Jun Wu

Bio: Jun Wu is an academic researcher from Sun Yat-sen University. The author has contributed to research in topics: Drug delivery & Self-healing hydrogels. The author has an hindex of 53, co-authored 189 publications receiving 12007 citations. Previous affiliations of Jun Wu include Third Military Medical University & Southwest General Health Center.

Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds

Abstract: The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for the long-term efficient biomechanical function. These are, however, challenging to mimic in de novo engineered living tissue valve strategies. We present a novel simultaneous 3D printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12-22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over tenfold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 min, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0 and 73.3±5.2% for 22, 17 and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6 and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment.

DNA self-assembly of targeted near-infrared-responsive gold nanoparticles for cancer thermo-chemotherapy.

Abstract: The development of external stimulus-responsive nanoparticle (NP) systems for cancer therapy has received considerable attention in recent years, as these systems can differentially increase drug accumulation at target cancer cells/tissues, drastically decrease systemic toxicity, and potentially avoid underor over-dosing. External stimuli that have been exploited for such applications include light, magnetic field, ultrasound, and electricity. Among them, nearinfrared (NIR) light (650–900 nm) has recently become an attractive stimulus because of its minimal absorbance by skin and tissue, thus allowing for noninvasive and deep tissue penetration. In particular, NIR light can be effectively converted into heat by using photothermal NPs, such as gold nanorods (NRs), gold nanoshells, hollow gold nanospheres, and carbon nanotubes. As such, NIR-responsive NP platforms offer several important benefits for cancer therapy. For example, NIR-induced local heating can be used for cancer thermotherapy. In addition, NIR-responsive NP delivery systems enable on-demand release of drugs for cancer chemotherapy, presumably by heat-induced disruption of the delivery vehicles. Furthermore, the combination of NIR-based thermotherapy and triggered chemotherapy (thermo-chemotherapy) could provide higher therapeutic efficacy than respective monotherapies. In addition to these advantages, investigators are exploring the possibility of integrating active targeting ligands in NIR-responsive NP platforms for targeted cancer thermochemotherapy. This triple combination of thermotherapy, triggered drug release, and targeted delivery, would achieve optimal therapeutic efficacy in cancer treatment, relative to pairwise combinations. For example, Lee et al. have designed folate-conjugated, doxorubicin (Dox) loaded poly(lactic-co-glycolic acid) (PLGA)–gold half-shell NPs, and this combination led to effective tumor elimination in target tissues in a NIR-responsive manner. A current strategy in formulating this targeted NIR-responsive NP requires multiple steps, including 1) the synthesis of drug-loaded NPs, 2) deposition of gold compositions on NPs, and 3) postconjugation with targeting ligands followed by purification. However, these complex processes could increase the difficulty of adjusting bio-physicochemical properties of NPs in a reproducible manner, and could contribute to unintended drug release from NPs, thereby resulting in unfavorable batch-to-batch variability in the characteristics of drug loading. Alternatively, using pre-functionalized components to self-assemble into targeted NPs would eliminate the need for post-modification of NPs and is amenable to being scaledup with little batch-to-batch variability. This self-assembly strategy has led to the clinical translation of first-in-man targeted cyclodextrin-based NPs for small interfering RNA (siRNA) delivery, and targeted PLGA-based NPs for docetaxel delivery. Nevertheless, use of such a self-assembly strategy in the design of targeted NIR-responsive NPs has not been reported to date. Inspired by nature and the ability of complimentary strands of DNA to hybridize, we designed a DNA-based platform that can self-assemble into targeted NIR-responsive NPs for cancer therapy. As illustrated in Figure 1, this platform comprises three distinct functional components: complementary DNA strands, the gold NR (50 nm 10 nm), and a polyethylene glycol (PEG) layer. The DNA strands, which consist of sequential CG base pairs, provide loading sites for Dox, a model chemotherapeutic drug. By changing the number of CG base pairs, drug loading can be precisely tuned. In addition to serving as drug-loading scaffold, one strand of the DNA (termed capture strand) is thiolated for gold NR capture, and the complementary strand (termed targeting strand) is pre-conjugated with ligands for cellspecific targeting. Gold NRs serve as the model NIR light-to[*] Dr. Z. Xiao, Dr. C. Ji, Dr. J. Shi, J. Frieder, Dr. J. Wu, Prof. O. C. Farokhzad Laboratory of Nanomedicine and Biomaterials Department of Anesthesiology, Brigham and Women’s Hospital Harvard Medical School, Boston, MA, 02115 (USA) E-mail: ofarokhzad@zeus.bwh.harvard.edu

Myotube assembly on nanofibrous and micropatterned polymers.

Abstract: Skeletal muscle consists of parallel bundles of myotubes formed by the fusion of myoblasts. We fabricated nanofibrous and micropatterned polymers as cell culture substrates to guide the morphogenesis of muscular tissue. The nanoscale and microscale topographic features regulate cell and cytoskeleton alignment, myotube assembly, myotube striation, and myoblast proliferation. This bottom-up approach from nanoscale to tissue level demonstrates the potential of nanofibrous polymers for engineering the assembly of cell and tissue structure.

Stimuli-responsive nanocarriers for drug delivery

Abstract: Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).

Principles of nanoparticle design for overcoming biological barriers to drug delivery

Abstract: Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

Cancer nanomedicine: progress, challenges and opportunities.

Abstract: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

Nano based drug delivery systems: recent developments and future prospects

Abstract: Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc) in the treatment of various diseases The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (eg, natural products) and selective diagnosis through disease marker molecules The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed In addition, we have included information regarding the trends and perspectives in nanomedicine area