ACS Applied Nano Materials
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2022
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IF 6.14
Yinghua Tao,Yucheng Li,Dandan Wei,Min Liang,Pengfei Ren,Jidong Dai,Tianzhu Zhang,Jiandu Lei,Peidang Liu
Multifunctional nanomaterials with diagnostic and therapeutic capabilities offer promising customized nanomedicines for cancers. However, achieving good execution of these functions in vivo employing a single nanoframework remains challenging, and only a few of these magnetic nanocarriers have been validated for clinical use. In this study, based on biocompatibility and remarkable multifunctionalities, we describe a novel approach to synthesize small Fe3O4 nanoparticles conjugated with natural polysaccharide pectin and assembled into a pH-responsive T1-weighted magnetic resonance imaging contrast agent, Fe3O4@PD, for better chemotherapeutic efficacy. In vitro studies revealed that the conjugated doxorubicin (DOX) was quickly released in the tumor microenvironment by cleavage of the acid-sensitive acylhydrazone bond at a release rate of 89.72% and exerted a considerable inhibitory effect on breast cancer cells. In vivoT1-weighted images of mice showed that Fe3O4@PD displayed darkening to brightening contrast enhancement at tumor sites, and the relative signal-to-noise ratio of the tumor site reached its maximum (increased to about 2.27-fold) for distinguishing the normal and tumor tissues. Thus, this Fe3O4@PD-based system has the potential to be a multifunctional nanodrug delivery system, and as a smart theragnostic platform, it has broad application prospects in clinical and biological works, such as cell-based diagnostics and in vivo medication monitoring.
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高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 20
·3291-3302
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IF 5.047
Kaiwu Cheng,Yu Zhang,Yaojia Li,Zhiguo Gao,Fanghui Chen,Kai Sun,Peijing An,Chen Sun,Yong Jiang,Baiwang Sun
The multi-therapy modality is based on the combination and synergy of multiple single treatment modalities and materials chemistry. Herein, a novel pH-responsive doxorubicin (DOX) delivery system based on hollow mesoporous silica nanoparticles (HMSNs) was constructed, which was designed to treat cancer via synergistic chemotherapy and starvation therapy. Logically, starvation therapy could improve the therapeutic efficiency by sensitizing the drug molecules and activating the chemotherapy; glucose oxidase (GOX) coupled to the surface of HMAN deprived the cancer cells of glucose for starvation therapy and increased the abnormality of the tumor microenvironment by locally reducing the pH, aggravating hypoxia and promoting the concentration of poisonous H2O2. Increased acidity could accelerate the depolymerization of pH-sensitive polyelectrolyte multilayers (PEM) wrapped on the most external surface, causing the spatial control of DOX release within tumor cells. Detailed physical characterization certified the successful synthesis of DOX/GOX@HMSN-PEM, which was approximately 180 nm in diameter. In vitro experiments demonstrated that GOX could effectively promote drug release, and DOX/GOX@HMSN-PEM possessed high drug loading rate and stability. Excellent cellular uptake performances were revealed by confocal laser scanning microscopy (CLSM). The positively charged nanoparticles could specifically target the cancer cells overexpressing negative charges. In addition, they were found to have an excellent effect on the cytotoxicity and apoptosis. The promoted drug release via combined starvation therapy and drug therapy suggests that this novel type of pH-responsive hollow mesoporous silica nanoparticles may serve as a new drug delivery system for cancer treatment.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2018
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IF 3.862
Huanan Li,Chenhao Yu,Jingni Zhang,Qianyan Li,Hai Qiao,Zhigang Wang,Deping Zeng
Nanoemulsions as synergists of high intensity focused ultrasound (HIFU) have been widely investigated, since they possess huge potential for improving the efficiency to ablate tumor. However, their clinical applications are limited due to the unsatisfactory phase-transition effect of nanoemulsions during the process of generating nanobubbles . Herein, a novel synergist for HIFU therapy was designed by encapsulating 1,1,2-trichlorotrifluoroethane (CFC) into pH-sensitive pullulan-doxorubicin (Pu-DOX/CFC) nanoparticles . These Pu-DOX/CFC nanoemulsions, with moderate vaporization temperature threshold of 47 °C, could provide favorable phase-transition effect, thus facilitating HIFU energy deposition. Meanwhile, Pu-DOX/CFC nanoemulsions could effectively deliver DOX/CFC to the tumor site and carry out combined therapy. The in vitro and in vivo results confirmed that Pu-DOX/CFC nanoemulsions notably enhanced both ablation and therapeutic efficiency comparing with other synergists. In conclusion, Pu-DOX/CFC nanoemulsions might serve as a novel synergist for HIFU therapy, and possess great potential in clinical implication.
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PubMed
高影响因子
DRUG DELIVERY
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2018
·
IF 3.095
Yiwen You,Zhiyuan Xu,Yun Chen
HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs. There is evidence indicating that conjugation of trastuzumab with chemotherapy drugs, such as doxorubicin (DOX), for multiple targets could be more effective. However, incomplete penetration into tumors has been noted for those conjugates. Compared to an antibody, peptides may represent an attractive alternative. For HER2, a similar potency has been observed for a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH2 (AHNP, disulfide-bridged) and full-length trastuzumab. Thus, a peptide, GPLGLAGDDYCDGFYACYMDV-NH2, which consists of AHNP and an MMP-2 cleavable linker GPLGLAGDD, was first designed, followed by conjugation with DOX via a glycine residue at the N-terminus to form a novel DOX-peptide conjugate MAHNP-DOX. Using HER2-positive human breast cancer cells BT474 and SKBR3 as in vitro model systems and nude mice with BT474 xenografts as an in vivo model, this conjugate was comprehensively characterized, and its efficacy was evaluated and compared with that of free DOX. As a result, MAHNP-DOX demonstrated a much lower in vitro IC50, and its in vivo extent of inhibition in mice was more evident. During this process, enzymatic cleavage of MAHNP-DOX is critical for its activation and cellular uptake. In addition, a synergistic response was observed after the combination of DOX and AHNP. This effect was probably due to the involvement of AHNP in the PI3K–AKT signaling pathway, which can be largely activated by DOX and leads to anti-apoptotic signals.
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PubMed
高影响因子
Nano Research
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2018
·Vol. 11
·期 6
·3385-3395
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IF 7.994
Wang Wei,Zhao Yang,Yan Bei-Bei,Dong Liang,Lu Yang,Yu Shu-Hong
Calcium carbonate-doxorubicin@silica-indocyanine green nanospheres with high uniformity and monodispersity were designed and synthesized, in order to provide a photo-triggered strategy for drug-resistant cancer therapy. Under near-infrared laser irradiation, the nanospheres transformed laser power into local heat and reactive oxygen species via the connected indocyanine green molecule, thus exhibiting photothermal and photodynamic effects. Moreover, the photo-triggered drug release based on calcium-assisted silica degradation was observed, endowing the nanospheres with chemotherapeutic properties. Finally, combined therapeutic effects against drug-resistant human breast cancer cells were successfully obtained. These photo-triggered materials based on calcium carbonate could provide a promising platform for enhanced multimodal cancer therapies.
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高影响因子
RSC Advances
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2016
·Vol. 6
·期 56
·50985-50992
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IF 3.289
Ruo-Mei Wang,Qian Liu,Yu Zhang,Zhangyong Hong,He-Fang Wang
Smart drug carriers with intrinsic photoluminescence (PL) tracking of controllably released drugs are of great significance to indicate in real-time where, when and how the drug was released. Herein, we present a novel multifunctional poly(N-isopropylacrylamide)–Mn–ZnS (PMZS) nanocomposite for thermo- and pH-controlled release of doxorubicin (Dox) and real-time tracking of the released Dox in a PL-enhanced manner. The simple coupling of Mn–ZnS quantum dots and poly(N-isopropylacrylamide) resulted in the unique thermo- and pH-responsive PL of PMZS. There was a much higher PL intensity at 37 °C than 25 °C and a much higher PL intensity at weakly acidic pH than at neutral pH, which is promising for PL imaging in tumor microenvironments. The PL of the PMZS composite was greatly quenched upon loading of Dox (the loading content and encapsulation efficiency of PMZS composites toward Dox were 15.2% and 84.1%, respectively), but was gradually restored with the controllable release of Dox, and the restored PL intensity was proportional to the cumulative amount of Dox released. The versatility of the PMZS composite as an effective Dox carrier and real-time PL-enhanced tracking of the controllably released Dox were further proved by cell viability assays and in vitro cell imaging experiments. The simple PMZS nanocomposite was easily-synthesized, biocompatible, and promising for PL tracking of when, where and how Dox was released.
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高影响因子
Nanoscale
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2017
·Vol. 9
·期 34
·12533-12542
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IF 7.367
Cheng Gao,Fan Tang,Guiyi Gong,Jianxiang Zhang,Maggie P. M. Hoi,Simon M. Y. Lee,Ruibing Wang
In order to realize a combination of chemotherapy and selective drug release into tumor cells, novel pH-sensitive prodrugnanoparticles were designed and prepared via the self-assembly of a synthetic amphiphilic macromolecular prodrug for the selective co-delivery of doxorubicin (Dox) and curcumin (Cur). Dox was covalently conjugated to the oxidized sodium alginate through a Schiff base reaction to produce an amphiphilic macromolecular prodrug, and the prodrug was subsequently self-assembled into nanoparticles (Dox-NPs) in an aqueous solution, which were responsive to the acidic environment in tumor cells. Additionally, a second chemotherapeutic agent, Cur, was encapsulated in the core of nanoparticles (Cur–Dox-NPs) via hydrophobic effects, with a significant drug loading capacity. Cur–Dox-NPs exhibited an efficient release of both Dox and Cur in acidic media and further studies of their intracellular uptake and drug release confirmed that Dox-NPs were easily taken up by cells and selectively released the drug into the human breast cancer cell line MCF-7. In vitro cytotoxicity studies of the NPs showed a remarkable efficacy against MCF-7 cell lines, whereas an improved safety profile was observed in the human breast epithelial cell line MCF-10A. Furthermore, in vivo studies in zebrafish further confirmed an efficient absorption of Dox-NPs. In vivo cardiotoxicity experiments on a zebrafish model showed that Dox-NPs exhibited an improved cardiotoxicity profile in comparison with free Dox. This study demonstrated that this novel pH-sensitive prodrug-nanoparticle system may provide a simple and efficient platform for the selective co-delivery of multiple drugs to tumor cells.
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PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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2016
·Vol. 40
·期 10
·8397-8407
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IF 3.277
Beibei Lu,Lei Li,Jianning Wu,Lulu Wei,Jun Hou,Zhiyong Liu,Xuhong Guo
Well-defined dual pH and temperature responsive triblock star-shaped amphiphilic copolymers of β-cyclodextrin-g-poly(2-hydroxyethylmethacrylate)-b-poly(N-isopropylacrylamide)-b-poly(2-(dimethylamino)ethylmethacrylate) (β-CD-g-(PHEMA-b-PNIPAM-b-PDMAEMA)) were synthesized by the combination of reversible addition–fragmentation chain transfer (RAFT) polymerizations. The chemical structures and compositions of these copolymers were characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), and gel permeation chromatography (GPC) measurements. Subsequently, the obtained triblock copolymers could self-assemble into micelles in aqueous solution owing to their amphiphilic property resulting from the hydrophobic β-CD core and the hydrophilic PHEMA, PNIPAM, and PDMAEMA segments, which were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The triblock copolymer nanoparticles exhibited two separate lower critical solution temperatures (LCSTs) and these triblock copolymers in aqueous solutions were investigated at the different pH values of 5.0 and 7.4 as doxorubicin (DOX) delivery systems for controlled release. Polymeric micelles exhibited a pH controlled release performance. Investigation of DOX release from the micelles indicated that the release rate of the drug could be effectively controlled by altering the pH, encapsulating DOX in neutral surroundings (blood circulation or extracellular matrix) and triggering DOX release in acidic surroundings (intracellular endosomes). CCK-8 assays and confocal laser scanning microscopy (CLSM) against HeLa cells indicated that the polymeric micelles themselves had no associated cytotoxicity and possessed good biodegradability and biocompatibility and that the micelles identified the location of the DOX in the HeLa cells. On the other hand, the DOX-loaded micelles possessed a high cytotoxicity to HeLa cells and exhibited inhibition of the proliferation of HeLa cells. Hence, this type of biodegradable, biocompatible, and stimuli-responsive copolymer could serve as a promising material for drug delivery.
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高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
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2017
·Vol. 19
·期 6
·1-13
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IF 2.02
Zhang Ran,Wang Shi-Bin,Wu Wen-Guo,Kankala Ranjith Kumar,Chen Ai-Zheng,Liu Yuan-Gang,Fan Jing-Qian
Recently, targeted drug delivery systems (TDDS) have offered a great potential and benefits towards the anti-tumor drug delivery. In this work, we designed the TDDS using a biocompatible poly(ethylene glycol)-poly( β -amino esters) amphiphilic block copolymer (PEG-PAEs) synthesized by Michael addition polymerization for combinatorial therapy. Further, the chemotherapeutic agents’ doxorubicin (DOX) and AS1411 DNA aptamer (Apt) are encapsulated in the PEG-PAEs NPs (PDANs) for co-delivery therapeutics. PDANs have shown the monodisperse spherical shape, smooth surface with a net positive charge (average diameter—183.1 ± 27.2 nm, zeta potential—31.2 ± 6.3 mV), and good colloidal stability (critical micelle concentration of PEG-PAEs is about 6.3 μg/mL). The pH-sensitive PAEs endowed PDANs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the localization and cytotoxicity of DOX. AS1411 Apt conjugated PDANs precisely targeted nucleolin and their uptake correlates to a significant activity enhancement only in tumor cells (MCF-7) but not in normal cells (MCF-10A). Thus, PDANs can be a very promising targeted drug delivery platform for effective breast cancer therapy.
Scheme 1 Schematic illustration of the preparation and cellular uptake of targeted co-delivery system
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高影响因子
BIOMATERIALS
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2015
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IF 8.557
Leyong Zeng,Yuanwei Pan,Ying Tian,Xin Wang,Wenzhi Ren,Shouju Wang,Guangming Lu,Aiguo Wu
The combination therapy has exhibited important potential for the treatment of cancers, especially for drug-resistant cancers. In this report, bi-functional nanoprobes based on doxorubicin (DOX)-loaded NaYF 4 :Yb/Tm–TiO 2 inorganic photosensitizers (FA-NPs-DOX) were synthesized for in vivo near infrared (NIR)-triggered inorganic photodynamic therapy (PDT) and enhanced chemotherapy to overcome the multidrug resistance (MDR) in breast cancers. Using the up-conversion luminescence (UCL) performance of NaYF 4 :Yb/Tm converting near-infrared (NIR) into ultraviolent (UV) lights, reactive oxygen species (ROS) were triggered from TiO 2 inorganic photosensitizers for PDT under the irradiation of a 980 nm laser, by which the deep-penetration and low photo-damage could be reached. Moreover, nanocarrier delivery and folic acid (FA) targeting promoted the cellular uptake, and accelerated the release of DOX in drug-sensitive MCF-7 and resistant MCF-7/ADR cells. The toxicity assessment in vitro and in vivo revealed the good biocompatibility of the as-prepared FA-NPs-DOX nanocomposites . By the combination of enhanced chemotherapy and NIR-triggered inorganic PDT, the viability of MCF-7/ADR cells could decrease by 53.5%, and the inhibition rate of MCF-7/ADR tumors could increase up to 90.33%, compared with free DOX. Therefore, the MDR of breast cancers could be obviously overcome by enhanced chemotherapy and NIR-triggered inorganic PDT of FA-NPs-DOX nanocomposites under the excitation of a 980 nm laser.
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PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2017
·
IF 4.164
Hao Zhang,Xiaogang Luo,Hu Tang,Mingming Zheng,Fenghong Huang
The aim of this study is to develop transparent maghemite/cellulose nanocomposite membranes with high porosity, high adsorption capacity and controlled release of doxorubicin to be used as a candidate for wound dressing. The membranes were fabricated by a tape casting method through blending a homogeneous dispersion of citrate coated maghemite nanoparticles and cellulose in the NaOH/urea aqueous solution system. The prepared membranes were characterized by Light transmittance measurements, Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray Diffractometry (XRD), Differential scanning calorimetry (DSC), Tensile tests and Vibrating sample magnetometer (VSM). Furthermore, porosity, swelling behavior, water loss ratio and Bovine serum albumin adsorption capacity were evaluated. Drug loading and release was investigated using doxorubicin hydrochloride as a model drug. In vitro cytotoxicity and cells morphology assays of cells growth and proliferation were also studied. This study served as a demonstration of the feasibility of maghemite/cellulose nanocomposite membranes for loading and release of bioactive compounds as a candidate for wound dressing.
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高影响因子
Cancer Nanotechnology
·
2024
·Vol. 15
·期 1
·1-15
·
IF 4.5
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.
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高影响因子
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