ACS Applied Materials & Interfaces
·
2014
·
IF 5.9
Chun-Yang Sun,Yin-Chu Ma,Zi-Yang Cao,Dong-Dong Li,Feng Fan,Jun-Xia Wang,Wei Tao,Xian-Zhu Yang
Recently, micelles, which are self-assembled by amphiphilic copolymers, have attracted tremendous attention as promising drug delivery systems for cancer treatment. Thus, the hydrophobic core of the micelles, which could efficiently encapsulate small molecular drug, will play a significant role for the anticancer efficiency. Unfortunately, the effect of hydrophobicity of micellar core on its anticancer efficiency was rarely reported. Herein, the amphiphilic diblock polymers of poly(ethylene glycol) and polyphosphoester with different side groups (butyl, hexyl, octyl) were synthesized to tune the hydrophobicity of the micellar core. We found that the in vitro cytotoxicity of the DOX-loaded micelles decreased with the increasing hydrophobicity of micellar core due to the drug release rate. However, following systemic delivery, the DOX-loaded micelles with the most hydrophobic core exhibited the most significant inhibition of tumor growth in a MDA-MB-231 tumor model, indicating the importance of hydrophobicity of core on the antitumor efficacy of drug delivery systems.
研究领域:
药学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
·
2020
·
IF 3.333
Shupeng Li,Wei Zhao,Na Liang,Yingxue Xu,Yoshiaki Kawashima,Shaoping Sun
The clinical application of paclitaxel (PTX) is limited due to its low solubility and severe side effects. In this study, an amphiphilic graft copolymer based on mPEG , deoxycholic acid and N -acetyl- L -cysteine modified hyaluronic acid (mPEG-HA(DCA)-NAC) was synthesized and used as a redox-sensitive nano-sized drug delivery system. The polymer was characterized by Fourier transform infrared (FT-IR) and Proton nuclear magnetic resonance ( 1 H NMR) analysis. As an amphiphilic polymer, mPEG-HA(DCA)-NAC could self-assemble into micelles in aqueous milieu and encapsulate PTX in the hydrophobic core with high drug loading of 15.6% and high encapsulation efficiency of 73.8%. The PTX-loaded micelles had an average size of 147 nm and zeta potential of −38.3 mV. Physicochemical properties of the micelles were measured by TEM and XRD analysis . XRD analysis confirmed the successful encapsulation of PTX in an amorphous state. In vitro drug release study demonstrated the redox-sensitivity of the micelles. In vitro and in vivo antitumor efficacy study indicated that the PTX-loaded mPEG-HA(DCA)-NAC micelles had excellent antitumor effect but with low toxicity to the body. It can be concluded that the mPEG-HA(DCA)-NAC micellar system represents a promising nanocarrier for delivery of PTX.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2017
·
IF 6.216
Ming Zhang,Jing Wang,Wentao Wang,Jun Zhang,Ninglin Zhou
Carbon dots could be extended in biological applications for drug delivery and photothermal therapeutics due to their ability to improving therapeutic effect and reducing side effects. Here, we use doxorubicin (DOX) as the model drug, the amino and carboxyl coated magnetofluorescent carbon quantum dots (GdN@CQDs) as a carrier, Genipin (GP) as cross-linking agent to design and prepare a multifunctional drug delivery system triggered by near-infrared (NIR) light and pH dual-stimuli. The cytotoxicity of the nanoparticles has been examined by MTT assay. The fluorescent GdN@CQDs/GP serves as both a controllable drug release gatekeeper and a fluorescent probe for the visualization of the drug delivery process. In vitro and in vivo experiments showed that this platform can deliver anti-cancer drugs to cells, releasing them intracellular upon NIR irradiation, and effectively eliminate tumors through chemo-photothermal synergistic therapeutic effect.
研究领域:
生物医学工程
·
纳米医学
·
药物递送系统
✓ 已验证
DOI
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 21
·12757-12770
·
IF 3.361
Man Li,Longbing Ling,Qing Xia,Xinsong Li
Micelles self-assembled from small amphiphilic molecules are unstable in biological fluids, and thus are poor drug carriers. In contrast, amphiphilic polymer micelles can encapsulate hydrophobic drugs in their core to greatly enhance their aqueous solubility and extend their retention time in blood circulation owing to their hydrophilic shell. However, the major disadvantages of conventional polymer micelles are the heterogeneity of the amphiphilic polymer structure and premature drug leakage. Thus, herein, to address these shortcomings, disulfide crosslinked micelles composed of a small amphiphilic molecule, di-lipoyl-glycerophosphorylcholine (di-LA-PC), were developed as redox-responsive drug carriers. Specifically, di-LA-PC was synthesized and self-assembled to form crosslinked micelles under catalysis by dithiothreitol. The disulfide crosslinked micelles maintained high stability in a simulated physiological environment, but rapidly disassembled under reductive conditions. Furthermore, paclitaxel (PTX), as a model drug, was encapsulated in the core of the crosslinked micelles with a high loading content of 8.13%. The in vitro release studies indicated that over 80% of PTX was released from the micelles in the reductive environment, whereas less than 20% PTX was released without reduction in the 68 h test. Benefiting from their nanoscale characteristics, the PTX-loaded micelles showed efficient cellular internalization and effectively induced the death of cancer cells, as revealed in the MTT, apoptosis and cell cycle tests. Moreover, pharmacokinetic studies demonstrated that the crosslinked micelles prolonged the circulation of the incorporated PTX in the bloodstream and increased its accumulation in the tumor tissue via the EPR effect. Finally, the PTX-loaded micelles displayed prominent in vivo anti-tumor activity in a 4T1 xenograft tumor model. In summary, the di-LA-PC crosslinked micelle platform possesses excellent stability, high loading capacity and reduction-responsive release profile, which may have applications in the delivery of PTX and other anti-cancer drugs.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2020
·
IF 2.22
Jiyang Liu,Na Liang,Shupeng Li,Yang Han,Pengfei Yan,Yoshiaki Kawashima,Fude Cui,Shaoping Sun
The clinical application of paclitaxel is limited due to its low solubility and severe side effects. A tumor-targeting and redox-sensitive paclitaxel-loaded micellar system could exhibit high drug solubility, excellent antitumor activity and low toxicity to normal tissues. An mPEG and hexadecanol-modified hyaluronic acid with disulfide bridges in the molecules (mPEG-S-S-HA-C16) was designed and synthesized. Using mPEG-S-S-HA-C16 as the carrier, the paclitaxel-loaded micelles were fabricated, and their physicochemical properties were studied deeply. Moreover, the antitumor evaluation of the paclitaxel-loaded micelles was conducted in vitro and in vivo. For the optimized paclitaxel-loaded mPEG-S-S-HA-C16 micelles, the average size and zeta potential were 168.6 nm and −38.2 mV, respectively. In vitro drug release study demonstrated the redox-sensitivity of the micelles that the encapsulated paclitaxel could be released rapidly in the presence of glutathione. MTT assay confirmed the low toxicity of the polymeric material itself and the excellent cytotoxicity of paclitaxel-loaded mPEG-S-S-HA-C16 micelles against MCF-7 cells. Moreover, the in vivo antitumor evaluation demonstrated the superior antitumor efficacy of the paclitaxel-loaded micelles. These results suggested that the paclitaxel-loaded mPEG-S-S-HA-C16 micelles held great promise for targeted delivery of paclitaxel.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Yue Yang,Kaiqing Yun,Yunjian Li,Ling Zhang,Wenxuan Zhao,Zhihong Zhu,Baocheng Tian,Fen Chen,Weisan Pan
Integration of multiple therapies into one nanoplatform holds great promise to overcome the shortcomings of traditional single-modal therapy and achieve favorable antitumor efficacy. Herein, we constructed a dual receptor-targeting nanomicelle system with GSH-responsive drug release for precise fluorescence imaging and superior chemo-phototherapy of cancer. The synthetic amphiphilic hyaluronic acid derivative (FHSV) could self-assemble into nanomicelles in aqueous media. Then, paclitaxel (PTX) and photosensitizer IR780 iodide (IR780) were co-loaded into the micelles by a simple dialysis method. The resulting IR780/PTX/FHSV micelles with a particle size of 150.2 ± 6.9 nm exhibited excellent stability, GSH-responsive drug release and good photothermal/photodynamic efficacy. Once accumulated at the tumor sites, IR780/PTX/FHSV micelles efficiently entered tumor cells through receptor-mediated endocytosis and then rapidly release PTX and IR780 under GSH-rich tumor microenvironment . Upon NIR laser irradiation, IR780 produced local hyperthermia and sufficient reactive oxygen species to promote tumor cells apoptosis and necrosis. The results of in vitro and in vivo experiments consistently demonstrated that compared with single chemotherapy and phototherapy, the chemo-phototherapy could more efficiently kill tumor cells by synergistic antitumor effect. Therefore, our study provides a novel and efficient approach for multimodal treatment of malignant tumor.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 48
·7859-7869
·
IF 4.872
Huiyun Wen,Haiqing Dong,Jie Liu,Aijun Shen,Yongyong Li,Donglu Shi
Intelligent nanoparticles are capable of prolonged blood circulation without leakage of the payload and fast drug release upon exposure to environmental stimuli, such as redox stimuli, and therefore are highly desirable for cancer therapy. In this study, polymeric micelles were designed and developed with a hydrophilic poly(ethylene glycol) (PEG) shell and a hydrophobic poly-L-phenylalanine (PPhe) core, linked by a redox cleavable bond, i.e. mPEG-SS-PPhe. The mPEG-SS-PPhe micelles were loaded with the anticancer drug doxorubicin (DOX) and shown an on-demand release profile in the presence of redox agents such as glutathione (GSH). Remarkably, the GSH-triggered micellar dissociation accelerated in vitro release of DOX 4.87 fold faster at 10 mM GSH than that without GSH at 12 h. An enhanced inhibitory effect of DOX-loaded mPEG-SS-PPhe micelles was achieved by improving the intracellular GSH levels. Confocal laser scanning microscopy and flow cytometric analyses of HeLa cells further confirmed that DOX accumulation was accelerated by elevating the extracellular GSH concentrations. In addition, mPEG-SS-PPhe micelles showed excellent biocompatibility on L929 and HeLa cell lines. These redox-sensitive polymeric micelles may provide more possibilities as promising carriers for on-demand drug release in a controlled manner.
研究领域:
纳米技术
·
药剂学
·
癌症治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 43
·7612-7619
·
IF 0
Ying Wang,Qiaojie Luo,Rui Sun,Guangyu Zha,Xiaodong Li,Zhiquan Shen,Weipu Zhu
We report a facile strategy to synthesize pH-sensitive amphiphilic oligo(ethylene glycol) (OEG)–doxorubicin (DOX) alternative conjugates. Poly[oligo(ethylene glycol) malicate] (POEGM) with numerous pendent hydroxyl groups was first synthesized by the direct polycondensation of oligo(ethylene glycol) (OEG) with malic acid under mild conditions. Then, benzaldehyde groups were introduced into the POEGM backbone via esterification between the pendant hydroxyl groups and 4-formylbenzoic acid. DOX moieties were finally attached to the polymeric backbone via benzoic imine linkages to obtain the OEG–DOX conjugates. Because of the high molecular weight and alternate architecture, this type of amphiphilic OEG–DOX alternative conjugates can form stable micelles in aqueous solution with a high DOX loading content (38.2 wt%) and low critical micelle concentrations (0.021 mg mL−1). Due to the pH-sensitive benzoic imine linkages between the DOX moieties and polymeric backbone, DOX could be rapidly released from the micelles at pH 5.8, whereas only a minimal amount of DOX was released at pH 7.4 under the same conditions. The cytotoxicity assay indicates that the OEG–DOX conjugates show cytotoxic effects to MCF-7 tumor cells, while the corresponding polymer material POEGM–CHO exhibits a great biocompatibility for MCF-7 tumor cells. These pH-sensitive and high drug loading nano-carriers based on the OEG–DOX alternative conjugates provide a promising platform for targeted cancer therapy.
研究领域:
药学
·
生物材料
·
肿瘤学
✓ 已验证
DOI
PubMed
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Yanmei Shi,Ronghua Tan,Chan Yu,Ying Wan
Image-guided chemo-photothermal therapy based on near-infrared (NIR) theranostic agents has found promising applications in treating tumors. In this multimodal treatment, it is of critical importance to image real-time distribution of photothermal agents in vivo and to monitor therapeutic outcomes for implementing personalized treatment. In this study, an optimally synthesized dextran-polylactide (DEX-PLA) copolymer was assembled with doxorubicin (DOX) and DiR, a kind of NIR dye, to construct desirable micelles ((DiR + DOX)/DEX-PLA) for performing image-guided chemo-photothermal therapy. These (DiR + DOX)/DEX-PLA micelles had good physical and photothermal stability in aqueous media and showed high photothermal efficiency in vivo. Based on the H22-tumor-bearing mouse model, (DiR + DOX)/DEX-PLA micelles were found to accumulate inside tumors sustainably and to emit strong fluorescence signals for more than three days. The (DiR + DOX)@DEX-PLA micelles together with NIR laser irradiation were able to highly inhibit tumor growth or even eradicate tumors with one injection and two dose-designated 5-minute laser irradiations at the tumor site during 14 days of treatment. Furthermore, they showed almost no impairment to the body of the treated mice. These (DiR + DOX)@DEX-PLA micelles have confirmative translational potential in clinical tumor therapy on account of their persistent image-guided capacity, high antitumor efficacy and good in vivo safety.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Journal of Materials Chemistry C
·
2013
·Vol. 1
·期 36
·5756-5764
·
IF 0
Lingzhi Zhang,Chengcheng Zhao,Jinping Zhou,Tetsuo Kondo
Amphiphilic cationic cellulose derivatives with different long alkyl chains as hydrophobic segments were synthesized. They can self-assemble into cationic micelles in distilled water. The structure and properties of the micelles were characterized by elemental analysis, FT-IR, 1H NMR, ζ-potential measurements, DLS, TEM, and fluorescence spectroscopy. The hydrophobic cores of the micelles were used to load a hydrophobic dye (4,7-bis[4-(1,2,2-triphenylvinyl)phenyl]benzo-2,1,3-thiadiazole, BTPETD) and exhibited a stable photoluminescence. The fluorescence emission can quantitatively and sensitively respond to 2,4-dinitrophenol (DNP) and picric acid (PA) due to the electron transfer between BTPETD and the explosives, and the limit of detection was 200 and 50 nM for DNP and PA, respectively. The novel hydrophobically modified cationic cellulose micelles have the potential to prepare feasible, sensitive and stable sensor systems for detecting explosives in aqueous solutions.
研究领域:
材料科学
·
分析化学
✓ 已验证
DOI
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2020
·
IF 2.734
Nan Zhang,Jing Zhang,Baocheng Tian,Keke Li,Baohuan Wu,Jingtian Han
CD44 play a pivotal role in tumor progression and metastasis. Targeting CD44 expressing cells using hyaluronic acid (HA) is a promising approach in the treatment of many types of tumors. Here, CD44-targeted conjugate was introduced by hyaluronic acid-deoxycholic acid (HA-DOCA) through the connection of the ester bond. Hydrophilic drug Gemcitabine (GEM) and hydrophobic DOCA are linked by the amide linkage. The DOCA-GEM was mixed with HA-DOCA to form mixed micelles (MMs) with low critical micelle concentration . Dynamic laser light scattering and transmission electron microscope measurements revealed that HA-DOCA/DOCA-GEM MMs displayed sphericity, with an average diameter of 149 ± 3 nm, and negative zeta potential . Hemolysis and cytotoxicity studies confirmed the safety of the HA-DOCA conjugate. The in vitro drug release was investigated, demonstrating that the intracellular-mimicking microenvironment could accelerated the GEM release of the HA-DOCA/DOCA-GEM MMs. The HA-DOCA/DOCA-GEM MMs showed higher cellular uptake efficiency by MCF-7 cells according to confocal laser scanning microscopy and flow cytometry, therefore achieving much stronger anticancer efficacy than free GEM and DOCA-GEM micelles. Our results suggest that HA-DOCA/DOCA-GEM MMs might be a potential candidate for cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Caiying Zhu,Jingjing Xiao,Ming Tang,Hua Feng,Wulian Chen,Ming Du
The preparation of polymer therapeutics capable of controlled release of multiple chemotherapeutic drugs has remained a tough problem in synergistic combination cancer therapy. Herein, a novel dual-drug co-delivery system carrying doxorubicin (DOX) and platinum(IV) (Pt[IV]) was developed. An amphiphilic diblock copolymer, PCL-b-P(OEGMA-co-AzPMA), was synthesized and used as a nanoscale drug carrier in which DOX and Pt(IV) could be packaged together. The copolymers were shell cross-linked by Pt(IV) prodrug via a click reaction. Studies on the in vitro drug release and cellular uptake of the dual-drug co-delivery system showed that the micelles were effectively taken up by the cells and simultaneously released drugs in the cells. Futhermore, the co-delivery polymer nanoparticles caused much higher cell death in HeLa and A357 tumor cells than either the free drugs or single-drug-loaded micelles at the same dosage, exhibiting a synergistic combination of DOX and Pt(IV). The results obtained with the shell cross-linked micelles based on an anticancer drug used as a cross-linking linkage suggested a promising application of the micelles for multidrug delivery in combination cancer therapy.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）