Acta Biomater. 2019 Mar 1;86:280-290. doi: 10.1016/j.actbio.2019.01.003. Epub 2019 Jan 5. In situ chemically crosslinked injectable hydrogels for the subcutaneous delivery of trastuzumab to treat breast cancer Yu-Wen Lo, Ming-Thau Sheu, Wen-Hsuan Chiang, Ya-Ling Chiu, Chia-Mu Tu, Wen-Yu Wang, Ming-Hsi Wu, Yu-Cheng Wang, Maggie Lu, Hsiu-O Ho Abstract Recently, novel approaches for the delivery of therapeutic antibodies have attracted much attention, especially sustained release formulations. However, sustained release formulations capable of carrying a high antibody load remain a challenge for practical use. In this study, a novel injectable hydrogel composed of maleimide-modified γ-polyglutamic acid (γ-PGA-MA) and thiol end-functionalized 4-arm poly(ethylene glycol) (4-arm PEG-SH) was developed for the subcutaneous delivery of trastuzumab. γ-PGA-MA and 4-arm PEG-SH formed a hydrogel through thiol-maleimide reactions, which had shear-thinning properties and reversible rheological behaviors. Moreover, a high content of trastuzumab (>100 mg/mL) could be loaded into this hydrogel, and trastuzumab demonstrated a sustained release over several weeks through electrostatic attraction. In addition, trastuzumab released from the hydrogel had adequate stability in terms of its structural integrity, binding bioactivity, and antiproliferative effect on BT-474 cells. Pharmacokinetic studies demonstrated that trastuzumab-loaded hydrogel (Her-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, and 10 mg/mL trastuzumab) and trastuzumab/Zn-loaded hydrogel (Her/Zn-hydrogel-10, composed of 1.5% γ-PGA-MA, 1.5% 4-arm PEG-SH, 5 mM ZnCl2, and 10 mg/mL trastuzumab) could lower the maximum plasma concentration (Cmax) than the trastuzumab solution. Furthermore, Her/Zn-hydrogel-10 was better able to release trastuzumab in a controlled manner, which was ascribed to electrostatic attraction and formation of trastuzumab/Zn nanocomplexes. In a BT-474 xenograft tumor model, Her-hydrogel-10 had a similar tumor growth-inhibitory effect as that of the trastuzumab solution. By contrast, Her/Zn-hydrogel-10 exhibited a superior tumor growth-inhibitory capability due to the functionality of Zn. This study demonstrated that this hydrogel has potential as a carrier for the local and systemic delivery of proteins and antibodies. STATEMENT OF SIGNIFICANCE: Recently, novel sustained-release formulations of therapeutic antibodies have attracted much attention. However, these formulations should be able to carry a high antibody load owing to the required high dose, and these formulations remain a challenge for practical use. In this study, a novel injectable chemically cross-linked hydrogel was developed for the subcutaneous delivery of trastuzumab. This novel hydrogel possessed ideal characteristics of loading high content of trastuzumab (>100 mg/mL), sustained release of trastuzumab over several weeks, and maintaining adequate stability of trastuzumab. In vivo studies demonstra...

Biomater Sci. 2017 Mar 28;5(4):730-740. doi: 10.1039/c7bm00042a. Dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy Dan Li, Litao Li, Yunlong Ma, Yaping Zhuang, Dawei Li, Hong Shen, Xing Wang, Fei Yang, Yuanzheng Ma, Decheng Wu Abstract Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment. Related products Abbreviation: 4-arm PEG-OH Name: 4-arm 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

Small. 2019 Apr;15(16):e1900110. doi: 10.1002/smll.201900110. Epub 2019 Mar 26. A Cut-and-Weld Process to 3D Architectures from Multiresponsive Crosslinked Liquid Crystalline Polymers Xiaoxiong Zheng, Song Guan, Chen Zhang, Ting Qu, Wei Wen, Yongbin Zhao, Aihua Chen Abstract Crosslinked liquid crystalline polymers (CLCPs) have garnered extensive attention in recent years for their significant values in the design of light-driven soft actuators. However, poor processabilities due to the insoluble and infusible crosslinked networks prevent their practical applications severely. In this study, a weldable azobenzene-containing CLCP is designed with photo- and humidity-responsive actuations, which enables a cut-and-weld process to 3D CLCP architectures. The tensile properties and stability are almost unchanged after welding, much better than those of the films pasted by common adhesive tapes. Meanwhile, the mechanisms of the welding process are clarified on the base of surface hydrogen bonding and further crosslinking. By taking advantage of the cut-and-weld process, a 3D "claw" integrated into a robotic arm is realized for grabbing millimeter-scale objects by remote control. This work enhances significantly not only the processability of CLCP films but also the utilization of leftover pieces, which provides an efficient approach to create functional 3D structures from film precursors for the potential application in the smart materials. Keywords: azobenzene; cut-and-weld; humidity-responsive; liquid crystalline polymers; photoresponsive. Related products Abbreviation: 4-arm PEG-OH Name: 4-arm 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

ACS Appl Bio Mater. 2019 Jun 17;2(6):2444-2452. doi: 10.1021/acsabm.9b00156. Epub 2019 May 15. Bone Marrow Mesenchymal Stem Cells Encapsulated in a Hydrogel System via Bioorthogonal Chemistry for Liver Regeneration Yajie Zhang, Yue Zan, Hong Chen, Zhili Wang, Tianyu Ni, Min Liu, Renjun Pei Abstract Liver tissue engineering is going to be an effective treatment for end-stage liver disease. In this work, we distributed bone marrow mesenchymal stem cells (BMSCs) into a fast-forming hydrogel system to develop a liver-mimicking construct for liver regeneration. The advantage of this hydrogel system was that this BMSC-encapsulating hydrogel could be formed via a bioorthogonal reaction between 2-cyanobenzothiazole and cysteine within several seconds. Thereafter, we explored the morphology, biocompatibility, and expressions of hepatic differentiation markers of this hydrogel system. These results illustrated that this system could provide a suitable niche for BMSC proliferation and differentiation, which could aid in future biomedical research of liver regeneration. Keywords: BMSC-encapsulating; bioorthogonal reaction; fast-forming hydrogel; liver regeneration; tissue engineering. Related products Abbreviation: 4-arm PEG-NH2 Name: 4-arm Poly(ethylene glycol) amine Abbreviation: 4-arm PEG-CM Name: 4-arm Poly(ethylene glycol) carboxylic acid 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

Colloids Surf B Biointerfaces. 2016 Sep 1;145:785-794. doi: 10.1016/j.colsurfb.2016.05.074. Epub 2016 May 27. Efficient nanobiocatalytic systems of nuclease P1 immobilized on PEG-NH2 modified graphene oxide: effects of interface property heterogeneity Wei Zhuang, Linjiao He, Jiahua Zhu, Jianwei Zheng, Xiaojing Liu, Yihui Dong, Jinglan Wu, Jingwei Zhou, Yong Chen, Hanjie Ying Abstract The use of graphene oxide (GO) nanosheets for functional enzyme support has attracted intensive interest owing to their unique planar structure and intriguing physical and chemical properties. However, the detailed effects of the interface properties of GO and its functionalized derivatives on active biomolecules are not well understood. We immobilize nuclease P1, a common industrial nucleic acid production enzyme, on pristine and amino poly(ethylene glycol) (PEG-NH2) modified GO nanosheets with interface property heterogeneity using two approaches, physical adsorption and chemical crosslinking. It is demonstrated that nuclease P1 could be stable immobilized on the surface of pristine GO by physical adsorption and on the edge of modified GO nanosheets by chemical crosslinking. The resultant loading capacity of nuclease P1 on pristine GO is as high as 6.45mg/mg as a consequence of strong electrostatic and hydrophobic interactions between the enzyme and carrier. However, it is determined that the acid resistance, thermal stability, reusability and degradation efficiency of the immobilized enzyme on PEG-NH2-modified GO are obviously improved compared to those of the enzyme immobilized on pristine GO. The enhanced catalytic behavior demonstrates that GO and its derivatives have great potential in efficient biocatalytic systems. Keywords: Enzyme immobilization; Graphene oxide; Interface; Modification; Nuclease P(1). Related products Abbreviation: 4-arm PEG-NH2 Name: 4-arm Poly (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

ACS Omega. 2018 Feb 28;3(2):2396-2405. doi: 10.1021/acsomega.7b02022. Epub 2018 Feb 27. Combined Adsorption and Covalent Linking of Paclitaxel on Functionalized Nano-Graphene Oxide for Inhibiting Cancer Cells Wei Zhuang, Linjiao He, Kai Wang, Bo Ma, Lei Ge, Zhenfu Wang, Jinsha Huang, Jinglan Wu, Qi Zhang, Hanjie Ying Abstract Developing targeted delivery nanosystems for delivering chemotherapeutic anticancer drugs specifically to cancerous tissues with improvement in the specificity of drugs for different cancer cells can result in high therapeutic efficacy and low toxicity in healthy tissues. Herein, we proposed the synthesis of a multifunctional nanodelivery system, folic acid (FA) decorating nanographene oxide (nGO) functionalized with poly(ethylene glycol) (PEG), called pGO-FA, with good biocompatibility and good delivering performance of a hydrophobic water-insoluble anticancer drug of paclitaxel (PTX). 4-br-PEG-NH2, FA, and PTX were attached to PEG-functionalized nGO (pGO) through a combined chemical and physical force to form a nanosized complex, pGO-FA-PTX, defined as the nanodrug system. WST-8 assay in vitro illustrated that pGO-FA-PTX inhibited A2780 cells in a concentration-dependent manner. Cell viability was kept high to 60% when treated with 200 nM of free PTX. However, pGO-FA-PTX with the same dose of PTX (cell viability less than 30%) had double the cytotoxicity effect compared to free PTX. Furthermore, fluorescence observation demonstrated that pGO-FA-PTX exhibited an improved efficiency in killing A2780 cells due to the special affinity between FA and FA receptor, which has high expression in cancer cells. The strategy and method used in this study could be effective in improving both the bioavailability of PTX and therapy efficiency. Related products Abbreviation: 4-arm PEG-NH2 Name: 4-arm Poly(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

Langmuir. 2020 Feb 11;36(5):1235-1240. doi: 10.1021/acs.langmuir.9b03325. Epub 2020 Jan 27. Host-Guest Interactions between Oxaliplatin and Cucurbit[7]uril/Cucurbit[7]uril Derivatives under Pseudo-Physiological Conditions Han Wu, Hao Chen, Bohan Tang, Yuetong Kang, Jiang-Fei Xu, Xi Zhang Abstract Compared with conventional drug delivery systems (DDSs), DDSs based on host-guest interactions possess unique advantages, such as high selectivity, tunable binding ability, and controllable release of drugs. It is important to study the host-guest interactions between the carrier and drug under physiological conditions for constructing DDSs. In this work, we have studied the host-guest interaction between cucurbit[7]uril (CB[7]) and oxaliplatin (OxPt), a clinical antitumor drug, in the cell culture medium. The results show that amino acids such as phenylalanine in the 1640 culture medium can partially occupy the cavity of CB[7], which leads to the decrease of enthalpy changes of the host-guest interaction between OxPt and CB[7]. In addition, inorganic salts such as NaCl in the medium reduce the enthalpy change and increase the entropy change of the binding because of the preorganization of the portal of CB[7] and sodium cation. As a result, the binding constant of CB[7] with OxPt in the 1640 culture medium is 1/20 of that in pure water. When CB[7] is modified at the terminal of star-type PEG to construct the star-PEGylated CB[7], it is shown that the molecular weight and topological structure of the PEG polymer backbone exhibit little effect on the host-guest interactions between CB[7] and OxPt. This study enriches the host-guest chemistry of cucurbiturils and may provide guidance for constructing novel DDSs based on host-guest interactions with high loading and releasing efficiency. Related products Abbreviation: 2-arm PEG-N3 (PT02) Name: 2-arm Methoxypoly (ethylene glycol) azide (PT02) 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

LNP formulations usually have between 35-45% composition with respect to cholesterol. Cholesterol is a derivative of cyclopentane polyhydrophenanthrene, which is widely present in animals. Cholesterol is involved in the formation of cell membranes and is an indispensable and important substance in animal tissue cells. Traditionally, cholesterol is derived from animals, mainly from the saponification of the brain and vertebral tendons of pigs, cattle and sheep, or lanolin, which is extracted using organic solvents. Since many diseases are now found to be transmitted from animals to humans, according to the latest guidelines for cell therapy and gene therapy, animal-derived ingredients should be avoided and a safer source of cholesterol is needed. SINOPEG's plant-derived cholesterol is synthesized through biosynthesis technology using plant extracts as the initial raw material. The product has no animal origin and meets the guidelines for cell therapy and gene therapy with high safety and clear composition. The product is a pure plant-derived biosynthetic cholesterol with no animal-derived components. It is less risky compared to traditional lanolin, pig, and cow products of animal origin. Plant-derived cholesterol is well suited for applications in the preparation of lipid nanoparticle (LNP) delivery systems, in the development of mRNA vaccines, in cell culture, serum-free cell culture for protein drugs, and other high-technology drug researches. Plant-derived cholesterol can also be used as a key raw material for the synthesis of vitamin D and its derivatives. The typical application includes such as in small unilamellar vesicles’ preparation, in the preparation of small unilamellar vesicles for structured illumination microscopy studies, in the generation of thymoquinone (TQ) loaded liposomes for administering into murine model with Candida albicans infection. Lipids for LNPs DHA (ALC-0315) mPEG-DTA (ALC-0159) HUO (SM-102) mPEG-DMG DSPC DOPE Cholesterol (Plant) R-DODMA R-DOTMA-Cl Dlin-MC3-DMA DOTAP DOTAP-Cl mPEG-DSG mPEG-C-DMG DSPE-PEG-MAL 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