ORCID Profile
0000-0002-3189-2756
Current Organisation
The University of Edinburgh
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Publisher: American Chemical Society (ACS)
Date: 08-12-2022
Publisher: Public Library of Science (PLoS)
Date: 18-10-2010
Publisher: Springer Science and Business Media LLC
Date: 31-01-2023
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.JCONREL.2010.09.001
Abstract: HSV-2-gD2 DNA vaccine was precisely delivered to immunologically sensitive regions of the skin epithelia using dry-coated microprojection arrays. These arrays delivered a vaccine payload to the epidermis and the upper dermis of mouse skin. Immunomicroscopy results showed that, in 43 ± 5% of microprojection delivery sites, the DNA vaccine was delivered to contact with professional antigen presenting cells in the epidermal layer. Associated with this efficient delivery of the vaccine into the vicinity of the professional antigen presenting cells, we achieved superior antibody responses and statistically equal protection rate against an HSV-2 virus challenge, when compared with the mice immunized with intramuscular injection using needle and syringe, but with less than 1/10th of the delivered antigen.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.BIOMATERIALS.2012.11.035
Abstract: The recent emergence of micro-devices for vaccine delivery into upper layers of the skin holds potential for increased immune responses using physical means to target abundant immune cell populations. A challenge in doing this has been a limited understanding of the skin elastic properties at the micro scale (i.e. on the order of a cell diameter ~10 μm). Here, we quantify skin's elastic properties at a micro-scale by fabricating customised probes of scales from sub- to super-cellular (0.5 μm-20 μm radius). We then probe full thickness skin first with force-relaxation experiments and subsequently by elastic indentations. We find that skin's viscoelastic response is scale-independent: consistently a ~40% decrease in normalised force over the first second, followed by further 10% reduction over 10 s. Using Prony series and Hertzian contact analyses, we determined the strain-rate independent elastic moduli of the skin. A high scale dependency was found: the smallest probe encountered the highest elastic modulus (~30 MPa), whereas the 20 μm radius probe was lowest (below 1 MPa). We propose that this may be a result of the load distribution in skin facilitated by the hard corneocytes in the outermost skin layers, and softer living cell layers below.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC03731D
Abstract: By replacing Lewis acids with Brønsted acids as catalysts, continuous flow synthesis of hypercrosslinked polymers is achieved within 10% of the time required for a typical batch reaction. Compared with batch-synthesised polymers, the flow-produced materials take up 24% more CO2, precluding the need for lengthy reaction protocols to yield high-performance hypercrosslinked polymers for carbon capture.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9TB01154D
Abstract: Novel photoactive metal–organic framework nanoparticles were developed using a facile post-synthetic conjugation method to achieve tunable combinational PDT and PTT.
Publisher: Elsevier BV
Date: 2021
Publisher: American Chemical Society (ACS)
Date: 22-10-2018
DOI: 10.1021/ACS.NANOLETT.8B03043
Abstract: To make nanomedicine potentially applicable in a clinical setting, several methods have been developed to synthesize pure nanodrugs (PNDs) without using any additional inert carriers. In this work, we report a novel green, low-cost, and scalable ice-template-assisted approach which shows several unique characteristics. First, the whole process only requires adding a drug solution into an ice template and subsequent melting (or freeze-drying), allowing easy industrial mass production with low capital investment. Second, the production yield is much higher than that of the traditional reprecipitation approach. The yield of Curcumin (Cur) PNDs is over two orders (∼140 times) magnitude higher than that obtained in a typical reprecipitation preparation. By adjusting simple processing parameters, PNDs with different sizes (∼20-200 nm) can be controllably obtained. Finally, the present approach can be easily applicable for a wide range of hydrophobic therapeutic drugs without any structural modification.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.JCONREL.2012.01.030
Abstract: Many vaccines make use of an adjuvant to achieve stronger immune responses. Alternatively, potent immune responses have also been generated by replacing the standard needle and syringe (which places vaccine into muscle) with devices that deliver vaccine antigen to the skin's abundant immune cell population. However it is not known if the co-delivery of antigen plus adjuvant directly to thousands of skin immune cells generates a synergistic improvement of immune responses. In this paper, we investigate this idea, by testing if Nanopatch delivery of vaccine - both the antigen and the adjuvant - enhances immunogenicity, compared to intramuscular injection. As a test-case, we selected a commercial influenza vaccine as the antigen (Fluvax 2008®) and the saponin Quil-A as the adjuvant. We found, after vaccinating mice, that anti-influenza IgG antibody and haemagglutinin inhibition assay titre response induced by the Nanopatch (with delivered dose of 6.5ng of vaccine and 1.4μg of Quil-A) were equivalent to that of the conventional intramuscular injection using needle and syringe (6000ng of vaccine injected without adjuvant). Furthermore, a similar level of antigen dose sparing (up to 900 fold) - with equivalent haemagglutinin inhibition assay titre responses - was also achieved by delivering both antigen and adjuvant (1.4μg of Quil-A) to skin (using Nanopatches) instead of muscle (intramuscular injection). Collectively, the unprecedented 900 fold antigen dose sparing demonstrates the synergistic improvement to vaccines by co-delivery of both antigen and adjuvant directly to skin immune cells. Successfully extending these findings to humans with a practical delivery device - like the Nanopatch - could have a huge impact on improving vaccines.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.JCONREL.2009.06.029
Abstract: Dry-coated microprojections (MPs) deliver vaccine to abundant immunogenic cells within the skin to induce immune responses. Success in this targeted vaccine delivery relies on overcoming the challenges of dry-coating the vaccine onto the very small (<or=90 microm length) and densely packed (approximately 20,000 cm(-2)) MPs. In this paper, we show that a gas-jet drying coating method achieves the desired uniform coating. The coating approach is robustly demonstrated on compounds representative of a range of immunotherapeutics (e.g. DNA, proteins), with each uniformly coated on thousands of MPs. Furthermore, the dry-coating remains intact during skin insertion, and then releases within the wet skin cellular environment within 3 min. Finally, we applied ovalbumin protein coated MP patches to immunise mice, achieving comparable antibody levels (p=0.08) with needle and syringe intramuscular injection. In summary, this paper presents a simple, practical and versatile method to achieve uniform coating on very small and densely packed MPs for a needle-free and targeted vaccine delivery technology.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5NR04436G
Abstract: The core–shell nanoparticles are constructed by encapsulating the g-C 3 N 4 nanosheet into ZIF-8 shells for dual-color fluorescence imaging and combined photo-chemo therapy.
Publisher: Public Library of Science (PLoS)
Date: 21-04-2010
Publisher: Informa UK Limited
Date: 04-2012
DOI: 10.3109/17435390.2011.569092
Abstract: Systematic studies probing the effects of nanoparticle surface modification and formulation pH are important in nanotoxicology and nanomedicine. In this study, we use laser-scanning fluorescence confocal microscopy to evaluate nanoparticle penetration in viable excised human skin that was intact or tape-stripped. Quantum dot (QD) fluorescent nanoparticles with three surface modifications: Polyethylene glycol (PEG), PEG-amine (PEG-NH₂) and PEG-carboxyl (PEG-COOH) were evaluated for human skin penetration from aqueous solutions at pH 7.0 and at pHs of solutions provided by the QD manufacturer: 8.3 (PEG, PEG-NH₂) and 9.0 (PEG-COOH). There was some penetration into intact viable epidermis of skin for the PEG-QD at pH 8.3, but not at pH 7.0 nor for any other QD at the pHs used. Upon tape stripping 30 strips of stratum corneum, all QDs penetrated through the viable epidermis and into the upper dermis within 24 h.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.BIOMATERIALS.2010.02.022
Abstract: If skin's non-linear viscoelastic properties are mechanically exploited for precise antigen placement, there is tremendous promise for improved vaccines. To achieve this, we designed a Nanopatch-densely packed micro-nanoprojections (>20,000/cm(2)) to directly deposit antigen to large numbers of epidermal Langerhans cells and dermal dendritic cells. Here, we controllably applied our Nanopatches with discrete conditions between peak strain rates of approximately 100 s(-1)-7000 s(-1) and quantified resulting penetration depths, delivery payloads and skin mechanics. Increasing the strain rate of application, we overcame key skin variability, achieving increases in both projection penetration depth (by over 50% length) and area coverage of a full array (from 50% to 100%). This delivery depth precision opens the way for more fully utilizing the skin's immune function. Furthermore, we yielded new insights on mechanical behaviour of skin, including: 1) internal skin property changes that could affect/facilitate penetration 2) projection design to dictate penetration depth 3) puncture mechanics of skin in this strain rate range. Indeed, we show delivery of a model vaccine using our tested range of strain rates achieved functionally relevant tunable systemic antibody generation in mice. These findings could be of great utility in extending skin strata vaccine targeting approaches to human use.
Publisher: Public Library of Science (PLoS)
Date: 09-07-2013
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.JCONREL.2011.02.026
Abstract: Dry-coated microprojections can deliver vaccine to abundant antigen-presenting cells in the skin and induce efficient immune responses and the dry-coated vaccines are expected to be thermostable at elevated temperatures. In this paper, we show that we have dramatically improved our previously reported gas-jet drying coating method and greatly increased the delivery efficiency of coating from patch to skin to from 6.5% to 32.5%, by both varying the coating parameters and removing the patch edge. Combined with our previous dose sparing report of influenza vaccine delivery in a mouse model, the results show that we now achieve equivalent protective immune responses as intramuscular injection (with the needle and syringe), but with only 1/30th of the actual dose. We also show that influenza vaccine coated microprojection patches are stable for at least 6 months at 23°C, inducing comparable immunogenicity with freshly coated patches. The dry-coated microprojection patches thus have key and unique attributes in ultimately meeting the medical need in certain low-resource regions with low vaccine affordability and difficulty in maintaining "cold-chain" for vaccine storage and transport.
Publisher: MDPI AG
Date: 18-12-2022
DOI: 10.3390/BIOENGINEERING9120815
Abstract: The systemic administration of paclitaxel (PTX)-based combinatorial therapies is significantly restricted due to the multidrug resistance. Curcumin (CUR) not only inhibits cancer-cell proliferation but also reverses the PTX resistance. However, achieving codelivery of these two drugs is a challenge due to their poor water solubility. Herein, we synthesized carrier-free PTX NPs by a facile nanoprecipitation method with the help of CUR and other curcuminoids present in turmeric extract. The prepared NPs demonstrated spherical morphologies with high conformational stability. Experimental studies showed that the presence of both bisdemethoxycurcumin and demethoxycurcumin is essential for the successful formation of spherical and monodisperse NPs. Computational studies revealed that the presence of the more sterically available curcuminoids BMC and DMC makes the self-assembly procedure more adaptable with a higher number of potential conformations that could give rise to more monodisperse PTX-CUR NPs. Compared with PTX alone, PTX-CUR NPs have shown comparable therapeutic efficiency in vitro and demonstrated a higher cellular internalization, highlighting their potential for in vivo applications. The successful formation of PTX-CUR NPs and the understanding of how multiple drugs behave at the molecular level also provide guidance for developing formulations for the synthesis of high-quality and effective carrier-free nanosystems for biomedical applications.
Publisher: Wiley
Date: 16-12-2021
Abstract: With an exponential rise in antimicrobial resistance and stagnant antibiotic development pipeline, there is, more than ever, a crucial need to optimize current infection therapy approaches. One of the most important stages in this process requires rapid and effective identification of pathogenic bacteria responsible for diseases. Current gold standard techniques of bacterial detection include culture methods, polymerase chain reactions, and immunoassays. However, their use is fraught with downsides with high turnaround time and low accuracy being the most prominent. This imposes great limitations on their eventual application as point‐of‐care devices. Over time, innovative detection techniques have been proposed and developed to curb these drawbacks. In this review, a systematic summary of a range of biosensing platforms is provided with a strong focus on technologies conferring high detection sensitivity and specificity. A thorough analysis is performed and the benefits and drawbacks of each type of biosensor are highlighted, the factors influencing their potential as point‐of‐care devices are discussed, and the authors' insights for their translation from proof‐of‐concept systems into commercial medical devices are provided.
Publisher: Wiley
Date: 04-04-2011
DOI: 10.1111/J.1600-0625.2010.01234.X
Abstract: Skin is subjected regularly to mechanical stimulus. Surprisingly, when studying the use of microneedle arrays to introduce antigen into skin, we observed that mechanical stimulus to skin achieved by application of the arrays or a flat metal plate resulted in temporary depletion of Langerhans cells, with the degree of depletion related to the applied stress, whereas no depletion was seen in the interspersed dendritic epidermal T cell population. Further, a significantly impaired immune response to intracutaneous antigen administration was observed in skin recently subjected to mechanical stimulus. This observation may have implications for selection of sites of skin immunisation and for immunogenicity of infections at skin sites routinely subjected to mechanical stimuli.
Publisher: American Chemical Society (ACS)
Date: 17-04-2019
DOI: 10.1021/ACS.BIOMAC.9B00494
Abstract: Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n-π* transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC00166B
Abstract: Nano photodynamic therapy to overcome multidrug resistant bacteria.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4CC06659F
Abstract: Graphitic carbon nitride hybrid nanofilms are reported as sensitive, rapid and recyclable sensor for Cu 2+ and Ag + , and the sensing in serum demonstrates their potential in medical applications.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Xianfeng Chen.