| 2. |
- Chen, Yan-Ting, et al.
(author)
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Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation
- 2023
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In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 15:27, s. 32967-32983
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Journal article (peer-reviewed)abstract
- Due to the mortality associated with thrombosis and its highrecurrence rate, there is a need to investigate antithrombotic approaches.Noninvasive site-specific thrombolysis is a current approach being used; however,its usage is characterized by the following limitations: low targeting efficiency, poorability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms,and risk of thrombus recurrence that is comparable to that of traditionalpharmacological thrombolysis agents. Therefore, it is vital to develop an alternativetechnique that can overcome the aforementioned limitations. To this end, a cottonball-shaped platelet (PLT)-mimetic self-assembly framework engineered with aphototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has beendeveloped. This platform is capable of delivering a synthetic peptide derived fromhirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors fornoninvasive site-specific thrombolysis, effective anticoagulation, and vascularrestoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequentlyrupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability ofthe P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancingbioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extendedcirculation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination cansignificantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultantphototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLTnanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.
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| 3. |
- Lee, I-Ming, et al.
(author)
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A hexasaccharide from capsular polysaccharide of carbapenem-resistant Klebsiella pneumoniae KN2 is a ligand of Toll-like receptor 4
- 2022
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In: Carbohydrate Polymers. - : ELSEVIER SCI LTD. - 0144-8617 .- 1879-1344. ; 278
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Journal article (peer-reviewed)abstract
- Klebsiella pneumoniae serotype KN2 is a carbapenem-resistant strain and leads to the health care-associated in-fections, such as bloodstream infections. Its capsular polysaccharide (CPS) was isolated and cleaved by a specific enzyme from a bacteriophage into a hexasaccharide-repeating unit. With GC-MS, NMR, and Mass analyses, the structure of KN2 CPS was determined to be {-> 3)-beta-D-Glcp-(1 -> 3)-[alpha-D-GlcpA-(1 -> 4)-beta-D-Glcp-(1 -> 6)]-alpha-D-Galp- (1 -> 6)-beta-D-Galp-(1 -> 3)-beta-D-Galp-(1 ->}(n). We demonstrated that 1 mu g/mL CPS could stimulate J774A.1 murine macrophages to release tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in vitro. Also, we proved that KN2 CPS induced the immune response through Toll-like receptor 4 (TLR4) in the human embryonic kidney (HEK)-293 cells. Strikingly, the hexasaccharide alone shows the same immune response as the CPS, suggesting that the hexasaccharide can shape the adaptive immunity to be a potential vaccine adjuvant. The glucuronic acid (GlcA) on other polysaccharides can affect the immune response, but the GlcA-reduced KN2 CPS and hex-asaccharide still maintain their immunomodulatory activities.
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| 4. |
- Zhou, Yixuan, et al.
(author)
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Effective Organotin-Mediated Regioselective Functionalization of Unprotected Carbohydrates
- 2023
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In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 88:11, s. 7174-7151
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Journal article (peer-reviewed)abstract
- Regioselective functionalization of unprotected carbohydrates at a secondary OH group in the presence of primary OH groups based on the commonly used organotin-mediated reaction has been improved. We found that the preactivation of the dibutylstannylene acetal intermediate with tetrabutylammonium bromide in toluene is a key to the improved condition for the efficient, high-yielding, and regioselective tosylation, benzoylation, or benzylation of unprotected carbohydrates. The counteranion of tetrabutylammonium ion with a weak coordination ability plays a crucial role in the improved regioselective reactions. A convenient access to the intermediates of synthetic value is also demonstrated in the organotin-mediated regioselective tosylation of unprotected carbohydrates, followed by the nucleophilic inversion reaction to give sulfur-containing and azide-modified carbohydrates.
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