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Dive into the research topics where Zhishen Ge is active.

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Featured researches published by Zhishen Ge.


Journal of the American Chemical Society | 2013

Polyprodrug Amphiphiles: Hierarchical Assemblies for Shape-Regulated Cellular Internalization, Trafficking, and Drug Delivery

Xianglong Hu; Jinming Hu; Jie Tian; Zhishen Ge; Guoying Zhang; Kaifu Luo; Shiyong Liu

Solution self-assembly of block copolymers (BCPs) typically generates spheres, rods, and vesicles. The reproducible bottom-up fabrication of stable planar nanostructures remains elusive due to their tendency to bend into closed bilayers. This morphological vacancy renders the study of shape effects on BCP nanocarrier-cell interactions incomplete. Furthermore, the fabrication of single BCP assemblies with built-in drug delivery functions and geometry-optimized performance remains a major challenge. We demonstrate that PEG-b-PCPTM polyprodrug amphiphiles, where PEG is poly(ethylene glycol) and PCPTM is polymerized block of reduction-cleavable camptothecin (CPT) prodrug monomer, with >50 wt % CPT loading content can self-assemble into four types of uniform nanostructures including spheres, large compound vesicles, smooth disks, and unprecedented staggered lamellae with spiked periphery. Staggered lamellae outperform the other three nanostructure types, exhibiting extended blood circulation duration, the fastest cellular uptake, and unique internalization pathways. We also explore shape-modulated CPT release kinetics, nanostructure degradation, and in vitro cytotoxicities. The controlled hierarchical organization of polyprodrug amphiphiles and shape-tunable biological performance opens up new horizons for exploring next-generation BCP-based drug delivery systems with improved efficacy.


Angewandte Chemie | 2009

Responsive Supramolecular Gels Constructed by Crown Ether Based Molecular Recognition

Zhishen Ge; Jinming Hu; Feihe Huang; Shiyong Liu

Responsive supramolecular gels were constructed from crown ether terminated four-arm star poly(epsilon-caprolactone) (PCL-DB24C8) and dibenzylammonium-terminated two-arm PCL-DBAS (see scheme), exploiting the formation of pseudorotaxane linkages between crown ether and ammonium moieties. The resultant supramolecular gels exhibit thermo- and pH-induced reversible gel-sol transition.


Macromolecular Rapid Communications | 2009

Supramolecular Self-Assembly of Nonlinear Amphiphilic and Double Hydrophilic Block Copolymers in Aqueous Solutions

Zhishen Ge; Shiyong Liu

Supramolecular self-assembly of block copolymers in aqueous solution has received ever-increasing interest over the past few decades due to diverse biological and technological applications in drug delivery, imaging, sensing and catalysis. In addition to relative block lengths, molecular weights and solution conditions, chain architectures of block copolymers can also dramatically affect their self-assembling properties in selective solvents. This feature article mainly focuses on recent developments in the field of supramolecular self-assembly of amphiphilic and double hydrophilic block copolymers (DHBCs) possessing nonlinear chain topologies, including miktoarm star polymers, dendritic-linear block copolymers, cyclic block copolymers and comb-shaped copolymer brushes.


Macromolecular Rapid Communications | 2011

Supramolecular thermoresponsive hyperbranched polymers constructed from poly(N-isopropylacrylamide) containing one adamantyl and two β-cyclodextrin terminal moieties.

Zhishen Ge; Hao Liu; Yanfeng Zhang; Shiyong Liu

Poly(N-isopropylacrylamide) (PNIPAM) oligomer containing one adamantyl (AD) and two β-cyclodextrin (β-CD) moieties at the chain terminals, AD-PNIPAM-(β-CD)(2), was synthesized by atom transfer radical polymerization (ATRP) and successive click reactions. In aqueous solution, AD-PNIPAM-(β-CD)(2) spontaneously forms supramolecular thermoresponsive hyperbranched polymers via molecular recognition between AD and β-CD moieties. To the best of our knowledge, this work represents the first report of the construction of supramolecular thermoresponsive hyperbranched polymers from well-defined polymeric AB(2) building units.


Chemical Communications | 2013

PEG-sheddable polyplex micelles as smart gene carriers based on MMP-cleavable peptide-linked block copolymers

Zhishen Ge; Shiyong Liu

A matrix metalloproteinase-cleavable peptide-linked block copolymer was fabricated and utilized to construct PEG-sheddable polyplex micelles as smart gene delivery vectors, which were demonstrated to exhibit higher cellular uptake, improved endosomal escape, and high-efficiency gene transfection in the presence of matrix metalloproteinase-2.


Soft Matter | 2009

Synthesis and supramolecular self-assembly of stimuli-responsive water-soluble Janus-type heteroarm star copolymers

Zhishen Ge; Jian Xu; Jinming Hu; Yanfeng Zhang; Shiyong Liu

We report on the synthesis and stimuli-responsive self-assembly of novel double hydrophilic Janus-type A7B14 heteroarm star copolymers with two types of water-soluble polymer arms emanating from the two opposing sides of the rigid toroidal β-CD core. Janus-type A7B14 star copolymers of N-isopropylacrylamide (NIPAM) and 2-(diethylamino)ethyl methacrylate (DEA), (PDEA)7-CD-(PNIPAM)14, were synthesized by coupling atom transfer radical polymerization (ATRP) and click chemistry techniques, starting from a well-defined β-CD derivative. At first, β-CD-(I)7 was obtained by reacting β-CD with I2 in the presence of PPh3 at 70 °C, which can selectively transform seven primary hydroxyl groups of β-CD into iodine moieties. After converting to β-CD-(N3)7viaazidation of β-CD-(I)7, the subsequent esterification reaction of β-CD-(N3)7 with 2-bromopropionic bromide afforded (N3)7-CD-(Br)14. The ATRP of NIPAM monomer in 2-propanol/DMF mixture at 25 °C using (N3)7-CD-(Br)14 as the multifunctional initiator led to azide-containing 14-arm star polymers, (N3)7-CD-(PNIPAM)14. Well-defined Janus-type double hydrophilic star copolymers were then prepared by the click reaction of (N3)7-CD-(PNIPAM)14 with an excess of monoalkynyl-terminated PDEA. Upon adjusting solution pH and temperatures, (PDEA30)7-CD-(PNIPAM25)14 can reversibly self-assemble into two distinct types of polymeric vesicles with “inverted” nanostructures in aqueous solution.


Chemical Communications | 2014

Dual pH-triggered multistage drug delivery systems based on host–guest interaction-associated polymeric nanogels

Minghui Zan; Shizhong Luo; Zhishen Ge

The polymeric nanogels were constructed via host-guest interactions for dual pH-triggered multistage drug delivery, which showed tumor acidity-triggered nanogel reorganization into smaller nanoparticles for deep tissue penetration, high-efficiency cellular uptake, and intracellular endo-lysosomal pH-responsive drug release.


Journal of Materials Chemistry | 2012

Mixed polymeric micelles as multifunctional scaffold for combined magnetic resonance imaging contrast enhancement and targeted chemotherapeutic drug delivery

Tao Liu; Yinfeng Qian; Xianglong Hu; Zhishen Ge; Shiyong Liu

We report on the utilization of mixed diblock copolymer micelles as an integrated multifunctional platform for the cancer cell-targeted delivery of chemotherapeutic drugs and magnetic resonance (MR) imaging contrast enhancement under in vitro and in vivo conditions. Two types of amphiphilic diblock copolymers, PCL-b-P(OEGMA-FA) and PCL-b-P(OEGMA-Gd), consisting of a hydrophobic poly(e-caprolactone) (PCL) block and a hydrophilic poly(oligo(ethylene glycol) monomethyl ether methacrylate) (POEGMA) block, covalently attached with folic acid (FA) and DOTA-Gd (Gd) moieties, respectively, were synthesized via the combination of atom transfer radical polymerization (ATRP), ring-opening polymerization (ROP), and “click” post-functionalization. Mixed micelles co-assembled from PCL-b-P(OEGMA-FA) and PCL-b-P(OEGMA-Gd) possess hydrophobic PCL cores for loading chemotherapeutic drugs and hydrophilic POEGMA outer coronas functionalized with FA and Gd complexes for synergistic functions of targeted delivery and MR imaging contrast enhancement. As-prepared nanosized mixed micelles are capable of physically encapsulating paclitaxel, a well-known hydrophobic anticancer drug, with a loading content of ∼5.0 w/w%, exhibiting controlled release of up to ∼60% loaded drugs over a duration of ∼130 h. In vitrocell viability assays revealed that drug-free mixed micelles are almost non-cytotoxic up to a concentration of 0.2 g L−1, whereas paclitaxel-loaded ones can effectively kill HeLa cells at the same concentration. In vitro MR imaging experiments indicated dramatically increased T1 relaxivity (26.29 s−1mM−1) for mixed micelles compared to that of small molecule counterpart, alkynyl-DOTA-Gd (3.12 s−1mM−1). Further in vivo MR imaging experiments in rabbits revealed considerably enhanced signal intensity, prominent positive contrast enhancement, improved accumulation and retention, and extended blood circulation duration for FA-labeled mixed micellar nanoparticles within the rabbit liver, as compared to those for FA-free mixed micelles and small molecule alkynyl-DOTA-Gd complex. These preliminary results indicate that the reported mixed micellar nanocarriers possess synergistically integrated functions of cancer-targeted drug delivery and controlled release, and MR imaging contrast enhancement, which augurs well for their potential application as a novel type of theranostic platform.


Polymer Chemistry | 2014

Redox-responsive core cross-linked micelles based on cypate and cisplatin prodrugs-conjugated block copolymers for synergistic photothermal–chemotherapy of cancer

Yu Han; Minghui Zan; Shizhong Luo; Zhishen Ge; Shiyong Liu

Responsive cross-linked block copolymer micelles which have emerged as promising drug delivery systems showed high stability and on-demand drug release. The combination therapy of cancer can be achieved via co-delivery of varying therapeutic molecules in one system. Here, we developed a redox-responsive core cross-linked (CCL) micelle conjugated with cypate and cisplatin prodrugs within the cores for synergistic photothermal and chemotherapy. The block copolymer, poly[(2-(2-methoxyethoxy)ethyl methacrylate)-co-(N-methacryloxy succinimide)]-block-poly(N-(2-hydroxypropyl) methacrylamide) (P(MEO2MA-co-MASI)-b-PHPMA), was synthesized via reversible addition–fragment chain transfer (RAFT) polymerization. After partial amidation reaction of succinimide with 3-azidopropylamine, the alkynyl-functionalized cypate and Pt(IV) complex were conjugated via click reaction. The CCL micelles were fabricated by core cross-linking at 37 °C in aqueous solution using cystamine as the cross-linker. P(Pt-Cy-MEO2MA)-b-PHPMA CCL micelles showed redox-responsive cross-linker cleavage and cisplatin drug release in the presence of reductants. The conjugated cypate moieties in the cores of CCL micelles resulted in photothermal temperature increase and reactive oxygen species (ROS) generation under 805 nm near infrared (NIR) laser irradiation. The cytotoxicity of CCL micelles was investigated with and without NIR irradiation. A significant synergistic effect of photothermal therapy and chemotherapy was demonstrated against cisplatin-resistant human lung cancer cells A549R under NIR irradiation.


Macromolecular Rapid Communications | 2015

A Near-Infrared Photothermal Effect-Responsive Drug Delivery System Based on Indocyanine Green and Doxorubicin-Loaded Polymeric Micelles Mediated by Reversible Diels-Alder Reaction

Hui Li; Wendong Ke; Zhishen Ge

Near-infrared light (NIR) possesses great advantages for light-responsive controllable drug release, such as deep tissue penetration and low damage to healthy tissues. Herein, a NIR-responsive drug delivery system is developed based on a NIR dye, indocyanine green (ICG), and anticancer drug, doxorubicin (DOX)-loaded thermoresponsive block copolymer micelles, in which the drug release can be controlled via NIR irradiation. First, block copolymers, poly(oligo(ethylene glycol) methacrylate)-block-poly(furfuryl methacrylate) (POEGMA-b-PFMA), are synthesized by sequential reversible addition-fragmentation chain-transfer (RAFT) polymerization, followed by modification with N-octyl maleimide through Diels-Alder (DA) reaction to produce POEGMA-b-POMFMA. The self-assembly of POEGMA-b-POMFMA by nano-precipitation in aqueous solution affords the polymeric micelles which are used to simultaneously encapsulate ICG and DOX. Upon irradiation by NIR light (805 nm), the loaded DOX is released rapidly from the micelles due to partial retro DA reaction and local temperature increase-induced faster drug diffusion by the photothermal effect. Cytotoxicity evaluation and intracellular distribution observation demonstrate significant synergistic effects of NIR-triggered drug release, photothermal, and chemotherapy toward cancer cells under NIR irradiation.

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Shiyong Liu

University of Science and Technology of China

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Wendong Ke

University of Science and Technology of China

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Zengshi Zha

University of Science and Technology of China

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Yuheng Wang

University of Science and Technology of China

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Wei Yin

University of Science and Technology of China

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Yu Han

University of Science and Technology of China

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Hewen Liu

University of Science and Technology of China

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Guoying Zhang

University of Science and Technology of China

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Hao Liu

University of Science and Technology of China

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