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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Ultrasound-Triggered Phase-Transition Cationic Nanodroplets for Enhanced Gene Delivery

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.

CAS / MDL: 111-40-0 872-50-4
研究领域: 生物医学工程 · 基因治疗 · 材料科学
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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Facile preparation of fluorine-functionalized covalent organic frameworks@SiO2 as stationary phase for chromatographic separation of pharmaceutical molecules

Xuerui Zhang,Shuo Wang,Yixin Ren,Xiaoting Fu,Xiaodong Bi,Xia Wang,Ru-Song Zhao

Fluorine-functionalized covalent organic frameworks (F-COFs), owing to their multiple interactions such as F-F forces and hydrophobicity, have been widely used as candidate materials for stationary phases and other analytical purposes. How to incorporate F-COFs with a silica matrix (SiO 2 ) through a low-energy consumption method, and investigating the chromatographic properties for pharmaceutical targets, is of vital importance and requires significant further research. In this study, pentafluorophenyl (PFP) was used as a functional group to prepare PFP-COF@SiO 2 at room temperature through two distinct synthetic approaches. The resulting PFP-COF@SiO 2 materials, designated as I and II, were systematically characterized, and their chromatographic performances, influential factors, and retention mechanisms were investigated. These two COF materials demonstrated similar material properties and effective separation towards phenolic acids, alkaloids and antiviral drugs. The results indicated that the designed two synthetic routes were to some extent tolerable and compatible with the order of reagent addition. This work offers a novel method for preparing PFP-COF@SiO 2 stationary phases oriented for pharmaceutical chromatographic applications.

CAS / MDL: 1135-24-6
研究领域: 材料科学 · 分析化学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2025 · IF 2.8

Facile and green synthesis of PFP@SiO2 as stationary phase for liquid chromatography and its application for pharmaceutical analysis

Xuerui Zhang,Shuo Wang,Yixin Ren,Xiaoting Fu,Xiaodong Bi,Xia Wang,Ru-Song Zhao

The pentafluorophenyl (PFP)-functionalized stationary phases, due to their unique hydrophobicity and fluorophilic affinity, have received increasing attention in separation science. How to introduce PFP group effectively with a green chemistry approach has become an important issue. This work provided a facile and green synthetic route for preparing PFP@SiO 2 column. The liquid chromatography (LC) performance towards pharmaceutical molecules such as phenolic acids, flavonoids, and antiviral drugs was systematically explored. The results showed the PFP@SiO 2 column possessed a low back pressure and good solvent endurance (less affected by solvent effect). Under gradient elution mode, the column also showed a higher separation efficiency and good quantitative capacity towards complex natural product ( Sanguisorbae Radix Carbonisatum extract), which met the requirements of current standards and regulations. This work provides a facile green synthesis approach for preparing highly-performed PFP@SiO 2 column for pharmaceutical applications, and a powerful tool for biomedicine.

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Nature Communications · 2023 ·Vol. 14 ·期 1 ·1-12 · IF 16.6

Surface manipulation for prevention of migratory viscous crude oil fouling in superhydrophilic membranes

Zhao Yuanyuan,Yang Xiaobin,Cheng Zhongjun,Lau Cher Hon,Ma Jun,Shao Lu

Here, we present a proactive fouling prevention mechanism that endows superhydrophilic membranes with antifouling capability against migratory viscous crude oil fouling. By simulating the hierarchical architecture/chemical composition of a dahlia leaf, a membrane surface is decorated with wrinkled-pattern microparticles, exhibiting a unique proactive fouling prevention mechanism based on a synergistic hydration layer/steric hindrance. The density functional theory and physicochemical characterizations demonstrate that the main chains of the microparticles are bent towards Fe 3+ through coordination interactions to create nanoscale wrinkled patterns on smooth microparticle surfaces. Nanoscale wrinkled patterns reduce the surface roughness and increase the contact area between the membrane surface and water molecules, expanding the steric hindrance between the oil molecules and membrane surface. Molecular dynamic simulations reveal that the water-molecule densities and strengths of the hydrogen bonds are higher near the resultant membrane surface. With this concept, we can successfully inhibit the initial adhesion, migration, and deposition of oil, regardless of the viscosity, on the membrane surface and achieve migratory viscous crude oil antifouling. This research on the PFP mechanism opens pathways to realize superwettable materials for diverse applications in fields related to the environment, energy, health, and beyond.

研究领域: 环境科学 · 材料科学 · 能源技术
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TALANTA · 2019 · IF 4.916

Sensitive monitoring of RNA transcription by optical amplification of cationic conjugated polymers

Zengjin Li,Hui Guo,Fangyuan Xu,Wei Tang,Xinrui Duan

We reported a new strategy for sensitive monitoring in vitro RNA synthesis in real time based on fluorescence resonance energy transfer (FRET) from water-soluble conjugated polymer poly (9, 9-bis (6′-N, N, N,-trimethylammonium) hexyl) fluorene-co-alt-1,4-phenylene) bromide (PFP) to fluorogenic RNA aptamer/fluorophore (Spanich2/DFHBI and Broccoli/DFHBI) system. In this strategy, RNA of interest was transcribed accompanied by the Spanich2 or Broccoli. Then the 3, 5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI) bound to the RNA aptamer sequence and thereby induced a fluorescence signal. PFP was used as the fluorescence energy donor, and Spanich2/DFHBI was the fluorescence energy acceptor. The fluorescence signal of Spanich2/DFHBI was amplified by light-harvesting and fluorescence amplification ability of PFP via FRET. And the limit of detection (LOD) (0.29 nM) was near 10-fold lower than that of RNA aptamer/DFHBI (LOD is 2.8 nM) alone by measuring the FRET ratio, which greatly reduced the variation of background signals. Most importantly, the addition of PFP did not interfere with RNA transcription in vitro , so this method was successfully applied to sensitively monitor RNA transcription and effect of T7 RNA polymerase inhibitor in real time, supplying a sensitive and simple method to study the modulation and inhibitor of RNA polymerase in vitro .

CAS / MDL: 1643-19-2
研究领域: 生物化学 · 分子生物学 · 分析化学
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BIOMATERIALS · 2021 · IF 12.479

A versatile gas-generator promoting drug release and oxygen replenishment for amplifying photodynamic-chemotherapy synergetic anti-tumor effects

Xiudan Wang,Yuling Mao,Changshan Sun,Qinfu Zhao,Yikun Gao,Siling Wang

Excellent efficiency of combinational therapy of chemotherapy and photodynamic therapy (PDT) highly depends on the amounts of drug and oxygen in tumor tissue. However, how to cleverly promote drug release accompanied with improving oxygen concentration remains a challenge. Herein, we proposed a gas-generator that realized a high drug loading and integrated facilitation of drug release with oxygen replenishment into a single and simple system, utilizing huge cavities and mesoporous channels of hollow mesoporous silica nanoparticles (HMSNs) for encapsulating oxygen (O 2 ) saturated perfluoropentane (PFP) droplets, indocyanine green (ICG) and doxorubicin (DOX), biocompatible polydopamine (PDA) as the gatekeepers. Under irradiation of 808 nm laser , the thermal effect of PDA caused PFP droplets occur liquid-gas phase transition that triggered the burst release of DOX and O 2 , finally amplifying the synergetic effects of PDT and chemotherapy both in vitro and in vivo. The influence of PFP, GSH and laser on drug release kinetic was explored through mathematical models. Notably, the mechanism of gas-generator on accelerating drug release under irradiation based on doing volume work and enhancing diffusion coefficient was clarified by researching the relation between DOX release, PFP release and temperature change. Additionally, the way of replenishing O 2 did not rely on intracellular components but timely offered abundant “fuels” for producing reactive oxygen species (ROS) when compared with traditional manners. This work provides a new research strategy for boosting drug release and opens an avenue for constructing multifunctional controlled delivery systems.

研究领域: 癌症治疗 · 纳米医学 · 药物递送系统 · 光动力疗法 · 化疗
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Journal of Materials Chemistry B · 2020 ·Vol. 9 ·期 4 ·1151-1161 · IF 5.344

PSMA-targeted melanin-like nanoparticles as a multifunctional nanoplatform for prostate cancer theranostics

Liqun Dai,Guohua Shen,Yuanyuan Wang,Peng Yang,Hong Wang,Zhenhua Liu

Prostate-specific membrane antigen (PSMA) is highly expressed on the surface of most prostate tumor cells and is considered a promising target for prostate cancer imaging and treatment. It is possible to establish a PSMA-targeted theranostic probe to achieve early diagnosis and treatment of this cancer type. In this contribution, we prepared a multifunctional melanin-like polydopamine (PDA) nanocarrier decorated with a small-molecule PSMA inhibitor, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-l-lysine (DCL). PDA-DCL was then functionalized with perfluoropentane (PFP) and loaded with the photosensitizer chlorin e6 (Ce6) to give Ce6@PDA-DCL-PFP, which was successfully used for ultrasound-guided combined photodynamic/photothermal therapy (PDT/PTT) of prostate cancer. Compared with the corresponding non-targeted probe (Ce6@PDA-PEG-PFP), our targeted probe induced higher cellular uptake in vitro (6.5-fold) and more tumor accumulation in vivo (4.6-fold), suggesting strong active targeting capacity. Meanwhile, this new nanoplatform significantly enhanced the ultrasound contrast signal at the tumor site in vivo, thus facilitating precise and real-time detection of the tumor. In addition, this Ce6-loaded PDA nanoplatform produced a synergistic effect of PDT and PTT under 660 nm and 808 nm irradiation, inducing a more efficient killing effect compared with the individual therapy in vitro and in vivo. Furthermore, the tumor in the targeted group was more effectively suppressed than that in the non-targeted group under the same irradiation condition. This multifunctional probe may hold great potential for precise and early theranostics of prostate cancer.

研究领域: 癌症生物学 · 纳米技术 · 诊疗一体化 · 生物医学工程
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ACS Biomaterials Science & Engineering · 2019 · IF 4.511

Photothermal-Enhanced Phase-Transition Nanodroplets for Ultrasound-Mediated Diagnosis and Gene Transfection

Jinbiao Gao,Baiqing Yu,Chao Li,Wei Wang,Ming Xu,Zhong Cao,Xiaoyan Xie,Jie Liu

Gene therapy is one of the promising solutions in cancer therapeutics. Ultrasound-mediated gene delivery showed great potential as a noninvasive strategy for gene therapy. However, the efficiency of gene transfection and incorporation of multiple functions remain key challenges in the development of gene delivery systems. In this study, we developed perfluoropentane (PFP) and gold nanorods (AuNRs) loading nanodroplets for photothermal-enhanced ultrasound-mediated imaging and gene transfection. The nanodroplet theranostic system was formulated with fluorinated cationic poly(aspartamide) based polymer that encapsulated PFP, AuNRs, and plasmid DNA and was stabilized with a negatively charged poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) coating. The nanodroplets presented good stability, biocompatibility, and DNA binding stability. Upon treatment with both near-infrared and ultrasound energy, the photothermal and ultrasound-responsive system exerted a synergistic effect, in which strong adsorption of light induced hyperthermia that promoted the phase transition of PFP and the following ultrasound irradiation, generating strong acoustic cavitation and sonoporation, thus leading to enhanced ultrasound contrast imaging and gene transfection efficiency both in vitro and in vivo.

CAS / MDL: 111-40-0 872-50-4
研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 分子生物学 · 医学成像
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-11 · IF 10.6

Dual-mode nanoprobe strategy integrating ultrasound and near-infrared light for targeted and synergistic arterial thrombolysis

Wang Zhiwen,Jiang Nan,Jiang Zhixin,Wang Hao,Guo Yuxin,Zhong Fanglu,Gui Bin,Chen Yueying,Deng Qing,Zhou Qing,Hu Bo

Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis. Graphical Abstract

CAS / MDL: 25952-53-8 78-10-4
研究领域: 纳米技术 · 生物医学工程 · 诊疗学 · 心血管疾病
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