Co-reporter:Yongbo Yang, Li Lin, Lijia Jing, Xiuli Yue, and Zhifei Dai
ACS Applied Materials & Interfaces July 19, 2017 Volume 9(Issue 28) pp:23450-23450
Publication Date(Web):June 28, 2017
DOI:10.1021/acsami.7b05867
A bimodal contrast nanoagent was developed by chelating gadolinium ions to 2-[bis[2-[carboxymethyl-[2-oxo-2-(2-sulfanylethyl-amino)ethyl]amino]ethyl]amino]acetic acid (DTDTPA)-modified CuInS2/ZnS quantum dots (QDs). The longitudinal relaxivity (r1) of the resulted QDs@DTDTPA-Gd nanoparticles (NPs) was calculated to be 9.91 mM–1 s–1, which was 2.5 times as high as that of clinically approved Gd-DTPA (3.9 mM–1 s–1). In addition, the in vivo imaging experiments showed that QDs@DTDTPA-Gd NPs could enhance both near-infrared fluorescence and T1-weighted magnetic resonance (MR) imaging of tumor tissue through passive targeting accumulation. Moreover, the high colloidal and fluorescence stabilities and good biocompatibility indicate that QDs@DTDTPA-Gd NPs have a great potential for use as an efficient nanoagent to integrate the extremely high sensitivity of fluorescence imaging to the high resolution of MR imaging. Integration of bimodal detectability in the same agent of QDs@DTDTPA-Gd NPs can avoid extra stress on the blood clearance mechanisms as the administration of multiple dose of agents.Keywords: bimodal contrast agent; Gd(III) chelate; magnetic resonance imaging; near-Infrared fluorescence imaging; quantum dots;
Co-reporter:Xiaoyou Wang;Li Lin;Renfa Liu;Min Chen;Binlong Chen;Bo He;Bing He;Xiaolong Liang;Wenbing Dai;Hua Zhang;Xueqing Wang;Yiguang Wang;Qiang Zhang
Advanced Functional Materials 2017 Volume 27(Issue 31) pp:
Publication Date(Web):2017/08/01
DOI:10.1002/adfm.201700406
In an attempt to manipulate the biological features of nanomaterials via both anisotropic shape and ligand modification, four types of nanoparticulates with good morphological stability are designed and engineered, including hybrid nanospheres, nanodiscs, and nanodiscs with edge modification or plane modification of octa-arginine (R8) sequence. It is found that the R8 modification anisotropy can trigger huge differences in the endocytosis, intracellular trafficking, and even tissue penetration of nanoparticulates. From plane modification to edge modification of R8, the maximum increase in cell uptake is up to 17-fold, which is much more significant than shape anisotropy alone. On the other hand, six types of different cell lines are investigated to simulate biological microenvironment. It is demonstrated that the maximum difference in cell uptake among six cell lines is 12-fold. Three main driving forces are found to contribute to such bio–nano interactions. Based on the findings of this study, it seems possible to manipulate the biointeraction mode of nanomaterials and its output by regulating their anisotropy in both shape and ligand modification.
Co-reporter:Yunxue Xu;Xiaolong Liang;Pravin Bhattarai;Yang Sun;Yiming Zhou;Shumin Wang;Wen Chen;Huiyu Ge;Jinrui Wang;Ligang Cui
Advanced Functional Materials 2017 Volume 27(Issue 48) pp:
Publication Date(Web):2017/12/01
DOI:10.1002/adfm.201704096
AbstractNanoparticles (NPs)-based diagnosis and phototherapy are emerging as the cutting-edge technologies for detection and treatment of cancer but their applications are still limited since insufficient and heterogeneous NPs accumulation in cancer often causes recurrence. To overcome these limitations, multifunctional microbubbles (MBs) were constructed with 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindotricarbocyanine iodide (DiR) and porphyrin grafted lipid (PGL). Both DiR and PGL self-assembled as microbubbles, the as-designed PGL-DiR MBs possess remarkably high drug loading contents (5.8% PGL and 10.38% DiR) and stable co-delivery drug combinations. In vivo experiments showed PGL-DiR MBs could serve as an excellent ultrasound contrast agent to enhance ultrasound imaging greatly for identifying the location and size of the tumors. Upon exposure to ultrasound, in situ conversion of PGL-DiR MBs into nanoparticles resulted in a remarkable increase in fluorescence intensity (~5 folds) in tumor compared with PGL-DiR NPs, validating the enhanced tumor accumulation and cellular uptake of therapeutic agents. PGL-DiR MBs showed complete tumor ablation without recurrence in vivo, while PGL-DiR NPs showed only 72.6% tumor growth inhibition at the same dose. We believe that PGL-DiR MBs will soon reach their full potential as an important class of phototherapeutic formulations and will contribute to remarkable advances in cancer treatments.
Co-reporter:Li Lin, Xiaoyou Wang, Xiaoda Li, Yongbo Yang, Xiuli Yue, Qiang Zhang, and Zhifei Dai
Bioconjugate Chemistry 2017 Volume 28(Issue 1) pp:
Publication Date(Web):October 10, 2016
DOI:10.1021/acs.bioconjchem.6b00508
This article reports an effective method to regulate hydrophobic drug release rate from partially silica-coated bicellar nanodisc generated from proamphiphilic organoalkoxysilane and dihexanoylphosphatidylcholine by introducing different molar percentages of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG2000) into planar bilayers of hybrid bicelles. It was found that the drug release rate increased with increasing the molar percentages of DSPE-PEG2000, and 57.38%, 69.21%, 78.69%, 81.64%, and 82.23% of hydrophobic doxorubicin was released within 120 h from the nanodics incorporating with 0%, 2.5%, 5%, 10%, and 20% DSPE-PEG2000, respectively. Compared with the non-PEGylated nanodisc and free doxorubicin, the PEGylated nanodiscs showed good biocompatibility, high cellular uptake, and adhesion, as well as high local drug accumulation. In addition, both in vitro and in vivo results demonstrated significantly improved antitumor efficacy of the PEGylated nanodisc than its control groups. Thus, the PEGylated nanodisc with partial silica coating offers a facile and efficient strategy of drug delivery for chemotherapy with improved patient acceptance and compliance.
Co-reporter:Pravin Bhattarai
Advanced Healthcare Materials 2017 Volume 6(Issue 14) pp:
Publication Date(Web):2017/07/01
DOI:10.1002/adhm.201700262
Cyanine dyes are greatly accredited in the development of non-invasive therapy that can “see” and “treat” tumor cells via imaging, photothermal and photodynamic treatment. However, these dyes suffer from poor pharmacokinetics inducing severe toxicity to normal cells, insufficient accumulation in tumor regions and rapid photobleaching when delivered in free forms. Nanoparticles engineered to encapsulate these compounds and delivering them into tumor regions have increased rapidly, however, so far, these nanoparticles (NPs) have not proved to be so effective to circumvent existing challenges. Newly designed multifunctional smart nanocarriers that can improve phototherapeutic properties of these dyes, co-encapsulate multiple potent therapeutic compounds, and simultaneously overcome limitations related to tumor recurrence, metastases, limited intracellular uptake, and tumor hypoxia have potential to revolutionize modern paradigm of cancer therapy. Such cyanine based multifunctional nanocarriers integrating imaging and therapy in a single platform can effectively produce better clinical outcomes in cancer treatment. This review briefly summarizes recent advancements of cyanine nanoprobes that are currently used as imaging/phototherapeutic agents in unimodal/bimodal/trimodal cancer theranostics. Finally, we conclude this review by addressing challenges of pre-existing therapeutic systems and designs adopted to overcome them with a brief insight assimilating future perspective of emerging cyanine-based NPs in cancer theranostics.
Co-reporter:Yiming Zhou, Xiaolong Liang and Zhifei Dai
Nanoscale 2016 vol. 8(Issue 25) pp:12394-12405
Publication Date(Web):16 Dec 2015
DOI:10.1039/C5NR07849K
Porphyrins have been used as pioneering theranostic agents not only for the photodynamic therapy, sonodynamic therapy and radiotherapy of cancer, but also for diagnostic fluorescence imaging, magnetic resonance imaging and photoacoustic imaging. A variety of porphyrins have been developed but very few of them have actually been employed in clinical trials due to their poor selectivity to tumorous tissue and high accumulation rates in the skin. In addition, most porphyrin molecules are hydrophobic and form aggregates in aqueous media. Nevertheless, the use of nanoparticles as porphyrin carriers shows great promise to overcome these shortcomings. Encapsulating or attaching porphyrins to nanoparticles makes them more suitable for tissue delivery because we can create materials with a conveniently specific tissue lifetime, specific targeting, immune tolerance, and hydrophilicity as well as other characteristics through rational design. In addition, various functional components (e.g. for targeting, imaging or therapeutic functions) can be easily introduced into a single nanoparticle platform for cancer theranostics. This review presents the current state of knowledge on porphyrin-loaded nanoparticles for the interwined imaging and therapy of cancer. The future trends and limitations of prophyrin-loaded nanoparticles are also outlined.
Co-reporter:Li Lin, Xiaoyou Wang, Yanyu Guo, Kuan Ren, Xiaoda Li, Lijia Jing, Xiuli Yue, Qiang Zhang and Zhifei Dai
RSC Advances 2016 vol. 6(Issue 83) pp:79811-79821
Publication Date(Web):17 Aug 2016
DOI:10.1039/C6RA18112K
Hydrophobic doxorubicin was successfully loaded into hybrid discoid bicelles generated from proamphiphilic organoalkoxysilane and dihexanoyl phosphatidylcholine at the ratio of 7:2 by conventional Bangham method in combination with sol–gel reaction and self-assembly process. The drug-loaded hybrid bicelles with about 60 nm diameter and 6 nm thickness were found to exhibit pH-sensitive release behavior, good biocompatibility and remarkably high stability towards surfactant solubilization, long-term storage, and many factors susceptible to destabilize conventional phospholipid bicelles. The hybrid bicelles were proved to have higher cellular uptake via endocytosis and adhesion than spherical cerasomes. The endocytosis of hybrid bicelles was related to clathrin, macropinocytosis and was energy-dependent. Both in vitro and in vivo results showed that the drug loaded bicelles can effectively inhibit tumor growth. In other words, such hybrid bicelles can be employed as a novel promising nanocarrier for hydrophobic drugs.
Co-reporter:Yushen Jin, Xiaolong Liang, Yunkun An, and Zhifei Dai
Bioconjugate Chemistry 2016 Volume 27(Issue 12) pp:
Publication Date(Web):November 9, 2016
DOI:10.1021/acs.bioconjchem.6b00603
The microwave and temperature sensitive liposomes were fabricated successfully from 1,2-dipalmityol-sn-glycero-3-phosphocholine (DPPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000) with a molar ratio of 4:1:0.26 by co-encapsulating NaCl and doxorubicin (DOX) through the thin-film hydration method to externally manipulate drug release at a predetermined location in the body at a desired time in the right dosage for combination microwave hyperthermia and chemotherapy of cancer to afford a synergistic therapeutic effect. It was found that the confinement of the high concentration of NaCl ions inside the small size of the liposomes led to a more-rapid temperature elevation than the dissociative ions upon microwave treatment. More than 67.6% doxorubicin was released from the DOX and NaCl co-loaded liposomes (DOX&NaCl@liposomes) upon microwave irradiation for 2 min. After incubation with 2 mg/mL DOX&NaCl@liposomes for 4 h followed by treatment with microwave for 2 min, the inhibition rate of human breast cancer cell MDA-MB-231 was evaluated as 76.1%, much higher than that for NaCl@liposomes (29.8%) and DOX@liposomes (40.2%). The tumor growth inhibition was evaluated to be 73.4% after intravenous injection of DOX&NaCl@liposomes followed by microwave irradiation, much higher than that with only NaCl@liposomes (41.5%) or DOX@liposomes (45.5%) combined with microwave irradiation. Therefore, DOX&NaCl@liposomes could serve as a promising thermochemotherapy nanomedicine for cancer treatment because of its excellent microwave susceptible property and good biocompatibility.
Co-reporter:Zhifei Dai
Nanomedicine: Nanotechnology, Biology and Medicine 2016 Volume 12(Issue 2) pp:456-457
Publication Date(Web):February 2016
DOI:10.1016/j.nano.2015.12.029
Co-reporter:Xiaolong Liang;Yanyan Li;Xiaoda Li;Lijia Jing;Zijian Deng;Xiuli Yue;Changhui Li
Advanced Functional Materials 2015 Volume 25( Issue 9) pp:1451-1462
Publication Date(Web):
DOI:10.1002/adfm.201402338
Polypyrrole nanoparticles conjugating gadolinium chelates were successfully fabricated for dual-modal magnetic resonance imaging (MRI) and photoacoustic imaging guided photothermal therapy of cancer, from a mixture of pyrrole and pyrrole-1-propanoic acid through a facile one-step aqueous dispersion polymerization, followed by covalent attachment of gadolinium chelate, using polyethylene glycol as a linker. The obtained PEGylated polypyrrole nanoparticles conjugating gadolinium chelates (Gd-PEG-PPy NPs), sized around around 70 nm, exhibited a high T1 relaxivity coefficient of 10.61 L mm−1 s−1, more than twice as high as that of the relating free Gd3+ complex (4.2 L mm–1 s−1). After 24 h intravenous injection of Gd-PEG-PPy NPs, the tumor sites exhibited obvious enhancement in both T1-weighted MRI intensity and photoacoustic signal compared with that before injection, indicating the efficient accumulation of Gd-PEG-PPy NPs due to the introduction of the PEG layer onto the particle surface. In addition, tumor growth could be effectively inhibited after treatment with Gd-PEG-PPy NPs in combination with near-infrared laser irradiation. The passive targeting and high MRI/photoacoustic contrast capability of Gd-PEG-PPy NPs are quite favorable for precise cancer diagnosing and locating the tumor site to guide the external laser irradiation for photothermal ablation of tumors without damaging the surrounding healthy tissues. Therefore, Gd-PEG-PPy NPs may assist in better monitoring the therapeutic process, and contribute to developing more effective “personalized medicine,” showing great potential for cancer diagnosis and therapy.
Co-reporter:Lijia Jing, Jiyun Shi, Di Fan, Yaqian Li, Renfa Liu, Zhifei Dai, Fan Wang, and Jie Tian
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 39) pp:22095
Publication Date(Web):September 23, 2015
DOI:10.1021/acsami.5b07856
This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG2000-DOTA), followed by chelating radioisotope of 177Lu. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide 177Lu, enabling the ability of the 177Lu-labeled cerasomes for radionuclide cancer therapy and even the combined therapy.Keywords: cerasome; indocyanine green; multimodal imaging; nanotheranostics; photothermal therapy
Co-reporter:Xiaolong Liang, Jing Gao, Lingdong Jiang, Jianwen Luo, Lijia Jing, Xiaoda Li, Yushen Jin, and Zhifei Dai
ACS Nano 2015 Volume 9(Issue 2) pp:1280
Publication Date(Web):January 19, 2015
DOI:10.1021/nn507482w
The high intensity focused ultrasound (HIFU) and thermosensitive cerasomes (HTSCs) were successfully assembled by employing cerasome-forming lipid (CFL) in combination with the component lipids of conventional low temperature sensitive liposomes (LTSLs) including 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000) and 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (MSPC). The HTSCs showed spherical shape with a mean diameter around 200 nm, exhibiting good biocompatibility. Both hydrophilic and lipophilic drugs can be efficiently encapsulated into HTSCs. In addition, the release rate of HTSCs could be conveniently adjusted by varying the molar ratios of CFL to DPPC. The drug loaded HTSCs showed much longer blood circulation time (half-life >8.50 ± 1.49 h) than conventional LTSLs (0.92 ± 0.17 h). An in vitro study demonstrated that the drug loaded HTSCs are highly stable at 37 °C and show a burst release at 42 °C, providing a capability to act synergistically against tumors. We found that the HTSCs with a proportion of 43.25% of CFL could release more than 90% hydrophilic drugs in 1 min at an elevated temperature of 42 °C generated by HIFU exposure. After intravenous injection of doxorubicin (DOX) loaded HTSCs at 5 mg DOX/kg, followed by double HIFU sonication, the tumor growth of the adenocarcinoma (MDA-MB-231) bearing mice could be significantly inhibited. Therefore, the drug loaded HTSCs combined with HIFU hold great potential for efficient local chemotherapy of cancer due to the ability to deliver high concentration of chemotherapy drugs directly to the tumor, achieve maximum therapeutic efficacy and minimal side effects, and avoid the damage to the healthy tissues caused by systemic administration of drugs.Keywords: cerasomes; high intensity focused ultrasound; local chemotherapy; thermosensitive liposome; triggered drug release;
Co-reporter:Xiao-Da Li, Xiao-Long Liang, Xiu-Li Yue, Jin-Rui Wang, Chang-Hui Li, Zi-Jian Deng, Li-Jia Jing, Li Lin, En-Ze Qu, Shu-Min Wang, Chun-Long Wu, Hua-Xing Wu and Zhi-Fei Dai
Journal of Materials Chemistry A 2014 vol. 2(Issue 2) pp:217-223
Publication Date(Web):06 Nov 2013
DOI:10.1039/C3TB21281E
A novel multifunctional theranostic agent has been successfully fabricated by loading iron oxide nanoparticles into poly(lactic acid) (PLA) microcapsules followed by surface functionalization with graphene oxide. Both in vitro and in vivo experiments proved that the resulting microcapsules could serve as contrast agents to simultaneously enhance ultrasound, magnetic resonance and photoacoustic imaging. The composite microcapsules show good biocompatibility and rapid response to magnetic fields. Due to the strong absorption of the near-infrared light, the composite microcapsules could efficiently kill cancer cells upon NIR laser irradiation. In addition, it was found that such a photothermal effect could be obviously enhanced by applying an external magnetic field. In a nutshell, this multifunctional microcapsule can be developed as a promising platform that integrates multimodality imaging and therapy capabilities for effective cancer theranostics.
Co-reporter:Xiuli Yue, Zhifei Dai
Advances in Colloid and Interface Science 2014 Volume 207() pp:32-42
Publication Date(Web):May 2014
DOI:10.1016/j.cis.2013.11.014
Highlights
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Design and synthesis of cerasome-forming lipids.
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Fabrication, characterization, stability and biocompatibility of cerasomes.
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Cerasomes for drug and gene carriers. > Cerasomal porphyrin for photodynamic therapy of cancer.
Co-reporter:Caixin Guo, Yushen Jin, and Zhifei Dai
Bioconjugate Chemistry 2014 Volume 25(Issue 5) pp:840
Publication Date(Web):April 29, 2014
DOI:10.1021/bc500092h
Among all the imaging techniques, ultrasound imaging has a unique advantage due to its features of real-time, low cost, high safety, and portability. Ultrasound contrast agents (UCAs) have been widely used to enhance ultrasonic signals. One of the most exciting features of UCAs for use in biomedicine is the possibility of easily putting new combinations of functional molecules into microbubbles (MBs), which are the most routinely used UCAs. Various therapeutic agents and medical nanoparticles (quantum dots, gold, Fe3O4, etc.) can be loaded into ultrasound-responsive MBs. Hence, UCAs can be developed as multifunctional agents that integrate capabilities for early detection and diagnosis and for imaging guided therapy of various diseases. The current review will focus on such state-of-the-art UCA platforms that have been exploited for multimodal imaging and for imaging guided photothermal therapy.
Co-reporter:Yanyan Li, Shuquan Zheng, Xiaolong Liang, Yushen Jin, Yidi Wu, Huichen Bai, Renfa Liu, Zhifei Dai, Zicai Liang, and Tiejun Shi
Bioconjugate Chemistry 2014 Volume 25(Issue 11) pp:2055
Publication Date(Web):September 26, 2014
DOI:10.1021/bc500414e
The therapeutic application of small interfering RNA (siRNA) requires safe nanocarriers for specific and efficient delivery in vivo. Herein, PEGylated cationic cerasomes (PCCs) were fabricated by doping a cationic lipid with a hydroxyl group into nanohybrid cerasomes. Multiple properties of PCCs provide a solution to many of the limitations associated with current platforms for the delivery of siRNA. The polyorganosiloxane surface imparts PCCs with higher morphological stability than conventional liposomes. The PEGylation of the cationic cerasome could protect the cerasome nanoparticles from agglomeration and macrophage capture, reduce protein absorption, and consequently prolong the blood circulating time and enhance the siRNA delivery efficiency. In addition, incorporation of the lipid containing a hydroxyl group further facilitates endosome release. Moreover, PCCs were further used to transport siRNA into the cytosol primarily via endocytosis. When applied to systemic administration, PCCs have demonstrated effective delivery into the liver and preferential uptake by hepatocytes in mice, thereby leading to high siRNA gene-silencing activity. All these results show potential therapeutic applications of PCCs-mediated delivery of siRNA for liver diseases.
Co-reporter:Guanglei Fu, Wei Liu, Yanyan Li, Yushen Jin, Lingdong Jiang, Xiaolong Liang, Shanshan Feng, and Zhifei Dai
Bioconjugate Chemistry 2014 Volume 25(Issue 9) pp:1655
Publication Date(Web):August 9, 2014
DOI:10.1021/bc500279w
This paper reported a core–shell nanotheranostic agent by growing Prussian blue (PB) nanoshells of 3–6 nm around superparamagnetic Fe3O4 nanocores for targeted photothermal therapy of cancer under magnetic resonance imaging (MRI) guidance. Both in vitro and in vivo experiments proved that the Fe3O4@PB core–shell nanoparticles showed significant contrast enhancement for T2-weighted MRI with the relaxivity value of 58.9 mM–1·s–1. Simultaneously, the composite nanoparticles exhibited a high photothermal effect under irradiation of a near-infrared laser due to the strong absorption of PB nanoshells, which led to more than 80% death of HeLa cells with only 0.016 mg·mL–1 of the nanoparticles with the aid of the magnetic targeting effect. Using tumor-bearing nude mice as the model, the near-infrared laser light ablated the tumor effectively in the presence of the Fe3O4@PB nanoparticles and the tumor growth inhibition was evaluated to be 87.2%. Capabilities of MRI, magnetic targeting, and photothermal therapy were thus integrated into a single agent to allow efficient MRI-guided targeted photothermal therapy. Most importantly, both PB and Fe3O4 nanoparticles were already clinically approved drugs, so the Fe3O4@PB nanoparticles as a theranostic nanomedicine would be particularly promising for clinical applications in the human body due to the reliable biosafety.
Co-reporter:Yushen Jin, Yanyan Li, Hongjie Pan and Zhifei Dai
RSC Advances 2014 vol. 4(Issue 81) pp:42808-42815
Publication Date(Web):04 Sep 2014
DOI:10.1039/C4RA08515A
This study reported a facile fabrication of a reproducible and injectable cerasomal insulin formulation by encapsulating insulin into cerasomes via one-step construction. Notably, a wide range of the insulin release profiles was achieved by altering vesicle composition through incorporating the phospholipid of DPPC into cerasomes, and the mixed cerasomes showed excellent storage stability when the percentage content of DPPC was lower than 50%. It was found that the subcutaneous administration of the insulin-loaded cerasomes resulted in a reduction of blood glucose levels in a rat model of type I diabetes and the hypoglycemic effect was found to be composition dependent. The use of cerasomes significantly improved glucose tolerance from 6 hours (free insulin) to more than 16 hours (insulin-loaded cerasomes). Moreover, the insulin-loaded cerasomes displayed a prolonged and stable glucose-lowering profile over a period of over 12 hours compared with the insulin-loaded liposomes. These findings demonstrate that cerasomes have good potential for the use in an effective controlled release delivery system of insulin as well as other proteins with short half-life time.
Co-reporter:Yushen Jin, Yanyan Li, Xibo Ma, Zhengbao Zha, Liangliang Shi, Jie Tian, Zhifei Dai
Biomaterials 2014 35(22) pp: 5795-5804
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.03.086
Co-reporter:Xiaolong Liang, Xiaoda Li, Lijia Jing, Xiuli Yue, Zhifei Dai
Biomaterials 2014 35(24) pp: 6379-6388
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.04.094
Co-reporter:Zhengbao Zha, Jinrui Wang, Shuhai Zhang, Shumin Wang, Enze Qu, Youyi Zhang, Zhifei Dai
Biomaterials 2014 35(1) pp: 287-293
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.09.084
Co-reporter:Yan Ma;Xiaolong Liang;Sheng Tong;Gang Bao;Qiushi Ren
Advanced Functional Materials 2013 Volume 23( Issue 7) pp:815-822
Publication Date(Web):
DOI:10.1002/adfm.201201663
Abstract
A novel multifunctional drug-delivery platform is developed based on cholesteryl succinyl silane (CSS) nanomicelles loaded with doxorubicin, Fe3O4 magnetic nanoparticles, and gold nanoshells (CDF-Au-shell nanomicelles) to combine magnetic resonance (MR) imaging, magnetic-targeted drug delivery, light-triggered drug release, and photothermal therapy. The nanomicelles show improved drug-encapsulation efficiency and loading level, and a good response to magnetic fields, even after the formation of the gold nanoshell. An enhancement for T2-weighted MR imaging is observed for the CDF-Au-shell nanomicelles. These nanomicelles display surface plasmon absorbance in the near-infrared (NIR) region, thus exhibiting an NIR (808 nm)-induced temperature elevation and an NIR light-triggered and stepwise release behavior of doxorubicin due to the unique characteristics of the CSS nanomicelles. Photothermal cytotoxicity in vitro confirms that the CDF-Au-shell nanomicelles cause cell death through photothermal effects only under NIR laser irradiation. Cancer cells incubated with CDF-Au-shell nanomicelles show a significant decrease in cell viability only in the presence of both NIR irradiation and a magnetic field, which is attributed to the synergetic effects of the magnetic-field-guided drug delivery and the photothermal therapy. Therefore, such multicomponent nanomicelles can be developed as a smart and promising nanosystem that integrates multiple capabilities for effective cancer diagnosis and therapy.
Co-reporter:Zhengbao Zha, Zijian Deng, Yanyan Li, Changhui Li, Jinrui Wang, Shumin Wang, Enze Qu and Zhifei Dai
Nanoscale 2013 vol. 5(Issue 10) pp:4462-4467
Publication Date(Web):27 Mar 2013
DOI:10.1039/C3NR00627A
Photoacoustic tomography (PAT) has emerged as a hybrid, nonionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. Here, we demonstrate the application of a novel organic PAT contrast agent based on polypyrrole nanoparticles (PPy NPs). Monodisperse PPy NPs are ∼46 nm in diameter with strong absorption in the near-infrared (NIR) range, which allowed visualization of PPy NP-containing agar gel embedded in chicken breast muscle at a depth of ∼4.3 cm. Compared with PAT images based on the intrinsic optical contrast in mice, the PAT images acquired within 1 h after intravenous administration of PPy NPs showed the brain vasculature with greater clarity than hemoglobin in blood. Preliminary results showed no acute toxicity to the vital organs (heart, liver, spleen, lungs and kidneys) in mice following a single imaging dose of PPy NPs. Our results indicate that PPy NPs are promising contrast agents for PAT with good biocompatibility, high spatial resolution and enhanced sensitivity.
Co-reporter:Zhengbao Zha, Shumin Wang, Shuhai Zhang, Enze Qu, Hengte Ke, Jinrui Wang and Zhifei Dai
Nanoscale 2013 vol. 5(Issue 8) pp:3216-3219
Publication Date(Web):25 Feb 2013
DOI:10.1039/C3NR00541K
Novel “soft” microbubbles have been fabricated to show outstanding ultrasound imaging capability, and triggered CuS nanoparticles delivery through ultrasound-targeted microbubble destruction for efficient photothermal ablation of cancer cells.
Co-reporter:Shuhai Zhang, Zhengbao Zha, Xiuli Yue, Xiaolong Liang and Zhifei Dai
Chemical Communications 2013 vol. 49(Issue 60) pp:6776-6778
Publication Date(Web):07 Jun 2013
DOI:10.1039/C3CC43440K
The gadolinium chelate functionalized copper sulphide nanoparticles have been developed for simultaneous magnetic resonance imaging contrast enhancement and effective hyperthermal therapeutics.
Co-reporter:Zhengbao Zha, Shuhai Zhang, Zijian Deng, Yanyan Li, Changhui Li and Zhifei Dai
Chemical Communications 2013 vol. 49(Issue 33) pp:3455-3457
Publication Date(Web):08 Mar 2013
DOI:10.1039/C3CC40608C
Gelatin-stabilized copper sulphide nanoparticles with conjugated doxorubicin have been developed for combined photoacoustic imaging, enzyme-responsive drug release and photothermal therapy.
Co-reporter:Lijia Jing, Xiaolong Liang, Xiaoda Li, Yongbo Yang, Zhifei Dai
Acta Biomaterialia 2013 Volume 9(Issue 12) pp:9434-9441
Publication Date(Web):December 2013
DOI:10.1016/j.actbio.2013.08.018
Abstract
In this paper, theranostic nanoparticles (MnP-DOX NPs) were fabricated by conjugating Mn-porphyrin onto the surface of doxorubicin (DOX)-loaded poly(lactic acid) (PLA) nanoparticles (DOX NPs) for potential T1 magnetic resonance imaging and pH-sensitive drug delivery. An in vitro drug release study showed that the release rate of DOX from MnP-DOX NPs was slow at neutral pH but accelerated significantly in acidic conditions. It was found that MnP-DOX NPs could be easily internalized by HeLa cells and effectively suppressed the growth of HeLa cells and HT-29 cells due to the accelerated drug release in acidic lysosomal compartments. Magnetic resonance imaging (MRI) scanning analysis demonstrated that MnP-DOX NPs had much higher longitudinal relaxivity in water (r1 value of 27.8 mM−1 s−1 of Mn3+) than Mn-porphyrin (Mn(III)TPPS3NH2; r1 value of 6.70 mM−1 s−1 of Mn3+), behaving as an excellent contrast agent for T1-weighted MRI both in vitro and in vivo. In summary, such a smart and promising nanoplatform integrates multiple capabilities for effective cancer diagnosis and therapy.
Co-reporter:Dr. Xiaolong Liang;Xiaoda Li;Lijia Jing;Peng Xue;Lingdong Jiang; Qiushi Ren;Dr. Zhifei Dai
Chemistry - A European Journal 2013 Volume 19( Issue 47) pp:16113-16121
Publication Date(Web):
DOI:10.1002/chem.201302518
Abstract
This paper reports the facile design and synthesis of a series of lipidic organoalkoxysilanes with different numbers of triethoxysilane headgroups and hydrophobic alkyl chains linked by glycerol and pentaerythritol for the construction of cerasomes with regulated surface siloxane density and controlled release behavior. It was found that the number of triethoxysilane headgroups affected the properties of the cerasomes for encapsulation efficiency, drug loading capacity, and release behavior. For both water-soluble doxorubicin (DOX) and water-insoluble paclitaxel (PTX), the release rate from the cerasomes decreased as the number of triethoxysilane headgroups increased. The slower release rate from the cerasomes was attributed to the higher density of the siloxane network on the surface of the cerasomes, which blocks the drug release channels. In contrast to the release results with DOX, the introduction of one more hydrophobic alkyl chain into the cerasome-forming lipid resulted in a slower release rate of PTX from the cerasomes due to the formation of a more compact cerasome bilayer. An MTT viability assay showed that all of these drug-loaded cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning of the chemical structure of the cerasome-forming lipids would foster a new strategy to precisely regulate the release rate of drugs from cerasomes.
Co-reporter:Zhong Cao, Xiuli Yue, Xiaoda Li, and Zhifei Dai
Langmuir 2013 Volume 29(Issue 48) pp:14976-14983
Publication Date(Web):2017-2-22
DOI:10.1021/la401965a
Doxorubicin hydrochloride (DOX)-loaded magnetic cerasomes (DLMCs) were successfully constructed by loading both hydrophobic Fe3O4 nanoparticles (NPs) and antitumor drug DOX into the aqueous interior of cerasomes via facile one-step construction. A possible explanation is that the hydrophobic Fe3O4 NPs can be trapped inside the aqueous core of cerasomes through the formation of an intermediate Fe3O4/micelle complex. It was found that the loading content of Fe3O4 in DLMCs could reach the maximum at a Fe3O4/lipid molar ratio of 4:1. Moreover, DLMCs demonstrated high superparamagnetism and responded strongly to magnetic fields. In addition, DLMCs had a high encapsulation efficiency of 43.4 ± 4.7% and a high drug loading content of 3.2 ± 1.3%. In comparison to drug-loaded liposomes, DLMCs exhibited higher storage stability and better sustained release behavior. A cellular uptake study showed that the use of an external magnetic field enables a rapid and efficient uptake of DLMCs by cancer cells, resulting in higher capability to kill tumor cells than non-magnetic drug-loaded cerasomes. This study suggests that magnetic cerasome offers a potential and effective drug carrier for anticancer applications.
Co-reporter:Yushen Jin, Jinrui Wang, Hengte Ke, Shumin Wang, Zhifei Dai
Biomaterials 2013 34(20) pp: 4794-4802
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.03.027
Co-reporter:Yan Ma, Sheng Tong, Gang Bao, Chuang Gao, Zhifei Dai
Biomaterials 2013 34(31) pp: 7706-7714
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.07.007
Co-reporter:Yushen Jin, Xiuli Yue, Qingyuan Zhang, Xiaoyi Wu, Zhong Cao, Zhifei Dai
Acta Biomaterialia 2012 Volume 8(Issue 9) pp:3372-3380
Publication Date(Web):September 2012
DOI:10.1016/j.actbio.2012.05.022
Liposomal nanohybrid cerasomes display a remarkable ability to maintain their size and retain encapsulated doxorubicin (DOX) over a period of 90 days under storage conditions in solution compared with liposomes and liposils. Cerasomes retained 92.1 ± 2.9% of the drug payload after 90 days storage, much more than liposomes (35.2 ± 2.5%) and liposils (53.2 ± 5.5%). Under physiologically relevant conditions cerasomes exhibit a low initial burst in the first 5 h and subsequent sustained release of DOX over the next 150 h. Moreover, the magnitude of the initial burst and the rate of sustained release of DOX from cerasomes can be modulated by incorporating dipalmitoylphosphatidylglycerol (DPPG) in the cerasome structure and altering the ratios of the cerasome-forming lipid and phospholipids. Consequently, a wide range of release profiles can be achieved by altering the vesicle composition. Finally, human ovarian cancer cells are effectively killed by DOX released from cerasomes. Together these results suggest that cerasomes may be a promising drug delivery system for the long-term storage and controllable sustained release of the anticancer drug DOX.
Co-reporter:Zhong Cao, Xiuli Yue, Yushen Jin, Xiaoyi Wu, Zhifei Dai
Colloids and Surfaces B: Biointerfaces 2012 Volume 98() pp:97-104
Publication Date(Web):1 October 2012
DOI:10.1016/j.colsurfb.2012.05.001
Efforts to improve the stability of liposomes have recently led to the development of organic–inorganic liposomal cerasomes. In this study, we explore the potential to modulate the sustained release of paclitaxel from cerasomes by alteration in vesicle composition. Specifically, composite cerasomes have been prepared from mixtures of cerasome-forming lipid (lipid 1) and 1,2-distearoyl-sn-glycero-3-phosphocholine (lipid 2) via one-step construction. The influences of vesicle composition on the physical properties (e.g., particle diameter and surface charge density), physiochemical and long-term storage stability, drug-loading capacity, and release rates of paclitaxel have been investigated. Notably, a wide range of the release profiles of paclitaxel have been achieved by varying the contents of lipid 2, and the composite vesicles display excellent stability when the percentage content of lipid 2 is lower than 50%. Composite vesicles composed of lipids 1 and 2 at a 1:1 molar ratio also exhibited good cytocompatibility and the released paclitaxel effectively inhibit the proliferation of HeLa cancer cells. Together, the development of composite vesicles offers a promising strategy to obtain excellent stability, good drug-loading capacity and cytocompatibility, and enhanced paclitaxel release in single vesicles.Graphical abstractHighlights► Composite cerasomes (CCs) were constructed from mixtures of cerasome-forming lipid and DSPC lipid via one-step construction. ► The CCs displayed excellent stability when the percentage content of DSPC lipid was lower than 50%. ► Tuning the sustained release of paclitaxel achieved by varying the contents of DSPC lipid. ► The CCs offers a promising strategy to obtain excellent stability, cytocompatibility and tunable drug release in single vesicles.
Co-reporter:Guanglei Fu, Zhifei Dai
Talanta 2012 Volume 97() pp:438-444
Publication Date(Web):15 August 2012
DOI:10.1016/j.talanta.2012.04.059
Co-reporter:Shuhai Zhang, Zhengbao Zha, Xiuli Yue, Xiaolong Liang and Zhifei Dai
Chemical Communications 2013 - vol. 49(Issue 60) pp:NaN6778-6778
Publication Date(Web):2013/06/07
DOI:10.1039/C3CC43440K
The gadolinium chelate functionalized copper sulphide nanoparticles have been developed for simultaneous magnetic resonance imaging contrast enhancement and effective hyperthermal therapeutics.
Co-reporter:Xiao-Da Li, Xiao-Long Liang, Xiu-Li Yue, Jin-Rui Wang, Chang-Hui Li, Zi-Jian Deng, Li-Jia Jing, Li Lin, En-Ze Qu, Shu-Min Wang, Chun-Long Wu, Hua-Xing Wu and Zhi-Fei Dai
Journal of Materials Chemistry A 2014 - vol. 2(Issue 2) pp:NaN223-223
Publication Date(Web):2013/11/06
DOI:10.1039/C3TB21281E
A novel multifunctional theranostic agent has been successfully fabricated by loading iron oxide nanoparticles into poly(lactic acid) (PLA) microcapsules followed by surface functionalization with graphene oxide. Both in vitro and in vivo experiments proved that the resulting microcapsules could serve as contrast agents to simultaneously enhance ultrasound, magnetic resonance and photoacoustic imaging. The composite microcapsules show good biocompatibility and rapid response to magnetic fields. Due to the strong absorption of the near-infrared light, the composite microcapsules could efficiently kill cancer cells upon NIR laser irradiation. In addition, it was found that such a photothermal effect could be obviously enhanced by applying an external magnetic field. In a nutshell, this multifunctional microcapsule can be developed as a promising platform that integrates multimodality imaging and therapy capabilities for effective cancer theranostics.
Co-reporter:Zhengbao Zha, Shuhai Zhang, Zijian Deng, Yanyan Li, Changhui Li and Zhifei Dai
Chemical Communications 2013 - vol. 49(Issue 33) pp:NaN3457-3457
Publication Date(Web):2013/03/08
DOI:10.1039/C3CC40608C
Gelatin-stabilized copper sulphide nanoparticles with conjugated doxorubicin have been developed for combined photoacoustic imaging, enzyme-responsive drug release and photothermal therapy.
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