Published: 08 June 2016 Layered double hydroxide modified by PEGylated hyaluronic acid as a hybrid nanocarrier for targeted drug delivery Anjie Dong  (董岸杰), Xue Li  (李 雪), Weiwei Wang  (王伟伟), Shangcong Han  (韩尚聪), Jianfeng Liu  (刘鉴锋), Jinjian Liu  (刘金剑), Junqiang Zhao  (赵军强), Shuxin Xu  (许舒欣) & Liandong Deng  (邓联东) Transactions of Tianjin University volume 22, pages237–246 (2016) Abstract In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5- FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of pHdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed pH-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments. 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

Theranostics. 2017 Apr 10;7(6):1735-1748. doi: 10.7150/thno.18352. eCollection 2017. Elongated Nanoparticle Aggregates in Cancer Cells for Mechanical Destruction with Low Frequency Rotating Magnetic Field Yajing Shen, Congyu Wu, Taro Q P Uyeda, Gustavo R Plaza, Bin Liu, Yu Han, Maciej S Lesniak, Yu Cheng Abstract Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells. Keywords: Brain cancer cells; Functionalized magnetic nanoparticles; Lysosome damage; Magneto-mechanical actuation; Plasma membrane damage. 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 Jan 25;12:855-869. doi: 10.2147/IJN.S122678. eCollection 2017. Curcumin-coordinated nanoparticles with improved stability for reactive oxygen species-responsive drug delivery in lung cancer therapy Cheng-Qiong Luo, Lei Xing, Peng-Fei Cui, Jian-Bin Qiao, Yu-Jing He, Bao-An Chen, Liang Jin, Hu-Lin Jiang Abstract Background: The natural compound curcumin (Cur) can regulate growth inhibition and apoptosis in various cancer cell lines, although its clinical applications are restricted by extreme water insolubility and instability. To overcome these hurdles, we fabricated a Cur-coordinated reactive oxygen species (ROS)-responsive nanoparticle using the interaction between boronic acid and Cur. Materials and methods: We synthesized a highly biocompatible 4-(hydroxymethyl) phenylboronic acid (HPBA)-modified poly(ethylene glycol) (PEG)-grafted poly(acrylic acid) polymer (PPH) and fabricated a Cur-coordinated ROS-responsive nanoparticle (denoted by PPHC) based on the interaction between boronic acid and Cur. The mean diameter of the Cur-coordinated PPHC nanoparticle was 163.8 nm and its zeta potential was -0.31 mV. The Cur-coordinated PPHC nanoparticle improved Cur stability in physiological environment and could timely release Cur in response to hydrogen peroxide (H2O2). PPHC nanoparticles demonstrated potent antiproliferative effect in vitro in A549 cancer cells. Furthermore, the viability of cells treated with PPHC nanoparticles was significantly increased in the presence of N-acetyl-cysteine (NAC), which blocks Cur release through ROS inhibition. Simultaneously, the ROS level measured in A549 cells after incubation with PPHC nanoparticles exhibited an obvious downregulation, which further proved that ROS depression indeed influenced the therapeutic effect of Cur in PPHC nanoparticles. Moreover, pretreatment with phosphate-buffered saline (PBS) significantly impaired the cytotoxic effect of Cur in A549 cells in vitro while causing less damage to the activity of Cur in PPHC nanoparticle. Conclusion: The Cur-coordinated nanoparticles developed in this study improved Cur stability, which could further release Cur in a ROS-dependent manner in cancer cells. Keywords: coordination; curcumin; hydrogen peroxide; phenylboronic acid; stimuli-responsive. 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

Biomed Pharmacother. 2017 Apr;88:374-383. doi: 10.1016/j.biopha.2016.12.138. Epub 2017 Jan 22. Co-delivery of docetaxel and curcumin prodrug via dual-targeted nanoparticles with synergistic antitumor activity against prostate cancer Jieke Yan, Yuzhen Wang, Yuxiu Jia, Shuangde Liu, Chuan Tian, Wengu Pan, Xiaoli Liu, Hongwei Wang Abstract Purpose: Combination therapy is increasingly used as a primary cancer treatment regimen. In this report, we designed EGFR peptide decorated nanoparticles (NPs) to co-deliver docetaxel (DTX) and pH sensitive curcumin (CUR) prodrug for the treatment of prostate cancer. Results: EGFR peptide (GE11) targeted, pH sensitive, DTX and CUR prodrug NPs (GE11-DTX-CUR NPs) had an average diameter of 167nm and a zeta potential of -37.5mV. The particle size of the NPs was adequately maintained in serum and a sustained drug release pattern was observed. Improved inhibition of cancer cell and tumor tissue growth was shown in the GE11-DTX-CUR NPs group compared to the other groups. Conclusion: It can be summarized that DTX and CUR prodrug could be delivered into tumor cells simultaneously by the GE 11 targeting and the EPR effect of NPs. The resulting GE11-DTX-CUR NPs is a promising system for the synergistic antitumor treatment of prostate cancer. Keywords: Dual-targeted nanoparticles; EGFR-mediated endocytosis; Prostate cancer; Synergistic combination therapy; Targeted delivery system. 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

Nanoscale. 2018 Mar 1;10(9):4432-4441. doi: 10.1039/c7nr06874c. An upconversion nanoplatform with extracellular pH-driven tumor-targeting ability for improved photodynamic therapy Fujin Ai, Na Wang, Xiaoman Zhang, Tianying Sun, Qi Zhu, Wei Kong, Feng Wang, Guangyu Zhu Abstract Upconversion nanoparticles (UCNPs) are widely utilized for photodynamic therapy (PDT) due to their specific upconverting luminescence that utilizes near infrared (NIR) light to excite photosensitizers (PSs) for PDT. The efficiency of UCNP-based PDT will be improved if the cancer-targeting property of nanomedicine is enhanced. Herein, we employed the pH low insertion peptide (pHLIP), a cancer-targeting moiety, to functionalize an 808 nm excited UCNP-based nanoplatform that has a minimized over-heating effect to perform PDT. pHLIP can bring cargo specifically into cancer cells under an acidic environment, realizing the effective active-targeting abilities to cancer cells or tumor due to acidosis. The pHLIP-functionalized nanoplatform was assembled and well characterized. The nanoplatform shows an efficient NIR-irradiated PDT effect in cancer cells, especially under a slightly acidic condition that mimics the tumor microenvironment, and this effectiveness is attributed to the targeting properties of pHLIP to cancer cells under acidic conditions that favor the entry of the nanoplatform. Furthermore, the pHLIP-functionalized nanoplatform shows a favorable safety profile in mice with a high maximum tolerated dose (MTD), which may broaden the availability of administration in vivo. The efficient in vivo antitumor activity is achieved through intratumor injection of the nanoplatform followed by NIR irradiation on the breast tumor. The nanoparticles are largely accumulated in the tumor site, revealing the excellent tumor-targeting properties of the pHLIP-functionalized nanoplatform, which ensures efficient PDT in vivo. Moreover, the nanoparticles have a long retention time in the bloodstream, indicating their stability in vivo. Overall, we provide an example of a UCNP-based nanosystem with tumor-targeting properties to perform efficient PDT both in vitro and in vivo. 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

Polymer, Volume 186, 9 January 2020, 122055 https://doi.org/10.1016/j.polymer.2019.122055 Fluorinated polyhedral oligomeric silsesquioxanes end-capped poly(ethylene oxide) giant surfactants: precise synthesis and interfacial behaviors Xian Xu , Yu Shao , Weijie Wang, Liping Zhu, Hao Liu, Shuguang Yang Abstract Interfacial behavior of giant surfactants with precisely tethered molecular nanoparticles (MNPs) is an important topic. In this article, by the combination of hydrosilylation, esterification, and CuAAC ‘‘click’’ chemistry, poly(ethylene oxide) (PEO) chains were end-capped with particle-like aryl-trifluorovinyl ether functionalized polyhedral oligomeric silsesquioxane (FVPOSS) to construct “one-head one-tail” and “bola-form” giant surfactants. The giant surfactants are spread at air/water interface, and surface pressure-area (π-A) isotherms reveal their interfacial behaviors under compression. Atomic force microscope (AFM) images indicate that the giant surfactants show fractal growth behavior after transferred to the silicon substrate at different surface pressure through the procedure of Langmuir-Blodgett (LB) film deposition. The results are useful for understanding the assembly of giant surfactants at the interface and developing of nanostructured functional materials. Related products Abbreviation: mPEG-N3 Name: Methoxypoly(ethylene glycol) azide Abbreviation: N3-PEG-N3 Name: α,ω-Diazido poly(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

Bioconjug Chem. 2017 Aug 16;28(8):2180-2189. doi: 10.1021/acs.bioconjchem.7b00327. Epub 2017 Aug 1. Optimizing Multistep Delivery of PEGylated Tumor-Necrosis-Factor-Related Apoptosis-Inducing Ligand-Toxin Conjugates for Improved Antitumor Xiaoyue Wei, Xiaoyue Yang, Wenbin Zhao, Yingchun Xu, Liqiang Pan, Shuqing Chen Abstract Although TRAIL (tumor-necrosis-factor (TNF)-related apoptosis-inducing ligand) has been considered a promising broad-spectrum antitumor agent, its further application was limited by poor drug delivery and TRAIL-resistant tumors. A three-step drug delivery strategy was applied to TRAIL for solving these two obstacles in the form of PEG-TRAIL-MMAE (Monomethyl Auristatin E). PEGylation of TRAIL in the first step was carried out to improve its in vivo pharmacokinetics, while the interaction between TRAIL conjugates with death receptors in the second step was designed to activate the TRAIL extrinsic apoptosis pathway, and the further release of MMAE from the lysosome was the third step for introducing another apoptosis pathway to overcome TRAIL resistance in some tumors. Herein, in order to reach a balance among the three steps, the PEG/MMAE ratio was optimized for PEG-TRAIL-MMAE conjugates. PEG-TRAIL-MMAE conjugates with various PEG/MMAE ratios were prepared and compared with each other regarding their pharmacokinetics (PK) and pharmacodynamics (PD). As a result, PEG-TRAIL-MMAE conjugates with a PEG/MMAE ratio of 1:2 showed prolonged half-life in rats (6.8 h), and the best antitumor activity in vitro (IC50 0.31 nM) and in vivo while no sign of toxicity in xenograft models, suggesting it as a promising multistep drug delivery and antitumor strategy after optimization. Related products 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

The 2nd LNP Formulation & Process Development Summit is returning to Boston to welcome 350+ LNP experts for sharing, learning and networking to turbocharge next generation of LNP development. Welcome to visit SINOPEG at booth no.27. 2nd LNP Formulation & Process Development Summit | April 2023 (lnp-formulation-process-development-pharma.com) #event #Boston Xiamen Sinopeg Biotech Co., Ltd. is dedicated to drug delivery systems and related medical device business, focusing on the research, development, production and sales of high-end drug delivery carriers/auxiliary materials/APIs, medical materials, including but not limited to polyethylene glycol derivatives, lipid products, blood sugar control drug modifiers, block copolymers, ADC/ProTAC linkers, biodegradable polymers, exosomes, viral-like particles, as well as providing CDMO and solution services. These products are widely used in long-acting protein/peptide drugs, COVID-19 mRNA vaccines, small nucleic acid drugs, blood sugar control drugs, macromolecular micelle drugs, liposome drugs, gene therapy drugs, immunosuppressants, ADC drugs, ProTAC drugs, medical hydrogels, and other fields, placing the company in a leading position in the industry.