ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Di Gao,Ming Xu,Zhong Cao,Jinbiao Gao,Ya Chen,Yingqin Li,Zhe Yang,Xiaoyan Xie,Qing Jiang,Wei Wang,Jie Liu
Ultrasound as an external stimulus for enhanced gene transfection represents a safe, noninvasive, cost-effective delivery strategy for gene therapy. Herein, we have developed an ultrasound-triggered phase-transition cationic nanodroplet based on a novel perfluorinated amphiphilic poly(amino acid), which could simultaneously load perfluoropentane (PFP) and nucleic acids. The heptadecafluoroundecylamine (C11F17-NH2) was chosen to initiate β-benzyl-l-aspartate N-carboxyanhydride (BLA-NCA) ring-opening polymerization to prepare C11F17-poly(β-benzyl-l-aspartate) (C11F17-PBLA). Subsequently, C11F17-poly{N-[N′-(2-aminoethyl)]aspartamide} [C11F17-PAsp(DET)] was synthesized by aminolysis reaction of C11F17-PBLA with diethylenetriamine (DET). PFP/pDNA-loaded nanodroplets PFP-TNDs [PFP/C11F17-PAsp(DET)/LucDNA/γ-PGA or poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets] were primarily formulated by an oil/water emulsification method, followed by surface modification with PGA-g-mPEG. The average diameter of PFP-TNDs ranged from 300 to 400 nm, and transmission electron microscopy images showed that the nanodroplets were nearly spherical in shape. The ζ potential of the nanodroplets dramatically decreased from +54.3 to +15.3 mV after modification with PGA-g-mPEG, resulting in a significant increase of the stability of the nanodroplets in the serum-containing condition. With ultrasound irradiation, the gene transfection efficiency was enhanced 14-fold on HepG2 cells, and ultrasound-triggered phase-transition cationic nanodroplets also displayed a good ultrasound contrast effect. These results suggest that the PFP/DNA-loaded phase-transition cationic nanodroplets can be utilized as efficient theranostic agents for targeting gene delivery.
研究领域:
生物医学工程
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基因治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Huanling Guo,Ming Xu,Zhong Cao,Wei Li,Lida Chen,Xiaoyan Xie,Wei Wang,Jie Liu
Ultrasound-induced microbubble sonoporation has been shown to effectively improve drug/gene delivery efficiency by enhancing tissue and cell permeability. However, the microscale size and short duration of ultrasound contrast agents limit their accumulation in target areas. Here, a kind of ultrasound-triggered phase-transitioning and size-changing cationic nanodroplet, perfluoropentane/C9F17-PAsp(DET)/miR-122/poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets (PFP-TNDs/miR-122), was developed to deliver microRNA-122 (miR-122) for hepatocellular carcinoma (HCC) treatment. PFP served as an ultrasound-sensitive core for ultrasound-triggered phase transition and size change from the nanoscale to the microscale. Positively charged C9F17-PAsp(DET) ensured adequate miRNA loading. PGA-g-mPEG, which served as the shell of the nanodroplet, modified the nanodroplets, enhanced their stability in serum, and protected miR-122 from degradation in vivo. The results exhibited that PFP-TNDs/miR-122 has a nanosize diameter (362 ± 15 nm) and remained stable for 24 h. After treatment with PFP-TNDs/miR-122 combined with ultrasound irradiation, the miR-122 expression level was significantly increased by approximately 600-fold in HepG2 cells, 500-fold in SMMC-7721 cells, and 30-fold in human HCC xenografts. Moreover, PFP-TNDs/miR-122 combined with ultrasound radiation effectively suppressed the growth, migration, and invasion of HCC cells, and inhibited tumor proliferation in mice. This study revealed that the biodegradable PFP-TNDs is a promising therapeutic gene carrier with functions of gene protection and effective gene delivery for clinical applications. Furthermore, PFP-TNDs/miR-122 associated with ultrasound irradiation may pave a new way to improve the prognosis of patients with HCC.
研究领域:
医学
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生物技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 29
·5845-5853
·
IF 4.543
Ping Zhang,Yang Cao,Huali Chen,Bo Zhou,Wenjing Hu,Liangke Zhang
In this study, a multi-functional drug delivery system, which combines targeted tumor treatment with glycyrrhetinic acid-modified nanodroplets and ultrasound imaging with low-boiling-point phase-change perfluorocarbon, was proposed and validated. The obtained nanodroplets were spherical in shape with an average size of 324.8 ± 183.7 nm and a negative zeta-potential. Low-intensity focused ultrasound (LIFU) was introduced to perform targeted US imaging via acoustic droplet vaporization (ADV) both in vitro and in vivo. The in vitro cytotoxicity and cellular uptake studies conducted on HepG2 cells demonstrated that nanodroplets modified with glycyrrhetinic acid enhanced the selective delivery to cells expressing high levels of glycyrrhetinic acid receptors. Moreover, the glycyrrhetinic acid-modified nanodroplets showed significant antitumor efficacy in HepG2 cell-bearing mice with the assistance of both passive targeting via the EPR effects and active targeting ability of glycyrrhetinic acid. In conclusion, our fabricated multi-functional nanodroplets possess targeted antitumor activity and simultaneous US imaging, providing high potential for targeted tumor theranostics.
研究领域:
药剂学
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肿瘤学
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医学影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2021
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IF 6.4
Dui Qin,Lei Zhang,Hongrui Zhu,Junjie Chen,Daocheng Wu,Ayache Bouakaz,Mingxi Wan,Yi Feng
Background Photothermal therapy (PTT) has attracted considerable attention for cancer treatment as it is highly controllable and minimally invasive. Various multifunctional nanosystems have been fabricated in an “all-in-one” form to guide and enhance PTT by integrating imaging and therapeutic functions. However, the complex fabrication of nanosystems and their high cost limit its clinical translation.Materials and Methods Herein, a high efficient “one-for-all” nanodroplet with a simple composition but owning multiple capabilities was developed to achieve ultrasound (US) imaging-guided and cavitation-enhanced PTT. Perfluoropentane (PFP) nanodroplet with a polypyrrole (PPy) shell (PFP@PPy nanodroplet) was synthesized via ultrasonic emulsification and in situ oxidative polymerization. After characterization of the morphology, its photothermal effect, phase transition performance, as well as its capabilities of enhancing US imaging and acoustic cavitation were examined. Moreover, the antitumor efficacy of the combined therapy with PTT and acoustic cavitation via the PFP@PPy nanodroplets was studied both in vitro and in vivo.Results The nanodroplets exhibited good stability, high biocompatibility, broad optical absorption over the visible and near-infrared (NIR) range, excellent photothermal conversion with an efficiency of 60.1% and activatable liquid-gas phase transition performance. Upon NIR laser and US irradiation, the phase transition of PFP cores into microbubbles significantly enhanced US imaging and acoustic cavitation both in vitro and in vivo. More importantly, the acoustic cavitation enhanced significantly the antitumor efficacy of PTT as compared to PTT alone thanks to the cavitation-mediated cell destruction, which demonstrated a substantial increase in cell detachment, 81.1% cell death in vitro and 99.5% tumor inhibition in vivo.Conclusion The PFP@PPy nanodroplet as a “one-for-all” theranostic agent achieved highly efficient US imaging-guided and cavitation-enhanced cancer therapy, and has considerable potential to provide cancer theranostics in the future.
研究领域:
生物医学工程
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肿瘤学
·
纳米医学
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Bing Cao,Yingfei Ma,Jian Zhang,Yanan Wang,Yating Wen,Yun li,Ruixue Wang,Donghai Cao,Ruiping Zhang
Oral biofilm is the leading cause of dental caries, which is difficult to completely eradicate because of the complicated biofilm structure. What's more, the hypoxia environment of biofilm and low water-solubility of conventional photosensitizers severely restrict the therapeutic effect of photodynamic therapy (PDT) for biofilm. Although conventional photosensitizers could be loaded in nanocarriers, it has reduced PDT effect because of aggregation-caused quenching (ACQ) phenomenon. In this study, we fabricated an oxygen self-sufficient nanodroplet (PFC/TPA@FNDs), which was composed of fluorinated-polymer (FP), perfluorocarbons (PFC) and an aggregation-induced emission (AIE) photosensitizer (Triphenylamine, TPA), to eradicate oral bacterial biofilm and whiten tooth. Fluorinated-polymer was synthesized by polymerizing (Dimethylamino)ethyl methacrylate, fluorinated monomer and 1-nonanol monomer. The nanodroplets could be protonated and behave strong positive charge under bacterial biofilm acid environment promoting nanodroplets deeply penetrating biofilm. More importantly, the nanodroplets had extremely high PFC and oxygen loading efficacy because of the hydrophobic affinity between fluorinated-polymer and PFC to relieve the hypoxia environment and enhance PDT effect. Additionally, compared with conventional ACQ photosensitizers loaded system, PFC/TPA@FNDs could behave superior PDT effect to ablate oral bacterial biofilm under light irradiation due to the unique AIE effect. In vivo caries animal model proved the nanodroplets could reduce dental caries area without damaging tooth structure. Ex vivo tooth whitening assay also confirmed the nanodroplets had similar tooth whitening ability compared with commercial tooth whitener H 2 O 2 , while did not disrupt the surface microstructure of tooth. This oxygen self-sufficient nanodroplet provides an alternative visual angle for oral biofilm eradication in biomedicine.
研究领域:
医学
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材料科学
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牙科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2017
·
IF 2.466
Xiaolei Tang,Yuhao Cheng,Shiting Huang,Feng Zhi,Ahu Yuan,Yiqiao Hu,Jinhui Wu
The low oxygen concentration limits the therapeutic efficacy of photodynamic therapy in treating cancer cells in hypoxia, since the cytotoxic 1 O 2 can't be effectively generated in this condition. To overcome this, we load photosensitizer into perfluorocarbon nanodroplet, which has a high oxygen capacity to enrich O 2 for photodynamic consumption. Under the well-controlled hypoxic condition, we test its efficacy both in vitro and in vivo . This method can be successfully used for destroying cancer cells in hypoxic condition.
研究领域:
肿瘤学
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生物医学工程
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Jinbiao Gao,Baiqing Yu,Chao Li,Ming Xu,Zhong Cao,Xiaoyan Xie,Wei Wang,Jie Liu
Ultrasound-triggered delivery system is among the various multifunctional and stimuli-responsive strategies that hold great potential as a robust solution to the challenges of localized drug delivery and gene therapy. In this work, we developed an ultrasound-triggered delivery system PFP/C 9 F 17 -PAsp(DET)/CAD/PGA- g -mPEG nanodroplet, which combined ultrasound responsive phase-change contrast agent, acid-cleavable doxorubicin prodrug and cationic amphiphilic fluorinated polymer carrier, aiming to achieve both high imaging contrast and preferable ultrasound-triggered anti-cancer therapeutic effect. The optimized nanodroplets were characterized as monodispersed particles with a diameter of about 400 nm, slightly positive surface charge and high drug-loading efficiency. The functional augmenter PGA- g -mPEG provided the nanodroplets good sustainability, low cytotoxicity and good serum compatibility, as confirmed by stability and biocompatibility tests. In ultrasound imaging study, the nanodroplets produced significant contrast with ultrasound irradiation (3.5 MHz, MI = 0.08) at 37 ℃. Cell uptake and cytotoxicity studies in HepG2 and CT-26 cells showed the enhanced drug uptake and therapeutic effect with the combination of nanodroplets and ultrasound irradiation. These results suggest that the PFP/CAD-loaded phase change nano-emulsion can be utilized as an efficient theranostic agent for both ultrasound contrast imaging and drug delivery.
研究领域:
医学影像学
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药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Yang Gao,Qingming Ma,Jie Cao,Yingying Shi,Jiashan Wang,Haixia Ma,Yong Sun,Yang Song
The combination of ultrasound and chemotherapy has been proposed as a promising strategy to achieve a better anticancer therapeutic efficacy. Here we present a facile strategy to construct novel bifunctional nanodroplets as smart vehicles for ultrasound and pH responsive delivery of anticancer agents. PFH is used as core and chitosan/alginate complexes are used as the stable shells of the nanodroplets. The effects of alginate/chitosan ratio, and the amount of surfactant as well as PFH on the size, size distribution, and encapsulation efficiency of nanodroplets are systematically investigated with the optimized formulation identified. The release of the encapsulated doxorubicin hydrochloride can be triggered by changing the pH value of the surrounding environment and the exposure to ultrasound. The nanodroplets also show strong ultrasound contrast via droplet-to-bubble transition as demonstrated by B-mode ultrasound imaging. The hemolytic activity and cytotoxicity are further studied, revealing the biocompatibility of the nanodroplets. The in vivo antitumor results demonstrate that the prepared droplets show excellent antitumor therapeutic efficacy and outstanding tumor-targeting ability. The proposed alginate/chitosan stabilized PFH nanodroplets represent an important advance in fabricating multifunctional therapeutic materials with great promises in the applications of combined antitumor therapies.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Di Gao,Jinbiao Gao,Ming Xu,Zhong Cao,Luyao Zhou,Yingqin Li,Xiaoyan Xie,Qing Jiang,Wei Wang,Jie Liu
For successful gene therapy, it is imperative to accumulate therapeutic gene in tumor tissues followed by efficiently delivering gene into targeted cells. Ultrasound irradiation, as a noninvasive and cost-effective external stimulus, has been proved to be one of the most potential external-stimulating gene delivery strategies recently in further improving gene transfection. In this study, we developed tumor-targeting ultrasound-triggered phase-transition nanodroplets AHNP-PFP-TNDs comprising a perfluorinated poly(amino acid) C11F17–PAsp (DET) as a core for simultaneously loading perfluoropentane (PFP) and nucleic acids, and a polyanionic polymer PGA-g-PEG-AHNP as the shell for not only modifying the surface of nanodroplets but also introducing an anti-Her2/neu peptide (AHNP) aiming to targeted treatment of Her2-overexpressing breast cancer. The results showed the average diameter of AHNP-PFP-TNDs was below 400 nm, nearly spherical in shape. The modification of PGA-g-PEG-AHNP not only increased the serum stability of the nanodroplets but also improved the affinity between nanodroplets and Her2-overexpressing breast cells. Both intratumor and intravenous injection of AHNP-PFP-TNDs into nude mice bearing HGC-27 xenografts showed that the gene transfection efficiency and the ultrasound contrast effect were significantly enhanced after exposed to the ultrasound irradiation with optimized ultrasound parameters. Therefore, this targeting nanodroplets system could be served as a potential theranostic vector for tumor targeting ultrasound diagnosis and gene therapy.
研究领域:
医学影像学
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肿瘤学
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED PHYSICS LETTERS
·
2023
·Vol. 122
·期 12
·
IF 4
Huang Anqi,An Shizhe,Wang Yuebo,Feng Kangyi,Yu Haiyang,Chen Zhuonan,Wan Mingxi,Zong Yujin
Phase-change nanodroplets (PCNDs) have been used as controllable theranostic agents in diverse therapeutic and diagnostic scenarios over the years. However, there is still a pressing need to monitor the accurate distribution of non-flowing extravascular PCNDs by clinical ultrasound for further quantitative analysis. Here, we propose a spatiotemporally super-resolved ultrasound monitoring technique based on tuned post-activation dynamics of high-bulk-boiling-point PCNDs with customized perfluorocarbon cores. The underlying idea was to make the stochastic recondensation-induced contrast signal dominate the total post-activation signal, thus obtaining detectable and resolvable recondensation signals at physiological temperature. The recondensation signal was extracted by inter-frame subtraction and then processed by a deep learning-based detection algorithm tailored to the recondensation signal patterns. Experiments in tissue-mimicking phantoms demonstrate that co-restricting the concentration of PCNDs and the focus-wave activation pulse duration could help generate recondensation signals with ideal detectability and sparsity for accurate monitoring. Meanwhile, the quantitative analysis of the super-resolved results shows the spatiotemporal sensitivity of the proposed technique under varying concentrations and activation pulse durations, which was consistent with the patterns drawn from the total post-activation signal and existing theories on post-activation dynamics of PCNDs. This technique may be suitable for in-depth extravascular monitoring and dose analysis for PCNDs-involved therapies.
研究领域:
医学影像
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纳米医学
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超声技术
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yaotian Su,Jiawei Zhao,Wenwei Zhan,Haocheng Yuan,Lingyun Wu,Gang Sui,Hongtao Zhang
Graphene structures have never been found to play a role in accelerating fabrication of functional hydrogels. In this work, it is initially discovered that multifunctional hydrogels are fabricated via ultra-fast polymerization (∼minutes) by graphene oxide-adsorbed liquid metal nanodroplets (LMNPs@GO) vs. by conventional approaches (∼hours/days). LMNPs@GO are used to rapidly initiate and further cross-link polyacrylic acid (PAA) chains into a three-dimensional (3D) network without any extra molecular initiators, cross-linkers, heat source, and/or protective gas. The polymerization process with LMNPs@GO is extremely faster than that without GO involved (20 s vs. 4 h of prepolymer formation, and then 10 min vs. 3 days of crosslinking) for free radical polymerization of PAA hydrogels. The resulting hydrogel with 2 wt% reduced graphene oxide (rGO) exhibits 600% increase in tensile strength and 950% enhancement in conductivity, as well as excellent self-healing capabilities, in comparison with that of the pure PAA. The sensitivity studies show its great potential for the application of flexible sensors. Furthermore, the hydrogel possesses good dissolving properties, which is greatly beneficial for recyclability of the LM. This creative study not only broadens a novel application of graphene for making advanced multifunctional polymer materials, but also provides a brand-new route to realization of ultra-fast manufacturing technology that is significantly promising for industrial production in wearable devices.
研究领域:
材料科学
·
化学工程
·
生物医学工程
✓ 已验证
DOI
高影响因子
ELECTROCHIMICA ACTA
·
2022
·
IF 7.336
Yongtao You,Silan Bai,Yamin Ma,Cheng Liu,Lishi Wang
ABSTRACT Phenothiazine is an intermediate in the synthesis of drugs, and its derivatives, i.e., chlorpromazine (CPZ) and promethazine (PMZ), are both the major tranquilizers. Herein, a nanoscale soft sensor constructed utilizing the interface between two immiscible electrolyte solutions (ITIES) for CPZ and PMZ drugs was introduced. A nanopipette with a 60 nm diameter orifice was used to support the ITIES , and voltammetry and amperometry were used for the qualitative and quantitative determination of these two drugs crossing the liquid/liquid (L/L) interface. Half-wave potentials ( Δ w o φ 1 / 2 ) of 0.107 V and 0.092 V (vs. Δ w o φ 1 / 2 , T E A + ) for PMZ + and CPZ + transfer from water to 1,2-dichloroethane (DCE) were obtained, respectively. Subsequently, the kinetics and effective hydrophilicity of these two drugs were thoroughly investigated. Moreover, there were two calibration curves for the determination results between the current and the concentration range for CPZ + and PMZ + by cyclic voltammetry (the concentrations range from 0.1 to 10 mmol −1 ) and amperometry (the concentrations range from 0.02 to 10 mmol −1 ). Finally, the actual drug recovery for these two drugs ranged from 94.83% to 111.02%, which indicates the accuracy in actual medicine is good. The above work provides a soft nano-liquid/liquid interfacial sensor with applications in drugs, including kinetics studies and drug determination, and many applications in detecting pharmaceutical molecules, cellular secretion and other bioorganic compounds.
研究领域:
分析化学
·
药物化学
·
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）