Colloids Surf B Biointerfaces. 2019 Aug 1;180:58-67. doi: 10.1016/j.colsurfb.2019.04.042. Epub 2019 Apr 18. RGD peptide-decorated micelles assembled from polymer-paclitaxel conjugates towards gastric cancer therapy Jingwen Shi, Shuiping Liu, Yuan Yu, Changyu He, Lianjiang Tan, Yu-Mei Shen Abstract Development of polymer-drug conjugate capable of controlled drug release is urgently needed for gastric cancer therapy. Herein, arginine-glycine-aspartic acid (RGD)-decorated polyethylene glycol (PEG)-paclitaxel (PTX) conjugates containing disulfide linkage were synthesized. The amphiphilic PEG-PTX conjugates were found to assemble into micelles (RGD@Micelles), which would be decomposed under the reduction of glutathione (GSH) and finally release PTX in weakly acidic conditions characteristic of intracellular environment. The RGD@Micelles were spherical nanoparticles with an average hydrodynamic size of ˜50 nm, which were stable in physiological environment. The release of PTX from the micelles in response to GSH was investigated. In vitro cell assay suggested that the RGD@Micelles could target the gastric cancer cells and inhibit cell proliferation by inducing apoptosis. In vivo experiments indicated that the RGD@Micelles could be delivered to the tumor site and inhibit the tumor growth efficiently by releasing PTX inside the tumor cells. This type of micelles exhibited high therapeutic efficacy and low side effects, providing new insights into targeted drug delivery for gastric cancer therapy. Keywords: Drug release; Gastric cancer; Polymer-drug conjugates; RGD peptide; Tumor-targeting micelles Related products Abbreviation: H2N-PEG-OH Name: α-Amino-ω-hydroxyl 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

Org Biomol Chem. 2017 Sep 20;15(36):7607-7617. doi: 10.1039/c7ob01352c. Synthetic approach to tailored physical associations in peptide-polyurea/polyurethane hybrids L E Matolyak, J K Keum, K M Van de Voorde, L T J Korley Abstract Nature has achieved diverse functionality via hierarchical organization driven by physical interactions such as hydrogen bonding. Synthetically, polymer-peptide hybrids have been utilized to achieve these architectural arrangements and obtain diverse mechanical properties, stimuli responsiveness, and bioactivity. Here, we explore the impact of peptide ordering and soft/hard phase interactions in PEG-based non-chain extended and chain extended peptidic polyurea (PU) and polyurea/polyurethane (PUU) hybrids towards tunable mechanics. Increasing the peptide content of poly(ε-carbobenzyloxy-l-lysine) (PZLY) revealed an increase in α-helical formation and modulation in amine/ether hydrogen bonding, suggesting enhanced intermolecular hydrogen bonding between peptide segments and soft/hard blocks. A balance of phase mixing and microphase segregation was observed depending on competitive hydrogen bonding and the hybrid architecture. This phase behaviour strongly modulated the mechanical response, particularly modulus and extensibility. We anticipate that this solid-state, synthetic framework will expand the reach of our peptide hybrids into biointerfacing materials, including scaffolds and responsive actuators via peptide selection. Related products Abbreviation: H2N-PEG-NH2 Name: α,ω-Diamino 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

Biomacromolecules. 2018 Aug 13;19(8):3445-3455. doi: 10.1021/acs.biomac.8b00762. Epub 2018 Jul 12. Secondary-Structure-Mediated Hierarchy and Mechanics in Polyurea-Peptide Hybrids Lindsay E Matolyak, Chase B Thompson, Bingrui Li, Jong K Keum, Jonathan E Cowen, Richard S Tomazin, LaShanda T J Korley Abstract Peptide-polymer hybrids combine the hierarchy of biological species with synthetic concepts to achieve control over molecular design and material properties. By further incorporating covalent cross-links, the enhancement of molecular complexity is achieved, allowing for both a physical and covalent network. In this work, the structure and function of poly(ethylene glycol) (PEG)-network hybrids are tuned by varying peptide block length and overall peptide content. Here the impact of poly(ε-carbobenzyloxy-l-lysine) (PZLY) units on block interactions and mechanics is explored by probing secondary structure, PEG crystallinity, and hierarchical organization. The incorporation of PZLY reveals a mixture of α-helices and β-sheets at smaller repeat lengths ( n = 5) and selective α-helix formation at a higher peptide molecular weight ( n = 20). Secondary structure variations tailored the solid-state film hierarchy, whereby nanoscale fibers and microscale spherulites varied in size depending on the amount of α-helices and β-sheets. This long-range ordering influenced mechanical properties, resulting in a decrease in elongation-at-break (from 400 to 20%) with increasing spherulite diameter. Furthermore, the reduction in soft segment crystallinity with the addition of PZLY resulted in a decrease in moduli. It was determined that, by controlling PZLY content, a balance of physical associations and self-assembly is obtained, leading to tunable PEG crystallinity, spherulite formation, and mechanics. Related products Abbreviation: H2N-PEG-NH2 Name: α,ω-Diamino 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

Mol Pharm. 2015 Mar 2;12(3):769-82. doi: 10.1021/mp5006068. Epub 2015 Feb 5. Orthogonally functionalized nanoscale micelles for active targeted codelivery of methotrexate and mitomycin C with synergistic anticancer effect Yang Li, Jinyan Lin, Hongjie Wu, Ying Chang, Conghui Yuan, Cheng Liu, Shuang Wang, Zhenqing Hou, Lizong Dai Abstract The design of nanoscale drug delivery systems for the targeted codelivery of multiple therapeutic drugs still remains a formidable challenge (ACS Nano, 2013, 7, 9558-9570; ACS Nano, 2013, 7, 9518-9525). In this article, both mitomycin C (MMC) and methotrexate (MTX) loaded DSPE-PEG micelles (MTX-M-MMC) were prepared by self-assembly using the dialysis technique, in which MMC-soybean phosphatidylcholine complex (drug-phospholipid complex) was encapsulated within MTX-functionalized DSPE-PEG micelles. MTX-M-MMC could coordinate an early phase active targeting effect with a late-phase synergistic anticancer effect and enable a multiple-responsive controlled release of both drugs (MMC was released in a pH-dependent pattern, while MTX was released in a protease-dependent pattern). Furthermore, MTX-M-MMC could codeliver both drugs to significantly enhance the cellular uptake, intracellular delivery, cytotoxicity, and apoptosis in vitro and improve the tumor accumulation and penetration and anticancer effect in vivo compared with either both free drugs treatment or individual free drug treatment. To our knowledge, this work provided the first example of the systemically administrated, orthogonally functionalized, and self-assisted nanoscale micelles for targeted combination cancer chemotherapy. The highly convergent therapeutic strategy opened the door to more simplified, efficient, and flexible nanoscale drug delivery systems. Keywords: combination cancer chemotherapy; methotrexate; micelles; mitomycin C; targeted drug delivery Related products Abbreviation: H2N-PEG-NH2 Name: α,ω-Diamino 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 Mater Interfaces. 2015 May 27;7(20):11015-23. doi: 10.1021/acsami.5b02803. Epub 2015 May 13. Multifunctional Poly(L-lactide)-Polyethylene Glycol-Grafted Graphene Quantum Dots for Intracellular MicroRNA Imaging and Combined Specific-Gene-Targeting Agents Delivery for Improved Therapeutics Haifeng Dong, Wenhao Dai, Huangxian Ju, Huiting Lu, Shiyan Wang, Liping Xu, Shu-Feng Zhou, Yue Zhang, Xueji Zhang Abstract Photoluminescent (PL) graphene quantum dots (GQDs) with large surface area and superior mechanical flexibility exhibit fascinating optical and electronic properties and possess great promising applications in biomedical engineering. Here, a multifunctional nanocomposite of poly(l-lactide) (PLA) and polyethylene glycol (PEG)-grafted GQDs (f-GQDs) was proposed for simultaneous intracellular microRNAs (miRNAs) imaging analysis and combined gene delivery for enhanced therapeutic efficiency. The functionalization of GQDs with PEG and PLA imparts the nanocomposite with super physiological stability and stable photoluminescence over a broad pH range, which is vital for cell imaging. Cell experiments demonstrate the f-GQDs excellent biocompatibility, lower cytotoxicity, and protective properties. Using the HeLa cell as a model, we found the f-GQDs effectively delivered a miRNA probe for intracellular miRNA imaging analysis and regulation. Notably, the large surface of GQDs was capable of simultaneous adsorption of agents targeting miRNA-21 and survivin, respectively. The combined conjugation of miRNA-21-targeting and survivin-targeting agents induced better inhibition of cancer cell growth and more apoptosis of cancer cells, compared with conjugation of agents targeting miRNA-21 or survivin alone. These findings highlight the promise of the highly versatile multifunctional nanocomposite in biomedical application of intracellular molecules analysis and clinical gene therapeutics. Keywords: cell imaging; gene therapeutics; graphene quantum dots; microRNAs; survivin. Related products Abbreviation: H2N-PEG-NH2 Name: α,ω-Diamino 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

Biomaterials. 2015 Aug; 61:178-89. doi: 10.1016/j.biomaterials.2015.05.027. Epub 2015 May 16. Mitochondria apoptosis pathway synergistically activated by hierarchical targeted nanoparticles co-delivering siRNA and lonidamine Bing-Feng Zhang, Lei Xing, Peng-Fei Cui, Feng-Zhen Wang, Rong-Lin Xie, Jia-Liang Zhang, Mei Zhang, Yu-Jing He, Jin-Yuan Lyu, Jian-Bin Qiao, Bao-An Chen, Hu-Lin Jiang Abstract The mitochondria-mediated apoptosis pathway is an effective option for cancer therapy due to the presence of cell-suicide weapons in mitochondria. However, anti-apoptotic proteins that are over-expressed in the mitochondria of many malignant tumors, such as Bcl-2 protein, could allow the cancer cells to evade apoptosis, greatly reducing the efficacy of this type of chemotherapy. Here, we constructed a hierarchical targeted delivery system that can deliver siRNA and chemotherapeutic agents sequentially to tumor cells and mitochondria. In detail, the copolymer TPP-CP-LND (TCPL) was synthesized by the mitochondria-targeting ligand triphenylphosphine (TPP) and therapeutic drug lonidamine (LND) conjugated to the polyethyleneimine in chitosan-graft-PEI (CP), and then complexed with siRNA. Followed, the complexes were coated with poly(acrylic acid)-polyethylene glycol-folic acid (PPF) copolymer to form a hierarchical targeted co-delivery system (TCPL/siRNA/PPF NPs). The TCPL/siRNA/PPF NPs had a neutral surface charge, were stable in plasma and exhibited pH-responsive shell separation. Remarkably, the TCPL/siRNA/PPF NPs simultaneously released siBcl-2 into the cytoplasm and delivered LND to mitochondria in the same cancer cell after FA-directed internalization, and even synergistically activated mitochondria apoptosis pathway. This work demonstrated the potential of RNA-interference and mitochondria-targeted chemotherapeutics to collaboratively stimulate the mitochondria apoptosis pathway for cancer therapy. Keywords: Co-delivery; Hierarchical targeting; Lonidamine; Mitochondria apoptosis pathway; Multifunctional nanoparticle; siRNA. Related products Abbreviation: H2N-PEG-NH2 Name: α,ω-Diamino 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

Biomacromolecules. 2017 Jan 9;18(1):150-158. doi: 10.1021/acs.biomac.6b01437. Epub 2016 Dec 2. Poly(glycerol) Used for Constructing Mixed Polymeric Micelles as T1 MRI Contrast Agent for Tumor-Targeted Imaging Yi Cao, Min Liu, Kunchi Zhang, Guangyue Zu, Ye Kuang, Xiaoyan Tong, Dangsheng Xiong, Renjun Pei Abstract There was much interest in the development of nanoscale delivery vehicles based on polymeric micelles to realize the diagnostic and therapeutic applications in biomedicine. Here, with the purpose of constructing a micellar magnetic resonance imaging (MRI) contrast agent (CA) with well biocompatibility and targeting specificity, two types of amphiphilic diblock polymers, mPEG-PG(DOTA(Gd))-b-PCL and FA-PEG-b-PCL, were synthesized to form mixed micelles by coassembly. The nanostructure of the resulting micellar system consisted of poly(caprolactone) (PCL) as core and poly(glycerol) (PG) and poly(ethylene glycol) (PEG) as shell, simultaneously modified with DOTA(Gd) chelates and folic acid (FA), which afforded functions of MRI contrast enhancement and tumor targeting. The mixed micelles in aqueous solution presented a hydrodynamic diameter of about 85 nm. Additionally, this mixed micelles exhibited higher r1 relaxivity (14.01 mM-1 S1-) compared with commercial Magnevist (3.95 mM-1 S1-) and showed negligible cytotoxicity estimated by WST assay. In vitro and in vivo MRI experiments revealed excellent targeting specificity to tumor cells and tissue. Furthermore, considerably enhanced signal intensity and prominent positive contrast effect were achieved at tumor region after tumor-bearing mice were intravenously injected with the mixed micelles. These preliminary results indicated the potential of the mixed micelle as T1 MRI CA for tumor-targeted imaging. Related products Abbreviation: Alkyne-PEG-OH Name: α-Alkynyl-ω-hydroxyl 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 Mater Interfaces. 2017 Jul 26;9(29):24511-24517. doi: 10.1021/acsami.7b07204. Epub 2017 Jul 14. Dynamic Softening or Stiffening a Supramolecular Hydrogel by Ultraviolet or Near-Infrared Light Zhao Zheng, Jingjing Hu, Hui Wang, Junlin Huang, Yihua Yu, Qiang Zhang, Yiyun Cheng Abstract The development of light-responsive hydrogels that exhibit switchable size and mechanical properties with temporal and spatial resolution is of great importance in many fields. However, it remains challenging to prepare smart hydrogels that dramatically change their properties in response to both ultraviolet (UV) and near-infrared (NIR) lights. Here, we designed a dual-light responsive supramolecular gel by integrating UV light-switchable host-guest recognition, temperature responsiveness, and NIR photothermal ability in the gel. The gel could rapidly self-heal and is capable of both softening and stiffening controlled by UV and NIR lights, respectively. Besides stiffness modulation, the bending direction of the gel can be controlled by UV or NIR light irradiation. The smart gel makes it possible to generate dynamic materials that respond to both UV and NIR lights and represents a useful tool that might be used to modulate cellular microenvironments with spatiotemporal resolution. Keywords: host−guest interaction; light responsive; self-healing; smart hydrogel; stiffness. Related products Abbreviation: AA-PEG-AA Name: α,ω-Diacryloyl 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