Biomaterials. 2013 Dec;34(36):9115-23.   doi: 10.1016/j.biomaterials.2013.08.020.   Epub 2013 Aug 24. Site-specific PEGylation of a mutated-cysteine residue and its effect on tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) Li-Qiang Pan 1, Hai-Bin Wang, Jun Lai, Ying-Chun Xu, Chen Zhang, Shu-Qing Chen Abstract Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising antitumor agent that specifically induces apoptosis in broad-spectrum tumor cell lines, meanwhile leaving normal cells unaffected.   Unfortunately, the clinical development of TRAIL was hampered, and could be attributed to its instability, bioavailability or poor delivery.   Although N-terminal specific PEGylation provides a means to improve the pharmacokinetic and stability of TRAIL, it took a bit longer time to accomplish the PEGylation process than expected.   We therefore designed another PEGylation approach, mutated Cys-SH site-specific PEGylation, to conjugate methoxypoly(ethylene glycol) maleimide (mPEG-MAL) with TRAIL (95-281) mutant N109C.   Asn-109 was chosen as the PEGylated site for it is a potential N-linked glycosylation site.   It was shown that ~90% TRAIL mutant N109C could be PEGylated by mPEG-MAL within 40 min. And mPEG(MAL)-N109C was revealed to possess superior in vitro stability and antitumor activity than N-terminal specifically PEGylated TRAIL (114-281) (mPEG(ALD)-TRAIL(114-281)).   What's more, mPEG(MAL)-N109C exhibited more therapeutic potentials than mPEG(ALD)-TRAIL(114-281) in tumor xenograft model, benefitting from better drug delivery and bioavailability.   These results have demonstrated mutated Cys-SH specific PEGylation is an alternative to site-specifically PEGylate TRAIL efficiently and effectively other than N-terminal specific PEGylation. Keywords: Antitumor agent;   Glycosylation site;   PEG-TRAIL;   Protein delivery;   Site-specific PEGylation. Related products Abbreviation: mPEG-pALD Name: Methoxypoly(ethylene glycol) propionaldehyde Abbreviation: mPEG-MAL Name: Methoxypoly(ethylene glycol) maleimide For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

ACS Appl Mater Interfaces. 2020 Feb 26;12(8):9132-9140. doi: 10.1021/acsami.0c01022. Epub 2020 Feb 14. An Injectable and Instant Self-Healing Medical Adhesive for Wound Sealing Feifei Sun 1, Yazhong Bu 1, Yourong Chen 2, Fei Yang 1, Jiakuo Yu 2, Decheng Wu 1 3 Abstract Designing versatile functional medical adhesives with injectability, self-healing, and strong adhesion is of great significance to achieve desirable therapeutic effects for promoting wound sealing in healthcare. Herein, a self-healing injectable adhesive is fabricated by physical interaction of polyphenol compound tannic acid (TA) and eight-arm poly(ethylene glycol) end-capped with succinimide glutarate active ester (PEG-SG). The hydrogen bonding induced from the structural unit (-CH2-CH2-O-) of PEG and catechol hydroxyl (-OH) of TA, accompanied by ester exchange between N-hydroxysuccinimide (-NHS) and amino (-NH2) of proteins, contributes to self-healing ability and rapid strong adhesion. Notably, the PEG/TA adhesive can repeatedly adhere to rigid porcine tissues, close the coronary artery under a large incision tension, and bear a heavy load of 2 kg. By exhibiting shear-thinning and anti-swelling properties, the PEG/TA adhesive can be easily applied through single-syringe extrusion onto various wounds. The single-channel toothpaste-like feature of the adhesive ensures its storage hermetically for portable usage. Moreover, in vivo operation and histological H&E staining results indicate that the PEG/TA adhesive greatly accelerates wound healing and tissue regeneration in a rat model. With the specialty of injectability, instant self-healing, and long-lasting strong adhesion to facilitate excellent therapeutic effects, the multifunctional PEG/TA adhesive may provide a new alternative for self-rescue and surgical situations. Keywords: adhesive; poly(ethylene glycol); self-healing; single channel/injectable; wound sealing. Related products Abbreviation: mPEG-OH Name: Methoxypoly(ethylene glycol) Abbreviation: mPEG-NH2 Name: Methoxypoly(ethylene glycol) amine Abbreviation: mPEG-SH Name: Methoxypoly(ethylene glycol) thiol For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

ACS Nano. 2019 Nov 26;13(11):12912-12928. doi: 10.1021/acsnano.9b05425. Epub 2019 Oct 29. Tumor Microenvironment Responsive Shape-Reversal Self-Targeting Virus-Inspired Nanodrug for Imaging-Guided Near-Infrared-II Photothermal Chemotherapy Yang Li 1 2 3, Jinyan Lin 2, Peiyuan Wang 1 2 3, Qiang Luo 1 2 3, Huirong Lin 4, Yun Zhang 1 3, Zhenqing Hou 5, Jingfeng Liu 1 2 3, Xiaolong Liu 1 2 3 Abstract Tumor microenvironment responsive multimodal synergistic theranostic strategies can significantly improve the therapeutic efficacy while avoiding severe side effects. Inspired by the fact that special morphology could enhance photothermal conversion efficiency (PCE) and cellular delivery, we developed an acidic tumor microenvironment responsive shape-reversal metal-organic virus-inspired nanodrug for enhancing near-infrared (NIR)-II PCE, increasing cell adhesion, and activating tumor targeting. First, a NIR-I fluorescence probe (IR825), a chemo-drug (pemetrexed, PEM), and a rare-earth metal ion (Nd(III)) were chosen to synthesize a virus-like nanodrug via coordination-driven assembly. Then, the spike-like surface of the nanodrug was further camouflaged by an acidity-sensitive poly(ethylene glycol) "shell" to create virus-core and sphere-shell hierarchical nanoassemblies, which could efficiently prevent immune clearance and prolong systemic circulation. Interestingly, the acidic tumor microenvironment could trigger the shell detachment of nanoassemblies for shape reversal to produce a virus-like surface followed by re-exposure of PEM to synergistically amplify the cellular internalization while enhancing NIR-II PCE. By utilizing the shell-detached virus-like nanodrug core, the tumor microenvironment specific enhanced NIR-II photothermal chemotherapy can be realized under the precise guidance of fluorescence/photoacoustic imaging, thereby achieving complete tumor elimination without recurrence in a single treatment cycle. We envision that integrating the tumor microenvironment responsive ability with "sphere-to-virus" shape reversal will provide a promising strategy for biomimetic targeted cancer therapy. Keywords: NIR-II photothermal therapy; chemotherapy; shape reversal; tumor microenvironment response; virus-inspired nanodrug. Related products Abbreviation: mPEG-OH Name: Methoxypoly(ethylene glycol) For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Nanomicro Lett. 2020 Sep 14;12(1):182. doi: 10.1007/s40820-020-00492-4. Tumor Microenvironment Cascade-Responsive Nanodrug with Self-Targeting Activation and ROS Regeneration for Synergistic Oxidation-Chemotherapy Yang Li # 1 2 3, Jinyan Lin # 2, Peiyuan Wang 1 2 3, Qiang Luo 1 2 3, Fukai Zhu 4, Yun Zhang 1 3, Zhenqing Hou 4, Xiaolong Liu 5 6 7, Jingfeng Liu 8 9 10 Abstract Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions. Herein, we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop. The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate (MTX) self-assembles into nanoparticles (VSeM); decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time. Upon reaching tumor sites, acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake. Afterward, the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release; then the released VES could produce extra ROS to accelerate the collapse of VSeM. Finally, the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy. Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment. Keywords: Circular amplification of ROS; Positive-feedback loop; Synergistic oxidation-chemotherapy; Targeting activation; Vitamin E nanodrug. Related products Abbreviation: mPEG-OH Name: Methoxypoly(ethylene glycol) For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Biotechnol Lett. 2016 Jul;38(7):1121-9. doi: 10.1007/s10529-016-2083-6. Epub 2016 Mar 29. PEGylation of cytochrome c at the level of lysine residues mediated by a microbial transglutaminase Jian Qin Zhou 1, Ting He 1, Jian Wen Wang 2 Abstract Objectives: To establish a method for microbial transglutaminase (mTG)-mediated PEGylation of proteins at the level of lysine (Lys) residues. Results: Carboxybenzyl-glutaminyl-glycinyl-methoxypolyethylene glycol (CBZ-QG-mPEG) was prepared by introducing carboxybenzyl-glutaminyl-glycine (CBZ-QG) to mPEG amine. The analysis by Fourier transform infrared spectroscopy and SDS-PAGE showed that CBZ-QG-mPEG was successfully synthesized and can be recognized by mTG as an acyl donor to modify therapeutic protein, cytochrome c (cyt c). Finally, under an optimized condition (cyt c 0.5 mg/ml, CBZ-QG-mPEG 11.25 mg/ml, mTG 0.5 mg/ml, 37 °C, 2 h), the PEGylation yield reached 76.5 %. Conclusions: This is the first study regarding the PEGylation of protein at the level of Lys residues catalyzed by mTG. The novel method could be employed to immobilize active proteins and modify therapeutic proteins. Keywords: Lysine residue; Microbial transglutaminase; PEGylation; Therapeutic protein; Transglutaminase. Related products Abbreviation: mPEG-NH2 Name: Methoxypoly(ethylene glycol) amine Abbreviation: mPEG-SPA Name: Methoxypoly(ethylene glycol) succinimidyl propionate For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Published: 16 May 2018;   DOI:10.1007/s40242-018-8023-3 Chemical Research in Chinese Universities volume 34, pages428–433 (2018) Site-specific PEGylation of Human Growth Hormone by Mutated Sortase A Hui Shi, Qingyang Shi, James T. Oswald, Ying Gao, Leijiao Li & Yunhui Li Abstract Human growth hormone(hGH), a classic therapeutic protein, which promotes growth and wound healing, is released from the pituitary gland.   As a protein drug, its short half-life is its main barrier to therapeutic efficacy.   Various strategies have been designed to prolong its serum half-life, the most common of which is the conjugation with polyethylene glycol(PEG), as this has been shown to significantly extend protein’s serum half-life.   However, PEGylation often results in random conjugation, which can lead to impaired protein function and hinder purification, characterization and evaluation of the PEGylated protein.   Therefore, site specific PEGylation is a promising direction for PEG-protein conjugation.   Here we took advantages of the mutated sortase A(7M) enzyme, which can enzymatically ligate the universal α-amino acids to a C-terminal tagged protein.   This then allows specific modification of the C-terminal of hGH with PEG.   This site-specific bound PEG-hGH has similar efficacy, receptor binding and cell proliferation as wild-type hGH;   however, pharmacokinetic analysis demonstrates that its serum half-life is almost 24 times that of wild-type hGH.   Herein, we provided a promising advancement in the development of site specific PEGylated therapeutic proteins. Related products Abbreviation: mPEG-NH2 Name: Methoxypoly(ethylene glycol) amine For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Sci Total Environ. 2020 Apr 1;711:134493.   doi: 10.1016/j.scitotenv.2019.134493.   Epub 2019 Oct 4. RhB-encapsulating silica nanoparticles modified with PEG impact the vascular endothelial function in endothelial cells and zebrafish model Shuang Liang 1, Yueyue Chen 1, Shiming Zhang 2, Yuanyuan Cao 1, Junchao Duan 3, Yapei Wang 4, Zhiwei Sun 5 Abstract Silica nanoparticles (SiNPs) have been widely used in human health related products, such as food additives, cosmetics and even drug delivery, gene therapy or bioimaging.   Recently, a first-in-human clinical trial based on polyethylene glycol (PEG)-modified SiNPs had been approved by US FDA to trace melanoma.   However, as a nano-based drug delivery system, its biocompatibility and vascular toxicity are still largely unknown.   Thus, we synthesized the fluorescent SiNPs to explore the biocompatibility and vascular endothelial function, and compare different biological effects caused by PEG-modified and unmodified SiNPs in cells and zebrafish model.   The characterizations of SiNPs and PEG-modified SiNPs were analyzed by TEM, SEM, AFM and DLS, which exhibited relatively good stable and dispersive.   Compared with SiNPs, PEG-modified SiNPs had markedly reduced the inflammatory response and vascular damage in Tg (fli-1: EGFP) and Tg (mpo: GFP) transgenic zebrafish lines, respectively.   Consistent with the in vivo results, the PEG-modified SiNPs had been found to significantly decline the levels of ROS, inflammatory cytokines and mitochondrial-mediated apoptosis in vascular endothelial cells compared to SiNPs, and the ROS scavenger NAC could effectively alleviate the above adverse effects induced by nanoparticles.   Our results suggested that the PEG-modified SiNPs could become more safety via increasing the biocompatibility and decreasing cellular toxicities in living organisms. Keywords: Endothelial cells;   PEG modification;   RhB-encapsulating SiNPs;   Vascular function;   Zebrafish. Related products Abbreviation: mPEG-NH2 Name: Methoxypoly(ethylene glycol) amine For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

J Control Release. 2018 Mar 28;274:56-68. doi: 10.1016/j.jconrel.2018.01.034. Epub 2018 Feb 2. Reactive oxygen species-responsive nanoprodrug with quinone methides-mediated GSH depletion for improved chlorambucil breast cancers therapy Cheng-Qiong Luo 1, Yu-Xin Zhou 2, Tian-Jiao Zhou 3, Lei Xing 1, Peng-Fei Cui 3, Minjie Sun 3, Liang Jin 4, Na Lu 5, Hu-Lin Jiang 6 Abstract Prodrug-based stimuli-responsive vectors have emerged as highly promising platform. Inspired by the fact that antioxidant systems including glutathione (GSH) make cancer cells adapt to oxidative stress and play a role in the inactivation of alkylating agents like chlorambucil (CHL) inside tumor cells, while arylboronic acid could transform into GSH depleting agent quinone methide (QM) upon degradation by reactive oxygen species (ROS) over-expressed in tumor cells, a ROS-responsive nanoprodrug (denoted by PPAHC) of CHL was established by integrating CHL into diols-containing hydrophilic polymer with self-immolative linker 4-(hydroxymethyl)phenylboronic acid (HPBA). The prodrug could form core-shell nanoparticle and possess high stability during storage. Drug release profile of PPAHC nanoprodrug demonstrated that nature CHL could be quickly released from PPAHC nanoprodrug in the presence of hydrogen peroxide (H2O2). Moreover, PPAHC nanoprodrug showed improved therapeutic efficiency compared to CHL via anti-proliferative study and cell apoptosis assay. Further measurement of GSH content and ROS levels in tumor cells suggested that the synergistic impact resulted from QM-mediated GSH reduction and CHL-induced further oxidative stress insults to tumor cells. In vivo tumor suppression effect and biocompatibility indicated the superiorities of PPAHC nanoprodrug. Accordingly, PPAHC provides a new approach as a ROS-responsive CHL delivery system and has a great potential for cancer therapy. Keywords: Chlorambucil; Glutathione; Nanoprodrug; Quinone methide; Reactive oxygen species; Self-immolative linker. Related products Abbreviation: mPEG-NH2 Name: Methoxypoly(ethylene glycol) amine For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com