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

Journal of Nanomaterials | Volume 2015 | Article ID 541763 | https://doi.org/10.1155/2015/541763 Preparation and In Vitro Evaluation of a Multifunctional Iron Silicate@Liposome Nanohybrid for pH-Sensitive Doxorubicin Delivery and Photoacoustic Imaging Zehua Liu, Shaoheng Tang, Zhiran Xu, Yingjun Wang, Xuan Zhu, Liang-cheng Li, Wanjin Hong, and Xiumin Wang Abstract For preventing premature drug release in neutral environment and avoiding them being trapped into the endosomal/lysosomal system, we developed a novel iron silicate@liposome hybrid (ILH) formulation, which can be used as a carrier to transport doxorubicin (DOX) in a pH-sensitive manner and to escape from endosomal/lysosomal trapping through “proton-sponge” effect.   The high intensity of photoacoustic signal from in vitro photoacoustic imaging (PAI) experiments suggests that it is a promising candidate for PAI agent, providing the potential for simultaneously bioimaging and cancer-targeting drug delivery.   Cytotoxicity of our formulation toward tumor cells was remarkably higher than free DOX (48.4±7.7% and 26.2±8.4%, P < 0.001).   Confocal laser scanning microscopy experiments showed the enhanced transportation and enrichment process of DOX in QSG-7703 cells.   Taking together, we developed an easy approach to construct a multifunctional anticancer drug delivery/imaging system with a potency as a PAI agent.   The strategy of combining drug carrier and imaging agent is an emerging platform for further construction of nanoparticle and may play a significant role in cancer therapy and diagnosis. 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 Biomed Nanotechnol. 2019 Feb 1;15(2):373-381. doi: 10.1166/jbn.2019.2693. Polymeric Micelles with Endosome Escape and Redox-Responsive Functions for Enhanced Intracellular Drug Delivery Jing Liu, Xixi Ai, Huaping Zhang, Weiling Zhuo, Peng Mi Abstract Efficient intracellular delivery of bioactive compounds into cancer cells is critically important for treatment, as some compounds only validate for therapy after entering cancer cells. The boron neutron capture therapy (BNCT) applies thermal neutron irradiation to react with 10B-compounds that existed inside cancer cells to generate secondary killing irradiations to eradicate cancer cells. The effective distance of the emitted secondary killing irradiations is as long as a cellular diameter, which requires the cellular uptake of 10B-compounds for efficient tumor BNCT. However, current clinical approved 10B-compound of sodium borocaptate (BSH) exhibits low cellular uptake by cancer cells, which limits the therapeutic efficacy. Herein, the multifunctional polymeric micelles with endosome escape and redox-responsive functions have been developed by self-assembly from the BSH-conjugated block copolymers for enhanced delivery of BSH into cancer cells. The BSH-loaded polymeric micelles (BSH/micelle) showed a hydrodynamic diameter around 50 nm, and the size distribution was monodisperse. The BSH/micelle were stable in normal physiological environment, while the BSH could be released in responding to high level of redox-potential in cancer cells. Besides, intracellular delivery of BSH was highly promoted by BSH/micelle through the endosome escape function of micelles, which further increased the tumor therapeutic efficacy by BNCT. 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

Int J Nanomedicine. 2017 Aug 16;12:5863-5877.     doi: 10.2147/IJN.S141982.     eCollection 2017. pH-sensitive and folic acid-targeted MPEG-PHIS/FA-PEG-VE mixed micelles for the delivery of PTX-VE and their antitumor activity Yan Di 1, Ting Li 1, Zhihong Zhu 1, Fen Chen 2, Lianqun Jia 2, Wenbing Liu 3, Xiumei Gai 1, Yingying Wang 1, Weisan Pan 1, Xinggang Yang 1 Abstract The aim of this study was to simultaneously introduce pH sensitivity and folic acid (FA) targeting into a micelle system to achieve quick drug release and to enhance its accumulation in tumor cells.     Paclitaxel-(+)-α-tocopherol (PTX-VE)-loaded mixed micelles (PHIS/FA/PM) fabricated by poly(ethylene glycol) methyl ether-poly(histidine) (MPEG-PHIS) and folic acid-poly(ethylene glycol)-(+)-α-tocopherol (FA-PEG-VE) were characterized by dynamic light scattering and transmission electron microscopy (TEM).     The mixed micelles had a spherical morphology with an average diameter of 137.0±6.70 nm and a zeta potential of -48.7±4.25 mV.     The drug encapsulation and loading efficiencies were 91.06%±2.45% and 5.28%±0.30%, respectively.     The pH sensitivity was confirmed by changes in particle size, critical micelle concentration, and transmittance as a function of pH. MTT assay showed that PHIS/FA/PM had higher cytotoxicity at pH 6.0 than at pH 7.4, and lower cytotoxicity in the presence of free FA.     Confocal laser scanning microscope images demonstrated a time-dependent and FA-inhibited cellular uptake.     In vivo imaging confirmed that the mixed micelles targeted accumulation at tumor sites and the tumor inhibition rate was 85.97%.     The results proved that the mixed micelle system fabricated by MPEG-PHIS and FA-PEG-VE is a promising approach to improve antitumor efficacy. Keywords: drug delivery;     folic acid targeting;     in vivo antitumor activity;     mixed micelles;     pH sensitive. 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