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Arai S.,Waseda Bioscience Research Institute in Singapore WABIOS | Arai S.,Waseda University | Lee C.-L.K.,Center for Life Science Enterprise | Chang Y.-T.,National University of Singapore | And 3 more authors.
RSC Advances | Year: 2015

Control of cargo release from nanoscale carriers is an important technology for maximizing the benefits of nanoparticulate drug delivery systems. Herein, we attempt to trigger the release of cargo from liposomes by photothermal conversion of water with a 980 nm near-infrared (NIR) laser. This study examined liposomes of two types formulated by 1,2-dipalmitory-sn-glycero-3-phosphocholine (DPPC) or a mixture of DPPC/cholesterol with an anionic lipid and PEG-lipid as stabilizers encapsulating calcein as a cargo at different ionic strengths. Liposome formulation encapsulating a hypertonic solution with a lipid membrane shows that a gel to liquid-crystalline phase transition at around 40 °C effectively released the cargo from liposomes at temperature above 40 °C with NIR irradiation. Our proof of concept has been further demonstrated in a cancer cell with monitoring the actual "intracellular temperature" using a fluorescent thermosensor. Intracellular thermometry revealed that it was not until the intracellular temperature reached around 40 °C by NIR irradiation that the release of the cargo started gradually, showing good agreement with the result from the extracellular in vitro study. This targeted release of cargo from thermosensitive liposomes based on a photothermal effect using a NIR laser offers a potent nanoscale platform for the on-demand release of drugs in intracellular space with local hyperthermia. The intracellular thermometry facilitates the quantitative monitoring and control of the hyperthermia at the cellular level. © 2015 The Royal Society of Chemistry.

Lee S.-K.,Center for Life Science Enterprise | Chwee J.Y.,Center for Life Science Enterprise | Chwee J.Y.,National University of Singapore | Ma C.A.P.,Center for Life Science Enterprise | And 4 more authors.
Clinical Cancer Research | Year: 2014

Purpose: The low immunogenicity of many cancer cells and the immunosuppression by various cancers and anticancer therapies have been an obstacle in the development of efficacious immunotherapies. Our goal was to test whether Toll-like receptor (TLR) agonists and anticancer chemotherapeutic agents synergize in rendering tumor cells more immunogenic. Experimental Design: We treated B-cell lymphoma cells with the TLR1/2 agonist Pam 3CSK4 and the genotoxic anticancer agent 1-β-D-arabinofuranosylcytosine (Ara-C). The effects on the immunogenicity of tumor cells were measured in transfer experiments and in vitro studies. Results: The treatment of B-cell lymphoma cells with the TLR1/2 agonist Pam 3CSK4 enhanced the anticancer effects of the genotoxic agent Ara-C. Mice injected with cotreated tumor cells survived longer than mice challenged with Pam3CSK4 or Ara-C-treated cells. Administration of Pam3CSK4 or Ara-C reduced the tumor load of mice injected with tumor cells. Cotreatment had no effect on the rate of apoptosis or proliferation of Ara-C-treated cells, but upregulated the expression of several immunomodulatory molecules. Consistent with an increased immunogenicity of Pam3CSK4 and Ara-C-treated B-cell lymphoma cells, rejection of cotreated tumor cells required natural killer cells and T cells. We demonstrate that the upregulation of immunomodulatory molecules in response to Pam3CSK4 and Ara-C depended in part on NF-kB. Conclusion: TLR agonists can increase the efficacy of conventional cancer therapies by altering the immunogenicity of B-cell lymphoma cells. © 2014 American Association for Cancer Research.

Liu X.,Center for Life Science Enterprise | Cho B.,Nanyang Technological University | Chan L.-Y.,Center for Life Science Enterprise | Kwan W.L.,Singapore University of Technology and Design | Ken Lee C.-L.,Center for Life Science Enterprise
RSC Advances | Year: 2015

A new strategy of obtaining large Stokes shift squaraine dyes is reported. Archetypal near infrared squaraines typically have very sharp absorption peaks and small Stokes shifts due to their very rigid ground and excited state molecular structures. TDDFT calculations revealed that large Stokes shift in squaraines can be reached by structural relaxation of the excited state. We achieved Stokes shifts of 90 nm by introducing a dibutyl-aniline side group and an electron withdrawing dicyano group to the squarate core. Wavefunction analysis indicates that that steric interactions and mesomeric effects in the ground and excited states of squaraines are crucial in determining the Stokes shift of the dye. © The Royal Society of Chemistry.

PubMed | Center for Life Science Enterprise
Type: Journal Article | Journal: Stem cells translational medicine | Year: 2015

The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting-edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.

PubMed | Center for Life Science Enterprise
Type: Clinical Trial | Journal: The Journal of clinical endocrinology and metabolism | Year: 2012

Limited data suggest that testosterone is decreased during space flight, which could contribute to bone and muscle loss.The main objective was to assess testosterone and hormone status in long- and short-duration space flight and bed rest environments and to determine relationships with other physiological systems, including bone and muscle.Blood and urine samples were collected before, during, and after long-duration space flight. Samples were also collected before and after 12- to 14-d missions and from participants in 30- to 90-d bed rest studies.Space flight studies were conducted on the International Space Station and before and after Space Shuttle missions. Bed rest studies were conducted in a clinical research center setting. Data from Skylab missions are also presented.All of the participants were male, and they included 15 long-duration and nine short-duration mission crew members and 30 bed rest subjects.Serum total, free, and bioavailable testosterone were measured along with serum and urinary cortisol, serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and SHBG.Total, free, and bioavailable testosterone was not changed during long-duration space flight but were decreased (P < 0.01) on landing day after these flights and after short-duration space flight. There were no changes in other hormones measured. Testosterone concentrations dropped before and soon after bed rest, but bed rest itself had no effect on testosterone.There was no evidence for decrements in testosterone during long-duration space flight or bed rest.

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