MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2019
·Vol. 14
·期 1
·1-10
·
IF 3.159
Tian Yefei,Lei Miao
Photothermal therapy (PTT) that utilizes phSUPPotothermal conversion agents (PTC) to ablate tumor under NIR light irradiation has attracted increasing attention due to its excellent therapeutic efficacy and improved target selectivity. Herein, a novel core-shell nanoparticle based on disulfide-crosslinked poly(methacrylic acid) (PMAA) layer coated polydopamine (PDA) particle has been successfully synthesized by precipitation polymerization. For these PDA@PMAA composite nanoparticles, PDA core exhibits high photothermal efficacy, meanwhile, the redox-labile PMAA shell serves as carriers to encapsulate anticancer drugs and selectively release them. Due to the characteristic of the disulfide bond, PMAA shell occurs at selective degradation as well as controlled drug release upon entering cancer cells. Moreover, the DOX-loaded PDA@PMAA nanoparticles demonstrated a synergistic effect, which shows a significantly improved inhibition effect against cancer cells by the combination of photothermal therapy and traditional chemotherapy with low drug dosage and short laser irradiation in an in vitro study.
研究领域:
纳米医学
·
癌症治疗
·
材料科学
·
聚合物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Zehao Li,Jianchao Li,Dazhuang Wang,Cong Li,Kexin Zhang,Lihong Wang,Chao Shen,Zhihang Li,Yating Ji,Lijiang Chen
In order to construct an oral drug delivery system to improve the bioavailability of drugs. This project prepared a compound drug carrier that combines the advantages of biological carriers and synthetic carriers. This oral drug delivery system (YP-MPA-ZnO-DOX) consists of yeast microcapsules (YP) and DOX-loaded ZnO nanoparticles modified with 3-mercaptopropionic acid (MPA). The average particle size of the particles was 4620 nm and the potential was about +22.7 mV as measured by particle size and zeta potential. The in vitro release experiments showed that the DOX release rate of YP-MPA-ZnO-DOX in simulated gastric fluid (SGF) for 11 h was about 20 %. The cumulative release rate of DOX in simulated intestinal fluid (SIF) for 11 h was about 10 %, indicating that YP-MPA-ZnO-DOX could resist gastrointestinal fluid erosion and had drug retention effects. Meanwhile, in the simulated tumor environment, the cumulative release of DOX could reach 97.6 %, almost completely released. Cellular experiments demonstrated that the inhibition rate of YP-MPA-ZnO-DOX on HepG2 and HCT116 cells was close to 75 % after 48 h, which was much higher than that of DOX alone. Pharmacokinetic studies demonstrated that compared with free DOX, the half-life of YP-MPA-ZnO-DOX could be prolonged to 13.621 ± 0.09 h, which significantly improved the bioavailability of DOX after oral administration. Utilization after oral administration of DOX. In conclusion, YP-MPA-ZnO-DOX provides a promising application for oral DOX.
研究领域:
药剂学
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纳米技术
·
癌症研究
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药物递送系统
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Rong Liu,Huicong Zhang,Fangrong Zhang,Xuandong Wang,Xiaolong Liu,Yun Zhang
The nanoplatform of synergistic chemo-photothermal therapy has superior advantages on antitumor. It is urgently needed to explore novel nanocarrier for improving photothermal performance in drug delivery process. Herein, we synthesized polydopamine doped mesoporous silica-coated reduced graphene oxide (rGO/MSN/PDA) by simply adding dopamine hydrochloride into the oil-water biphasic reaction system as a multifunctional drug carrier for anticancer treatment, which combines chemotherapy and photothermal therapy. The rGO/MSN/PDA showed nearly twice the photothermal conversion efficiency of mesoporous silica-coated graphene oxide (GO/MSN) due to the reduction of GO and doping with PDA. In addition, the rGO/MSN/PDA showed pH-response DOX release abilities, which means higher release of DOX in tumor cells. The cell experiments in vitro proved that rGO/MSN/PDA with better biocompatibility compare to GO/MSN might offer a promising tool for improving the therapeutic effects of hepatocellular carcinoma cells through synergistic chemo-photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2024
·
IF 6.1
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 42
·6848-6857
·
IF 4.776
Ying Yang,Chen Wang,Chen Tian,Hailing Guo,Yuhua Shen,Manzhou Zhu
Considering traditional treatment methods, such as chemotherapy, with their potential side effects and lack of targeting, photodynamic therapy (PDT) and photothermal therapy (PTT), being innovative, with less side effects, and light-controlled strategies for antitumour applications, have received extensive attention, but the efficacy of PDT is seriously hindered by the hypoxia tumour microenvironment. Here, a multifunctional nanocomposite composed of an iron oxide (Fe3O4) core and two shells of manganese dioxide (MnO2) and polypyrrole (PPy) was successfully prepared and used to solve these issues. PPy, simultaneously as the photothermal agent and photosensitizer, was first combined with MnO2 to coat magnetic Fe3O4 for achieving an increase in the intracellular O2 concentration and to improve the generation ability of singlet oxygen upon laser irradiation, so that enhanced PDT/PTT could be obtained. After the efficient loading of doxorubicin (DOX) on the Fe3O4@MnO2@PPy nanocomposite, an acid controlled-release behaviour for DOX as well as magnetic-targeting-assisted synergistic effects of chemotherapy and improved PDT/PTT for tumour cells could be realized, which could also protect normal cells from damage. All these features may render our nanocomposite a promising platform to reverse hypoxia-triggered PDT resistance and chemotherapy-caused side effects in cancer therapy and other biomedical applications.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 8
·期 6
·1223-1234
·
IF 5.047
Huiru Li,Xinyue Zhang,Xilin Lin,Shuqiang Zhuang,Yan Wu,Zhong Liu,Jianhua Rong,Jianhao Zhao
Based on the concept of starving tumor therapy, in this study we put forward a new idea that the pH-sensitive Ca2+ delivery of calcium carbonate nanoparticles (CaCO3 NPs) induced blood coagulation of tumor vessels, and first explored the effect of CaCO3 NPs on the in vitro and in vivo blood coagulation by acid stimulus. CaCO3 NPs with a size of about 100 nm and a porous structure of several nanometers were synthesized in an emulsion system, which showed a high loading capacity (49%) of doxorubicin hydrochloride (DOX) with an encapsulation efficiency of 98% and a pH-sensitive drug delivery. The hemolysis test showed that CaCO3 NPs were blood compatible. The in vitro Ca2+ delivery and blood clotting tests indicated that CaCO3 NPs pH-sensitively released Ca2+, and caused rapid blood coagulation at pH 5.0 but no thrombus at pH 7.4. Confocal laser scanning microscopy showed that after uptake by MCF-7 or MDA-MB-231 breast cancer cells, CaCO3 NPs mainly distributed in endosomes/lysosomes within the initial 2 h and then decomposed by acid stimulus, leading to the intracellular delivery of Ca2+ that subsequently migrated outside the cells. CaCO3 NPs were nontoxic to NIH3T3 mouse fibroblasts, but highly toxic to both MCF-7 and MDA-MB-231 cells after loading DOX. After topical administration into the breast tumors of mice, CaCO3 NPs evoked significant thrombosis and hemorrhage of tumor vasculature by hematoxylin–eosin and Masson's trichrome staining. These results indicated that CaCO3 NPs could induce blood coagulation via acid stimulus, showing potential applications in blocking tumor vessels for starving tumor therapy.
研究领域:
纳米技术
·
癌症治疗
·
药学科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Ding Wang,Yaoqing Chu,Shuiping Liu,Lianjiang Tan
Vessel normalization has proved imperative in tumor growth inhibition. In this work, biopolymer-based hybrid nanospheres capable of normalizing blood vessels were designed to improve the therapeutic effect of chemotherapeutic drugs. Zn 0.4 Fe 2.6 O 4 nanoparticles (ZFO NPs) were synthesized, and were encapsulated in cross-inked chitosan (CS) along with a nitric oxide (NO) precursor, DETA NONOate, forming hybrid ZFO/NO@CS nanospheres highly stable in physiological environment. The structure, morphology and size of the nanospheres were characterized. The ZFO/NO@CS nanospheres could release NO under acidic conditions typical of intratumoral and intracellular environment. The results of related factors expression, wound healing and tube formation assays demonstrated that both the encapsulated ZFO NPs and the released NO were able to inhibit angiogenesis in tumors. The ZFO/NO@CS nanospheres enhanced the antitumor efficacy of the chemotherapeutic drug DOX by normalizing tumor vessels, as evidenced by in vivo experiments for CT26 tumor-bearing mice. By analyzing the contents of Fe in the tumor and different organs, the nanospheres were found to accumulate primarily at the tumor site. The blood analysis showed little side effect of the nanospheres. The ZFO/NO@CS nanospheres have great potential in improving tumor therapeutic effect when used in combination with chemotherapeutic drugs.
研究领域:
纳米技术
·
癌症研究
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2020
·Vol. 9
·期 14
·2000205
·
IF 7.367
Yuda Zhu,Nini Xin,Zi Qiao,Suping Chen,Lingwan Zeng,Yusheng Zhang,Dan Wei,Jing Sun,Hongsong Fan
Bioactive metal–organic frameworks (bio-MOFs) built from biofunctional metal ions and linkers show a new strategy to construct multifunctional theranostic platforms. Herein, a bio-MOF is synthetized via the self-assembling of Fe 3+ ions and doxorubicin hydrochloride (DOX) molecules. Then, through a stepwise assembly strategy, another bio-MOFs structure consisting of Gd 3+ ions and 1,3,5-benzenetricarboxylic acid (H 3 BTC) is wrapped on the surfaces of Fe-DOX nanoparticles, followed by adsorbing photosensitizer indocyanine green (ICG). Specifically, the Gd-MOF shell structure can not only act as a contrast agent for magnetic resonance imaging (MRI), but also provides protection for Fe-DOX cores, controlling the release of DOX. The photoacoustic and photothermal imaging (PAI and PTI) methods are successfully introduced to the platform by loading ICG, providing potential applications for multimodal biological imaging. The in vitro and in vivo outcomes indicate that the Fe-DOX@Gd-MOF-ICG nanoplatform exhibits outstanding synergistic antitumor performance via MR/PA/PT imaging guided chemotherapy, photothermal and photodynamic combination therapy. The work may encourage further exploration of bio-MOFs based multifunctional theranostic platforms for multimodal imaging guided compound antitumor therapy, which will open an avenue of MOFs toward biological applications.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·
IF 2.7
Xiaoyi Song,Fan Yang,Ruixuan Ji,Bin Yang,Yin Lv,Zhong Wei
Traditional chemotherapy faces challenges related to limited drug efficacy and adverse reactions. Intelligent nanocarrier drug delivery systems (INDDSs) promise improved treatment outcomes with reduced toxicity. However, several clinical challenges persist in achieving rapid drug release and real-time monitoring. Herein, a ROS-responsive amphiphilic copolymer was synthesized: polyethylene glycol (mPEG-TK-OH) with ROS-responsive thioketal (TK) as the macromolecular initiator, and enzymatic ring-opening polymerization of caprolactone was performed. Small molecules of tetraphenylethylene (TPE) with aggregation-induced emission (AIE) properties were added to the polymer's terminus to enable fluorescence imaging and the ROS-responsive amphiphilic copolymer mPEG-TK-PCL-TPE with AIE properties is formed and enhances drug release monitoring through fluorescence resonance energy transfer (FRET) between TPE and the hydrophobic anti-cancer drug DOX. Leveraging distinct ROS levels between tumor and normal cells, these ROS-responsive nanomicelles effectively respond to high intracellular redox-active species and release DOX. The mPEG-TK-PCL-TPE micelles displayed a suitable size, high drug loading, and excellent imaging quality. In vitro cell experiments confirmed their biocompatibility and efficacy in inhibiting 4T1 tumor cells. This ROS-responsive amphiphilic copolymer, incorporating the AIE structure, introduces new opportunities for cancer treatment, enabling real-time drug release tracking and improving therapeutic outcomes.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
Journal of Nanomaterials
·
2018
·
IF 2.207
Kun Wang,Shouju Wang,Kun Chen,Yijing Zhao,Xingqun Ma,Lin Wang
Anaplastic thyroid cancer (ATC) is highly aggressive and tends to develop drug resistance to standard chemotherapies. To overcome the drug resistance of ATC, we synthesized dopamine-melanin nanoparticles (MNPs) loaded with doxorubicin (Dox) molecules. The Dox-loaded MNPs (Dox-MNPs) developed exhibited increased cellular uptake and enhanced therapeutic efficacy in drug-resistant ATC cell line HTh74R, compared with free Dox. The native MNPs were found to have excellent biocompatibility, which suggests that Dox-MNPs may have potential in the treatment of ATC.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）