA scaffold enabled high-density assembly of MUC1 and AS1411 aptamers and facilitated efficient doxorubicin (DOX) intercalation within GC-rich duplex regions. The resulting nanoplatforms demonstrated selective uptake by MCF-7 breast cancer cells, negligible internalization in normal fibroblasts, and DNase-responsive drug release. Upon near-infrared irradiation, the dual-aptamer assemblies elicited rapid photothermal heating, elevated intracellular reactive oxygen species (ROS), and mitochondrial dysfunction, generating a potent synergistic chemo-photothermal cytotoxicity. DOX-loaded RA@QDs further inhibited cancer cell migration, highlighting the enhanced therapeutic efficacy. This modular nanoplatform integrates the programmable DNA architecture, precise molecular targeting, enzyme-responsive drug delivery, and efficient photothermal activation, providing a scalable and mechanistically unified strategy for precision cancer nanomedicine.

CAS / MDL: 54827-17-7
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