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Featured researches published by Qiao Jin.


ACS Nano | 2013

Mussel-Inspired Polydopamine: A Biocompatible and Ultrastable Coating for Nanoparticles in Vivo

Xiangsheng Liu; Jieming Cao; Huan Li; Jianyu Li; Qiao Jin; Ke-feng Ren; Jian Ji

Bioinspired polydopamine (PDA) has served as a universal coating to nanoparticles (NPs) for various biomedical applications. However, one remaining critical question is whether the PDA shell on NPs is stable in vivo. In this study, we modified gold nanoparticles (GNPs) with finely controlled PDA nanolayers to form uniform core/shell nanostructures (GNP@PDA). In vitro study showed that the PDA-coated GNPs had low cytotoxicity and could smoothly translocate to cancer cells. Transmission electron microscopy (TEM) analysis demonstrated that the PDA nanoshells were intact within cells after 24 h incubation. Notably, we found the GNP@PDA could partially escape from the endosomes/lysosomes to cytosol and locate close to the nucleus. Furthermore, we observed that the PDA-coated NPs have very different uptake behavior in two important organs of the liver and spleen: GNP@PDA in the liver were mainly uptaken by the Kupffer cells, while the GNP@PDA in the spleen were uptaken by a variety of cells. Importantly, we proved the PDA nanoshells were stable within cells of the liver and spleen for at least six weeks, and GNP@PDA did not show notable histological toxicity to main organs of mice in a long time. These results provided the direct evidence to support that the PDA surface modification can serve as an effective strategy to form ultrastable coatings on NPs in vivo, which can improve the intracellular delivery capacity and biocompatibility of NPs for biomedical application.


Langmuir | 2013

Surface and Size Effects on Cell Interaction of Gold Nanoparticles with Both Phagocytic and Nonphagocytic Cells

Xiangsheng Liu; Nan Huang; Huan Li; Qiao Jin; Jian Ji

With the development of nanotechnology and its application in biomedicine, studies on the interaction between nanoparticles and cells have become increasingly important. To understand the surface and size effects on cell interaction of nanoparticles, the cellular uptake behaviors of two series of gold nanoparticles (AuNPs) with both positively and negatively charged surfaces and sizes range from ~16 to ~58 nm were investigated in both phagocytic RAW 264.7 and nonphagocytic HepG2 cells. The internalization of AuNPs was quantified by ICP-MS, and the intracellular fate of NPs was evaluated by TEM analysis. The results showed that the AuNPs with positive surface charge have much higher cell internalization ability than those with negative surface charge in nonphagocytic HepG2 cells. However, the uptake extent of negatively charged AuNPs was similar with that of the positively charged AuNPs when in phagocytic RAW 264.7 cells. Among the tested size range, negatively charged AuNPs with a diameter of ~40 nm had the highest uptake in both cells, while the positively charged AuNPs did not show a certain tendency. Intracellular TEM analysis demonstrated the different fate of AuNPs in different cells, where both the positively and negatively charged AuNPs were mainly trapped in the lysosomes in HepG2 cells, but many of them were localized in phagosomes when in RAW 264.7 cells. Cytotoxicity of these AuNPs was tested by both MTT and LDH assays, which suggested NPs toxicity is closely related to the tested cell types besides the surface and size of NPs. It demonstrates that cell interaction between nanoparticles and cells is not only affected by surface and size factors but also strongly depends on cell types.


Biomacromolecules | 2011

Biocompatible Drug Delivery System for Photo-Triggered Controlled Release of 5-Fluorouracil

Qiao Jin; Fabian Mitschang; Seema Agarwal

The synthesis of a photo-triggered biocompatible drug delivery system on the basis of coumarin-functionalized block copolymers is reported. The coumarin-functionalized block copolymers poly(ethylene oxide)-b-poly(n-butyl methacrylate-co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin)) (PEO-b-P(BMA- co-CMA)) were synthesized via atom transfer radical polymerization (ATRP). The micelle-drug conjugates were made by covalent bonding of anticancer drug 5-fluorouracil (5-FU) to the coumarin under UV irradiation at wavelength >310 nm. These micelle-drug conjugates possessed spherical morphology with diameters of 70 nm from TEM images. In vitro drug release experiments showed the controlled release of anticancer drug 5-FU from the micelle-drug conjugates under UV irradiation (254 nm). These micelle-drug conjugates also showed excellent biocompatibility by the in vitro cytotoxicity experiments. The results suggest that these micelle-drug conjugates could be a promising candidate for the delivery of anticancer agents with low side effects on normal cells and excellent therapeutic efficacy to cancer cells.


Soft Matter | 2011

Biocompatible vesicles based on PEO-b-PMPC/α-cyclodextrin inclusion complexes for drug delivery

Gongyan Liu; Qiao Jin; Xiangsheng Liu; Li-Ping Lv; Chaojian Chen; Jian Ji

Poly(ethylene oxide) (PEO) and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) are biocompatible polymers that have delivered clinically proven benefits in various biomedical applications. Biocompatible polymer vesicles were prepared on basis of the inclusion complexation between α-cyclodextrins (α-CDs) and double-hydrophilic poly(ethylene oxide)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PEO-b-PMPC) in aqueous media without using organic solvent. The supramolecular structure of the nano-sized vesicles was demonstrated by transmission electron microscopy (TEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). The biocompatibility of PEO-b-PMPC block copolymers and PEO-b-PMPC/α-CDs vesicles were studied by cell viability test, and the results revealed that both of them showed excellent cytocompatibility. Hydrophilic doxorubicin (DOX·HCl) was successfully loaded into the vesicle with loading content of 10.3% and loading efficiency of 30%. The DOX·HCl loaded vesicles showed lower cytotoxicity than free drugs, and could efficiently deliver and release the drug into HepG2 cells as confirmed by fluorescence microscope (FM). With these properties, the polymer vesicles are attractive as drug carriers for pharmaceutical applications.


Soft Matter | 2010

Photo-responsive supramolecular self-assembly and disassembly of an azobenzene-containing block copolymer

Qiao Jin; Gongyan Liu; Xiangsheng Liu; Jian Ji

An azobenzene-containing block copolymer poly(ethylene oxide)-b-poly(6-[4-phenylazo phenoxy]hexyl methacrylate-co-2-(dimethylamino)ethyl methacrylate) (PEO-b-P(AzoMA-co-DMAEMA)) was successfully designed to explore self-assembly behavior in an aqueous solution. PEO-b-P(AzoMA-co-DMAEMA) can self-assemble into vesicles in water. The morphologies and sizes of the vesicles can be controlled by copolymerization of hydrophobic AzoMA with different amounts of DMAEMA. Spherical vesicle-to-compound vesicle-to-irregular vesicle transitions were observed by facilely adjusting the content of DMAEMA and AzoMA. After the addition of different amounts of β-CD, vesicles were transformed into micelles and at last dissociated. Alternating irradiation of the solution with UV and visible light induced the reversible supramolecular self-assembly and disassembly of vesicles because of the photo-induced trans-to-cis isomerization of azobenzene units. The supramolecular self-assembly and disassembly procedure was studied by dynamic light scattering (DLS), transmission electron microscopy (TEM) and UV-vis spectra.


ACS Applied Materials & Interfaces | 2014

Multidentate Polyethylene Glycol Modified Gold Nanorods for in Vivo Near-Infrared Photothermal Cancer Therapy

Xiangsheng Liu; Nan Huang; Huan Li; Haibo Wang; Qiao Jin; Jian Ji

Gold nanorods (AuNRs), because of their strong absorption of near-infrared (NIR) light, are very suitable for in vivo photothermal therapy of cancer. However, appropriate surface modification must be performed on AuNRs before their in vivo application because of the high toxicity of their original stabilizer cetyltrimethylammonium bromide. Multidentate ligands have attracted a lot of attention for modification of inorganic nanoparticles (NPs) because of their high ligand affinity and multifunctionality, while the therapeutic effect of multidentate ligands modified NPs in vivo remains unexplored. Here, we modified AuNRs with a polythiol PEG-based copolymer. The multidentate PEG coated AuNRs (AuNR-PTPEGm950) showed good stabilities in high saline condition and wide pH range. And they had much stronger resistance to ligand competition of dithiothreitol (DTT) than AuNRs coated by monothiol-anchored PEG. The AuNR-PTPEGm950 had very low cytotoxicity and showed high efficacy for the ablation of cancer cells in vitro. Moreover, the AuNR-PTPEGm950 showed good stability in serum, and they had a long circulation time in blood that led to a high accumulation in tumors after intravenous injection. In vivo photothermal therapy showed that tumors were completely cured without reoccurrence by one-time irradiation of NIR laser after a single injection of these multidentate PEG modified AuNRs.


Nanoscale | 2013

Multidentate zwitterionic chitosan oligosaccharide modified gold nanoparticles: stability, biocompatibility and cell interactions

Xiangsheng Liu; Haoyuan Huang; Gongyan Liu; Wenbo Zhou; Yangjun Chen; Qiao Jin; Jian Ji

Surface engineering of nanoparticles plays an essential role in their colloidal stability, biocompatibility and interaction with biosystems. In this study, a novel multidentate zwitterionic biopolymer derivative is obtained from conjugating dithiolane lipoic acid and zwitterionic acryloyloxyethyl phosphorylcholine to the chitosan oligosaccharide backbone. Gold nanoparticles (AuNPs) modified by this polymer exhibit remarkable colloidal stabilities under extreme conditions including high salt conditions, wide pH range and serum or plasma containing media. The AuNPs also show strong resistance to competition from dithiothreitol (as high as 1.5 M). Moreover, the modified AuNPs demonstrate low cytotoxicity investigated by both MTT and LDH assays, and good hemocompatibility evaluated by hemolysis of human red blood cells. In addition, the intracellular fate of AuNPs was investigated by ICP-MS and TEM. It showed that the AuNPs are uptaken by cells in a concentration dependent manner, and they can escape from endosomes/lysosomes to cytosol and tend to accumulate around the nucleus after 24 h incubation but few of them are excreted out of the cells. Gold nanorods are also stabilized by this ligand, which demonstrates robust dispersion stability and excellent hemocompatibility. This kind of multidentate zwitterionic chitosan derivative could be widely used for stabilizing other inorganic nanoparticles, which will greatly improve their performance in a variety of bio-related applications.


Colloids and Surfaces B: Biointerfaces | 2014

Zwitterionic drug nanocarriers: a biomimetic strategy for drug delivery.

Qiao Jin; Yangjun Chen; Yin Wang; Jian Ji

Nanomaterials self-assembled from amphiphilic functional copolymers have emerged as safe and efficient nanocarriers for delivery of therapeutics. Surface engineering of the nanocarriers is extremely important for the design of drug delivery systems. Bioinspired zwitterions are considered as novel nonfouling materials to construct biocompatible and bioinert nanocarriers. As an alternative to poly(ethylene glycol) (PEG), zwitterions exhibit some unique properties that PEG do not have. In this review, we highlight recent progress of the design of drug nanocarriers using a zwitterionic strategy. The possible mechanism of stealth properties of zwitterions was proposed. The advantages of zwitterionic drug nanocarriers deriving from phosphorylcholine (PC), carboxybetaine (CB), and sulfobetaine (SB) are also discussed.


Langmuir | 2011

Mixed Charged Zwitterionic Self-Assembled Monolayers as a Facile Way to Stabilize Large Gold Nanoparticles

Xiangsheng Liu; Haoyuan Huang; Qiao Jin; Jian Ji

Here we report a facile way of stabilizing large gold nanoparticles (AuNPs) by mixed charged zwitterionic self-assembled monolayers (SAMs). The citrate-capped AuNPs with diameters ranging from 16 nm to even ∼100 nm are well stabilized via a simple place exchange reaction with a 1:1 molar ratio mixture of negatively charged sodium 10-mercaptodecanesulfonic acid (HS-C10-S) and positively charged (10-mercaptodecyl)-trimethyl-ammonium bromide (HS-C10-N4). The 16 nm AuNPs protected by mixed charged zwitterionic SAMs not only show much better stability than the single negatively or positively charged AuNPs, but also exhibit exciting stability as well as those modified by monohydroxy (1-mercaptoundec-11-yl) tetraethylene glycol (HS-C11-EG4). Importantly, 16 nm AuNPs protected by mixed SAMs exhibit good stability in cell culture medium with 10% FBS and strong protein resistance, especially with excellent resistance against plasma adsorption. Moreover, the mixed charged zwitterionic SAMs are also able to well-stabilize larger AuNPs with a diameter of 50 nm, and to help remarkably improve their stability in saline solution compared with HS-C11-EG4 protected ones. When it comes to AuNPs with a diameter of 100 nm, the mixed charged zwitterionic SAM protected nanoparticles retain a smaller hydrodynamic diameter and even better long-term stability than those modified by mercaptopolyethylene glycol (M(w) = 2000, HS-PEG2000). The above results demonstrated that the mixed charged zwitterionic SAMs are able to have a similar effect on stabilizing the large gold nanoparticles just like the single-component zwitterionic SAMs. Concerning its ease of preparation, versatility, and excellent properties, the strategy based on the mixed charged zwitterionic SAM protection might provide a promising method to surface tailoring of nanoparticles for biomedical application.


Polymer Chemistry | 2013

Bioinspired phospholipid polymer prodrug as a pH-responsive drug delivery system for cancer therapy

Haibo Wang; Fangming Xu; Dandan Li; Xiangsheng Liu; Qiao Jin; Jian Ji

Efficient delivery systems should be stable in blood circulation, with efficient cellular uptake and rapid drug release in cancer cells. Herein, we synthesized P(2-(methacryloyloxy)-ethyl phosphorylcholine)-b-P(2-methoxy-2-oxoethyl methacrylate) via atom transfer radical polymerization. Doxorubicin (DOX) was linked to the polymer via a pH-responsive hydrazone bond. The polymer prodrug had high DOX content (10.6 wt%) and was able to self-assemble to form core–shell structured micelles. Dynamic light scattering showed that the average size of the micelles was 142.3 nm, which is the ideal size for the enhanced permeability and retention (EPR) effect. The shell of the micelles was composed of phosphorylcholine, which imitated the structure of cell membranes. Studies of intracellular uptake demonstrated that the prodrug micelles were internalized effectively by cancer cells. An in vitro release study indicated that the release of DOX at pH 5.0 was much faster than that at pH 7.4. Moreover, in vitro cytotoxicity showed that this polymer prodrug inhibited the growth of cancer cells remarkably, demonstrating its potential for use as an efficient drug delivery system.

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