International Journal of Nanomedicine
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2024
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IF 6.6
Xinbo Zhang,Bin Xu,Jiangwei Ni,Yucheng Xiang,Zhifeng He
Purpose The chemotherapeutic agent doxorubicin (DOX) is limited by its cardiotoxicity, posing challenges in its application for non-small cell lung cancer (NSCLC). This study aims to explore the efficacy of polydopamine/Au nanoparticles loaded with DOX for chemotherapy and photothermal therapy in NSCLC to achieve enhanced efficacy and reduced toxicity.Methods Hollow polydopamine (HPDA)/Au@DOX was synthesized via polydopamine chemical binding sacrificial template method. Morphology was characterized using transmission electron microscopy, particle size and potential were determined using dynamic light scattering, and photothermal conversion efficiency was assessed using near-infrared (NIR) thermal imaging. Drug loading rate and in vitro drug release were investigated. In vitro, anti-tumor experiments were conducted using CCK-8 assay, flow cytometry, and live/dead cell staining to evaluate the cytotoxicity of HPDA/Au@DOX on A549 cells. Uptake of HPDA/Au@DOX by A549 cells was detected using the intrinsic fluorescence of DOX. The in vivo anti-metastasis and anti-tumor effects of HPDA/Au@DOX were explored in mouse lung metastasis and subcutaneous tumor models, respectively.Results HPDA/Au@DOX with a particle size of (164.26±3.25) nm, a drug loading rate of 36.31%, and an encapsulation efficiency of 90.78% was successfully prepared. Under 808 nm laser irradiation, HPDA/Au@DOX accelerated DOX release and enhanced uptake by A549 cells. In vitro photothermal performance assessment showed excellent photothermal conversion capability and stability of HPDA/Au@DOX under NIR laser irradiation. Both in vitro and in vivo experiments demonstrated that the photothermal-chemotherapy combination group (HPDA/Au@DOX+NIR) exhibited stronger anti-metastatic and anti-tumor activities compared to the monotherapy group (DOX).Conclusion HPDA/Au@DOX nanosystem demonstrated excellent photothermal effect, inhibiting the growth and metastasis of A549 cells. This nanosystem achieves the combined effect of chemotherapy and photothermal, making it promising for NSCLC treatment.
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高影响因子
ANNALS OF BIOMEDICAL ENGINEERING
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2016
·Vol. 44
·期 11
·3372-3383
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IF 2.887
Xie Bei,Peng Jian,Wang Shuo,Zhang Xing,Nie Hemin
The combination of gene therapy and chemotherapy has showed increased therapeutic efficacy in the treatment of cancers, but it is not well investigated about the actual coordination pattern between therapeutic gene and chemical drug. In this work, p53/BPEI-β-CD/AD-dox complex was fabricated and employed to investigate the interaction manner between p53 and doxorubicin (Dox). Briefly, branched polyethylenimine (BPEI) was conjugated with β-cyclodextrin hydrate (β-CD) to form BPEI-β-CD backbone, and p53 plasmid was condensed by positively charged BPEI via electrostatic interaction, while Dox was first conjugated with adamantine (AD) and then assembled with BPEI-β-CD backbone via the host–guest interaction. It was found that the BPEI-β-CD backbone possessed high endocytosis efficiency but low cytotoxicity. Moreover, p53/BPEI-β-CD/AD-dox complex released Dox and enabled the expression of p53 gene in a sequential manner, and the released Dox and expressed p53 gene showed successive inhibition of the growth of HeLa cells in vitro . With the ability to co-deliver chemical drug and therapeutic gene and exert their inhibitory actions on tumor cell growth in a sequential manner, this DNA/BPEI-β-CD/AD-drug complex via electrostatic interaction and host–guest assembly not only achieved long-term efficacy in inhibiting tumor cell growth but also can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for other purposes.
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JOURNAL OF MATERIALS SCIENCE
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2016
·Vol. 51
·期 20
·9367-9383
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IF 2.302
Chen Fangfang,Chen Heng,Duan Xiao,Jia Jiqiong,Kong Jie
In this contribution, we reported a novel strategy to synthesize porous molecularly imprinted polymers (MIPs) of anticancer drug of doxorubicin hydrochloride (DOX) using reduction-cleavable hyperbranched polymers containing disulfide bonds (ds-HP-alkyne). The porous MIPs (MIP-DOX-HP) possess enhanced specific surface area and porosity by the incorporation of cleavable hyperbranched polymers from the copper(I)–catalyzed azide–alkyne click chemistry. In comparison to MIPs synthesized without using ds-HP-alkyne, MIP-DOX-HP exhibits more regular and open porous structures, which increase the loading and controlled release abilities of DOX anticancer drug. Under optimized pH condition, the total cumulative release amount of DOX at equilibrium is as high as 2134 and 1249 µg for MIP-DOX-HP and MIP-DOX, respectively. The effective and robust strategy for synthesizing MIPs using cleavable hyperbranched polymers is helpful for extending applications of MIPs in drug delivery and target-activated release systems.
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JOURNAL OF CONTROLLED RELEASE
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2016
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IF 7.441
Jiangshan Wan,Shinan Geng,Hao Zhao,Xiaole Peng,Qing Zhou,Han Li,Ming He,Yanbing Zhao,Xiangliang Yang,Huibi Xu
Doxorubicin (DOX)-induced co-assembling nanomedicines (D-PNA x ) with temperature-sensitive PNA x triblock polymers have been developed for regional chemotherapy against liver cancer via intratumoral administration in the present work. Owing to the formation of insoluble DOX carboxylate , D-PNA x nanomedicines showed high drug-loading and entrapment efficacy via a simple mixing of doxorubicin hydrochloride and PNA x polymers. The sustained releasing profile of D-PNA100 nanomedicines indicated that only 9.4% of DOX was released within 1 day, and 60% was released during 10 days. Based on DOX-induced co-assembling behavior and their temperature sensitive in-situ -forming hydrogels, D-PNA100 nanomedicines showed excellent antitumor activity against H22 tumor using intratumoral administration. In contrast to that by free DOX solution (1.13 ± 0.04 times at 9 days) and blank PNA100 (2.11 ± 0.34 times), the tumor volume treated by D-PNA100 had been falling to only 0.77 ± 0.13 times of original tumor volume throughout the experimental period. In vivo biodistribution of DOX indicated that D-PNA100 nanomedicines exhibited much stronger DOX retention in tumor tissues than free DOX solution via intratumoral injection. D-PNA100 nanomedicines were hopeful to be developed as new temperature sensitive in-situ -forming hydrogels via i.t. injection for regional chemotherapy.
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Integrative Biology
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2016
·Vol. 8
·期 9
·956-967
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IF 3.371
Li Lin,Tian Lu,Zhao Wenjing,Li Yingqi,Yang Binsheng
A successful drug delivery device for cancer chemotherapy should ideally be able to load drugs highly, bring the drug preferentially into tumor cells and reduce its distribution in normal tissue to enhance therapeutic efficacy. To this purpose, a novel protocol for DOX-loaded PEGylated nanodiamond (ND-PEG–DOX/NaAc, NPDA) was fabricated using sodium acetate medium. The NPDA nanoparticles exhibited a maximum loading efficiency (99 wt%) with ultra-low drug leakage (7 wt%). Examination by confocal microscope and flow cytometer showed that the NPDA uptake by cells was time-dependent, with a slow and sustained drug release from the lysosomes at a low pH. Also, when CHO (a normal cell) and MCF-7 (a cancer cell) were treated with NPDA, the results demonstrated that NPDA preferentially accumulated much more in tumor cells than in normal cells, which implied that NPDA has the ability to selectively kill tumor cells. In addition, NPDA can inhibit the migration and proliferation of tumor cells and change the cell cycle compared to the free drug. Outcomes from this work suggest that NPDA would be a promising drug delivery platform and the preparation of such a drug delivery system will also have implications in improving the biomedical applications of smart nanodiamond carriers.
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JOURNAL OF MATERIALS CHEMISTRY
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2012
·Vol. 22
·期 41
·22290-22300
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IF 5.968
Tao Xing,Xianzhu Yang,Feng Wang,Bin Lai,Lifeng Yan
A near infrared fluorescent polymeric drug delivery system (NIRF DDS) with pH-responsive drug release properties has been designed and developed. This material was prepared by chemical conjugation of the anticancer drug doxorubicin and hydrophobic aminocyanine dye to triblock copolypeptide via hydrazone and amide bonds, respectively. Conjugation with aminocyanine shows almost no toxicity of the material, while conjugation with doxorubicin induces pronounced toxicity on the original biocompatible material. The pH sensitive drug release nature of the near infrared fluorescent polymeric drug (NIRF prodrug) was confirmed by accelerated drug release at pH of 5.0 via an in vitro drug release experiment and gradual drug cleavage from the NIRF prodrug during a confocal laser scanning microscopic (CLSM) experiment. The CLSM experiment also reveals that the released drug subsequently migrated to the nucleus, while the polymeric residue still remained in cytoplasm, indicating that the as-prepared polymer can be a promising candidate for theranosis of cancer.
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ACS Applied Materials & Interfaces
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2015
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IF 6.723
Yanqin Huang,Caixia Song,Huichang Li,Rui Zhang,Rongcui Jiang,Xingfen Liu,Guangwei Zhang,Quli Fan,Lianhui Wang,Wei Huang
Hyaluronidase (HAase) is becoming a new type of tumor marker since it has been demonstrated to be overexpressed in various kinds of cancer cells. In this study, we described a novel fluorescence method for sensitive, rapid, and convenient HAase detection and tumor-targeting drug delivery and imaging, using a probe prepared by electrostatic assembly of a cationic conjugated polymer (CCP) and anionic hyaluronan (HA) conjugated with the anticancer drug doxorubicin (Dox). The CCP we used was poly{[9,9-bis(6′-(N,N,N-diethylmethylammonium)hexyl)-2,7-fluorenylene ethynylene]-alt-co-[2,5-bis(3′-(N,N,N-diethylmethylammonium)-1′-oxapropyl)-1,4-phenylene]} tetraiodide (PFEP). HA is a natural mucopolysaccharide that can be hydrolyzed by HAase into fragments with low molecular weights. In the PFEP/HA-Dox complex, the fluorescence of PFEP was efficiently quenched due to electron transfer from PFEP to Dox. After the PFEP/HA-Dox complex was exposed to HAase or was taken up by cancer cells through the specific binding between HA and CD44 receptor, HA was degraded by HAase to release the Dox, leading to the recovery of PFEP fluorescence to the “turn-on” state. Moreover, the degree of fluorescence recovery was quantitatively correlated with the concentrations of HAase. Compared with many previously reported methods, our work did not require laborious multiple modifications of HA that may affect the activity of HAase. This point, combined with the excellent optoelectronic property of conjugated polymer, endowed this method with high sensitivity (detection limit: 0.075 U/mL), high specificity, and rapid response, making it applicable for reliable and routine detection of HAase. This fluorescent probe was successfully utilized to detect HAase levels in human urine samples; furthermore, it can also be employed as a multifunctional system by realizing tumor-targeting drug delivery and cell imaging simultaneously. The development of this fluorescence method showed promising potential for early tumor diagnosis and therapy based on HAase detection.
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Journal of Materials Chemistry B
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2013
·Vol. 1
·期 32
·3906-3917
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IF 0
Haijun Shen,Hui Shi,Meng Xie,Kun Ma,Bo Li,Song Shen,Xinshi Wang,Yi Jin
We engineered advanced biodegradable chitosan–alginate BSA-gel-capsules and demonstrated their applicability for the treatment of lung diseases. The pH-controlled loading and release of doxorubicin (DOX) was demonstrated. After treatment with DOX-loaded chitosan–alginate BSA-gel-capsules, effective cytotoxicity against B16F10 cells in vitro and higher efficacy of the pulmonary melanoma in vivo were revealed. In particular, the real-time biodistribution of DOX from DOX-loaded capsules was investigated for the first time, indicating the metabolism of capsules from the lung. These engineered capsules present new opportunities en route to the development of polyelectrolyte microcapsules for drug delivery.
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Particuology
·
2025
·
IF 4.3
Limei Zhang,Huatai Zhu,Peng Ye,Yuting Ren,Hongyu Wang,Jiandu Lei,Jing He
Combining drug delivery technologies with chemotherapeutic drugs is very attractive in terms of enhancing antitumor efficacy and reducing toxicity. Alginate microspheres stand out in the field of drug delivery due to their biocompatibility and high conversion rate. However, there are certain drawbacks in their preparation technology and further research is needed on how to prepare alginate microspheres with uniform particle size using high-viscosity sodium alginate solution. Therefore, this study proposed a novel microfluidic membrane emulsification technique for the preparation of alginate microspheres from high-viscosity sodium alginate solution. A tumor microenvironment-responsive colorectal cancer-targeted oral drug delivery system was constructed using a disulfide-bonded coupling of honokiol and doxorubicin as a model drug to achieve precise targeting, efficiency enhancement and toxicity reduction. The results showed that the prepared microspheres were relatively homogeneous in particle size. The in vitro model showed the high stability of the microspheres in the gastric acid environment and the colon-targeted release characteristic. And the system triggered the breakage of redox bonds and the precise release of the drug, showing good antitumor activity. This study contributes to the construction of drug delivery systems and the study of colon cancer treatment, which has a promising application.
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APPLIED CATALYSIS B-ENVIRONMENTAL
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2021
·
IF 19.503
Haoyang Fu,Ruizhao Wang,Qianyu Xu,Minwang Laipan,Chenliu Tang,Weixian Zhang,Lan Ling
Typical antineoplastic agent doxorubicin (DOX) contamination is a major environmental concern and its efficient purification remains a daunting challenge so far. This work explored the potential of Fe/Pd-doped graphite carbon nitride (g-C 3 N 4 @Fe/Pd) for DOX removal from water, involving the removal performance, mechanism, and pathway. Structural characterization of g-C 3 N 4 @Fe/Pd showed that the metallic Pd clusters are decorated on the surface of uniformly distributed iron nanoparticles (~ 28 nm) on g-C 3 N 4 . The existence of g-C 3 N 4 effectively relieved the agglomeration and overgrowth of iron nanoparticles, the strong coupling effect among the Fe, Pd and N demonstrates the excellent DOX removal performance (k = 0.115 min −1 ) with versatility under different initial concentrations (30–150 mg/L) and material dosages (0.1–0.4 g/L). Three possible degradation pathways of DOX were proposed, where catalytic saccharide moiety elimination is the primary pathway. Importantly, intermediates exhibit lower toxicity and the final degradation product is efficiently adsorbed by g-C 3 N 4 @Fe/Pd.
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Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 29
·5046-5058
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IF 4.872
Lin Li,Lu Tian,Yongli Wang,Wenjing Zhao,Fangqin Cheng,Yingqi Li,Binsheng Yang
Nanodiamond as a carrier for transporting chemotherapy drugs has emerged as a promising strategy for treating cancer. However, several factors have limited its extensive applications in biology, such as low drug loading, tending to aggregate and high drug loss under physiological conditions. In this work, to ensure a high drug capacity and low drug leakage in blood circulation, and especially to ensure that it is delivered to the tumor region, a smart pH-responsive drug delivery system is designed and prepared using doxorubicin (DOX) adsorbed onto PEGylated nanodiamond in sodium citrate medium (ND–PEG–DOX/Na3Cit, NPDC). The system can significantly enhance cellular uptake to exert a therapeutic effect in comparison to the free drug. And more importantly, DOX was released in a sustained and pH-dependent manner, exhibiting excellent stability under physiological conditions. In addition, NPDC could enter into cells via both the clathrin- and caveolae-mediated endocytosis pathways, and then the dissociated DOX migrated into the nucleus to block the growth of cancer cells. Furthermore, NPDC can significantly inhibit cell migration and change the cell cycle. Excitingly, the NPDC system was very smart for the effective enrichment at the tumor site in vivo and enhancing antitumor efficiency with low toxicity beyond conventional DOX treatment in cancer cells and a nude mouse model. So this study introduces a simple and effective strategy to design a promising drug delivery platform for improving the biomedical applications of the smart nanodiamond carriers.
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Journal of Materials Chemistry B
·
2020
·Vol. 9
·期 5
·1336-1350
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IF 5.344
Jiatao Yang,Qiuyi Li,Rui Zhou,Minglu Zhou,Xi Lin,Yucheng Xiang,Dandan Xie,Yuan Huang,Zhou Zhou
Distant organ metastasis is the main cause of death in breast cancer patients. Evidences have shown that mitochondria also play a crucial role in tumor metastasis, except for as apoptosis center. However, the treatment of tumor growth and metastasis was reported to be limited by mitochondria-associated protein Bcl-2, which are gatekeepers of apoptosis and are found to reside in mitochondria mainly. Herein, we designed a mitochondria-targeting doxorubicin delivery system as well as a mitochondrial distributed Bcl-2 function-converting peptide NuBCP-9 delivery system, which are both based on N-(2-hydroxypropyl)methacrylamide copolymers, to achieve a synergistic effect on tumor regression and metastasis inhibition by combination therapy. After mitochondria were damaged by mitochondria-targeting peptide-modified doxorubicin, apoptosis was effectively enhanced by mitochondrial specifically distributed NuBCP-9 peptides, which converted Bcl-2 function from anti-apoptotic to pro-apoptotic and paved the way for the development of mitochondrial impairment. The combination treatment exhibited significant damage to mitochondria, including excess reactive oxygen species (ROS), the permeabilization of mitochondrial outer membrane (MOMP), and apoptosis initiation on 4T1 breast cancer cells. Meanwhile, besides enhanced tumor growth suppression, the combination treatment also improved the inhibition of 4T1 breast cancer metastasis both in vitro and in vivo. By increasing the expression of cytochrome C and decreasing the expression of Bcl-2, metal matrix protease-9 (MMP-9) as well as vascular endothelial growth factor (VEGF), the combination treatment successfully decreased 84% lung metastasis. Overall, our work provided a promising strategy for metastatic cancer treatment through mitochondria-targeting anti-cancer drug delivery and combination with mitochondrial distributed Bcl-2 function-converting peptide.
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