Fangyuan Li

Multiple‐Interaction Ligands Inspired by Mussel Adhesive Protein: Synthesis of Highly Stable and Biocompatible Nanoparticles

Theprerequisiteforthesuccessfulbiomedicaluseofnanoparticles is their colloidal stability in harsh biologicalenvironments. One main approach to render nanoparticleswater-dispersible is replacing the hydrophobic cappingligands with hydrophilic ones that harbor anchoring groupssuch as carboxylic acids, thiols, phosphines, and amines;

Hyaluronic acid-conjugated graphene oxide/photosensitizer nanohybrids for cancer targeted photodynamic therapy

Hyaluronic acid (HA)-graphene oxide (GO) conjugates, with a high loading of photosensitizers (PS; Ce6), were developed as a cancer cell targeted and photoactivity switchable nanoplatform for photodynamic therapy (PDT). HA-GO conjugates with size below 100 nm were first prepared by the chemical conjugation between ADH-modified HA and fractionated GO sheets with size relevant for drug delivery. Before evaluating the drug delivery efficacies, their chemical structure, morphology, and biocompatibility were characterized by 1H NMR, UV, TGA, AFM, DLS and MTT assays. The physical adsorption of Ce6 onto HA-GO nanocarriers was mainly due to the π-π stacking as well as hydrophobic interactions. It was demonstrated by CLSM and FACS that the cellular internalization of the HA-GO/Ce6 nanohybrids was much more effective when compared with free Ce6, which was also found to be significantly influenced by the co-treatment with an excess amount of HA polymers, illustrating their active targeting to HA receptors overexpressed on cancer cells. The photoactivity of Ce6 adsorbed on HA-GO nanocarriers was mostly quenched in aqueous solution to ensure biocompatibility, but was quickly recovered after the release of Ce6 from HA-GO nanocarriers upon cellular uptake. As a result, the PDT efficiency of the HA-GO/Ce6 nanohybrids was remarkably improved ∼10 times more than that of free Ce6, as well demonstrated in both MTT and LIVE/DEAD assays.

Acetylated hyaluronic acid/photosensitizer conjugate for the preparation of nanogels with controllable phototoxicity: synthesis, characterization, autophotoquenching properties, and in vitro phototoxicity against HeLa cells.

A proposal is herein examined for a novel yet simple design of a polymeric nanogel, with tumor targeting properties and a controllable phototoxicity, utilizing a low molecular weight-hyaluronic acid (HA(LM))/photosensitizer conjugate. HA(LM) was acetylated prior to being dissolved in DMSO (Ac-HA(LM)) and then was conjugated with different amounts of pheophorbide a (Pba), resulting in the formulation of self-organizing nanogels in aqueous solutions (Ac-HA-Pba 1, 2, and 3). The nanogels observed were below 200 nm in size, with a monodispersed size distribution. The nanogels displayed auto photoquenching qualities in PBS, while their fluorescent intensity strongly correlated with the amount of Pba in the organic solvent (DMSO or DMF). The critical self-quenching concentration (CQC) of the conjugates was found to have decreased as the content of Pba rose. Although Pba was conjugated with HA, the nanogels photoactivity, in terms of fluorescent properties, singlet oxygen generation, and photocytotoxicity, was approximately maintained. Confocal imaging and FACS analysis showed that Ac-HA-Pba nanogels were rapidly internalized into HeLa cells via an HA-induced endocytosis mechanism, a process which could be blocked with the application of an excess of HA polymer. The results of the study indicate that HA-based nanogels can potentially be applied in photodynamic therapy (PDT).

Surface design of magnetic nanoparticles for stimuli-responsive cancer imaging and therapy

Magnetic nanoparticles (MNPs) have been extensively studied for their potential applications to cancer diagnosis and treatment. However, various obstacles limit the use of nanoparticles for delivery in the tumor microenvironment. As a viable solution to such obstacles, advances in nanoparticle surface engineering augmented by a profound understanding of cancer physiology present new opportunities for MNP-based imaging and therapeutic agents. Stimuli-responsive ligands, rationally designed to interact with various physicochemical aspects, can improve the performance of MNPs in cancer-targeted imaging and therapy. In this review, we highlight recent progress in the design of MNP-based stimuli-responsive nanomaterials and their applications to cancer diagnosis and treatment.

Unilateral transforaminal lumbar interbody fusion: a review of the technique, indications and graft materials.

Transforaminal lumbar interbody fusion (TLIF) is an alternative interbody fusion procedure in which interbody space is accessed via a path that runs through the far lateral portion of the vertebral foramen. TLIF reduces the potential complications of other approaches, including the transabdominal approach or posterior lumbar interbody fusion (PLIF), but still achieves clinical outcomes and circumferential fusion results comparable with PLIF. Operative indications for TLIF are contested among many spine experts. The optimal indications for using this technique are spondylolisthesis, degenerative disc disease with a specific discogenic pain pattern, lumbar stenosis with instability and recurrent lumbar disc herniation with radiculopathy. Various instrumentation techniques and graft materials are available to use in TLIF, and each option has benefits and disadvantages. Further research is needed, however, TLIF with one cage and excised local bone and augmented with a bilateral pedicle screw seems to be an effective and affordable treatment.

pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma

Response rates to conventional chemotherapeutics remain unsatisfactory for hepatocellular carcinoma (HCC) due to the high rates of chemoresistance and recurrence. Tumor-initiating cancer stem-like cells (CSLCs) are refractory to chemotherapy, and their enrichment leads to subsequent development of chemoresistance and recurrence. To overcome the chemoresistance and stemness in HCC, we synthesized a Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters incorporating a pH-sensitive polymer and HCC-targeting peptide. Pt-NA is latent in peripheral blood, readily targets disseminated HCC CSLCs, and disassembles into small Pt nanoclusters in acidic subcellular compartments, eventually inducing damage to DNA. Furthermore, treatment with Pt-NA downregulates a multitude of genes that are vital for the proliferation of HCC. Importantly, CD24+ side population (SP) CSLCs that are resistant to cisplatin are sensitive to Pt-NA, demonstrating the immense potential of Pt-NA for treating chemoresistant HCC.

Iron oxide nanoclusters for T 1 magnetic resonance imaging of non-human primates

Iron-oxide-based contrast agents for magnetic resonance imaging (MRI) had been clinically approved in the United States and Europe, yet most of these nanoparticle products were discontinued owing to failures to meet rigorous clinical requirements. Significant advances have been made in the synthesis of magnetic nanoparticles and their biomedical applications, but several major challenges remain for their clinical translation, in particular large-scale and reproducible synthesis, systematic toxicity assessment, and their preclinical evaluation in MRI of large animals. Here, we report the results of a toxicity study of iron oxide nanoclusters of uniform size in large animal models, including beagle dogs and the more clinically relevant macaques. We also show that iron oxide nanoclusters can be used as T1 MRI contrast agents for high-resolution magnetic resonance angiography in beagle dogs and macaques, and that dynamic MRI enables the detection of cerebral ischaemia in these large animals. Iron oxide nanoclusters show clinical potential as next-generation MRI contrast agents.Uniform iron oxide nanoparticle clusters are highly biocompatible and can be used as contrast agents for high-resolution magnetic resonance angiography of large animals.

Surgery is an Effective and Reasonable Treatment for Degenerative Scoliosis: A Systematic Review

OBJECTIVE: A systematic review to evaluate the role of surgery for treating degenerative scoliosis (DS) in terms of improved function (Oswestry Disability Index [ODI]) and correction of deformity (Cobb angle); safety outcomes included complication and repeat surgery rates. METHODS: A search of the MEDLINE, ISI Web of Knowledge and Cochrane Library databases was performed. The methodological quality of each study was assessed according to standardized criteria and data were extracted. RESULTS: A total of 16 studies including 553 patients with DS met the eligibility criteria for inclusion. The mean ODI score at final follow-up was 36.0 ± 7.8 (304 patients) and the mean decrease in ODI was 23.3 ± 11.3 (302 patients). Mean reduction in curve angle (as a percentage of the original curve) was 48.5 ± 21.0% (527 patients). The overall incidence of complications was 49.0% (171 in 349 patients) and the rate of repeat surgery was 15.3% (61 in 398 patients). CONCLUSIONS: Despite a high incidence of complications and reoperations, surgery was an effective and reasonable treatment for DS, providing significant functional improvement and deformity correction.

A Facile Approach to Prepare Tough and Responsive Ultrathin Physical Hydrogel Films as Artificial Muscles

We report a facile approach to prepare ultrathin physical hydrogel films based on the Marangoni effect, which drives an ethanol solution of poly(stearyl acrylate-co-acrylic acid) (P(SA-co-AAc)) to rapidly spread on the water surface. The subsequent solvent exchange leads to sol-gel transition, where the long alkyl chains of SA units segregate to form physical cross-linking junctions. The resultant disk-shaped single-network (SN) gel films are uniform with tunable thickness (40-80 μm) and diameter (5-12 cm) and possess robust mechanical properties with tensile breaking stress, σb, and breaking strain, εb, being 0.3-1.1 MPa and 30-290%, respectively. The mechanical properties of SN gel films can be further improved by introducing ductile poly(N-isopropylacrylamide) (PNIPAm) into the preformed gel matrix, which forms strong hydrogen bonds with the first network. The obtained physical double-network (DN) hydrogel films are transparent and show excellent mechanical performances with σb of 3-5 MPa and εb of 100-500%. Due to the ultrathin thickness of gel films and response of PNIPAm to saline solutions, the tough DN gel films exhibit fast response (≤60 s) and large stroke force (0.5 MPa) after switching the environment from water bath to saline solution, making them an ideal material to design artificial muscles, soft actuators, and chemomechanical devices.

New hypothesis of chronic back pain: low pH promotes nerve ingrowth into damaged intervertebral disks

The pathogenesis of low back pain is still elusive. Here, we proposed a new hypothesis that low pH is a possible cause of the development and progression of low back pain. We propose that low pH promotes the production of the inflammatory mediators and the depletion of proteoglycan in the damaged intervertebral disk. The inflammation response, evoked by the dorsal root ganglia, changes the delicate nutrient balance in the nucleus, resulting in a vicious cycle and leading to choronic back pain. Our hypothesis may explain many of the available clinical and experimental data on low back pain, thus it may help elucidate the pathogenesis of low back pain and improve clinical management.