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

Sci Adv. 2020 Jun 17;6(25):eaba2187. doi: 10.1126/sciadv.aba2187. Print 2020 Jun. LiQD Cornea: Pro-regeneration collagen mimetics as patches and alternatives to corneal transplantation Christopher D McTiernan, Fiona C Simpson, Michel Haagdorens, Chameen Samarawickrama, Damien Hunter, Oleksiy Buznyk, Per Fagerholm, Monika K Ljunggren, Philip Lewis, Isabel Pintelon, David Olsen, Elle Edin, Marc Groleau, Bruce D Allan, May Griffith Abstract Transplantation with donor corneas is the mainstay for treating corneal blindness, but a severe worldwide shortage necessitates the development of other treatment options. Corneal perforation from infection or inflammation is sealed with cyanoacrylate glue. However, the resulting cytotoxicity requires transplantation. LiQD Cornea is an alternative to conventional corneal transplantation and sealants. It is a cell-free, liquid hydrogel matrix for corneal regeneration, comprising short collagen-like peptides conjugated with polyethylene glycol and mixed with fibrinogen to promote adhesion within tissue defects. Gelation occurs spontaneously at body temperature within 5 min. Light exposure is not required-particularly advantageous because patients with corneal inflammation are typically photophobic. The self-assembling, fully defined, synthetic collagen analog is much less costly than human recombinant collagen and reduces the risk of immune rejection associated with xenogeneic materials. In situ gelation potentially allows for clinical application in outpatient clinics instead of operating theaters, maximizing practicality, and minimizing health care costs. Related products Abbreviation: 8-arm PEG-MAL Name: 8-arm Poly (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

Biomaterials. 2020 May;240:119841. doi: 10.1016/j.biomaterials.2020.119841. Epub 2020 Feb 6. A well defect-suitable and high-strength biomimetic squid type II gelatin hydrogel promoted in situ costal cartilage regeneration via dynamic immunomodulation and direct induction manners Meilu Dai, Baiyan Sui, Yujie Hua, Yiqing Zhang, Bingkun Bao, Qiuning Lin, Xin Liu, Linyong Zhu, Jiao Sun Abstract Reconstructing segmental costal cartilage defects resulting from autologous cartilage grafts in plastic surgery remains a challenge. The present study focused on a biomimetic strategy for in situ costal cartilage regeneration that did not rely on an autogenous/xenogenous tissue graft. A multifunctional biomimetic SGII/HA-DN hydrogel based on a "chemical-curing, shaping, and light-curing" gelation system was developed and evaluated for its mechanical properties, clinical applications and biological functions. This hydrogel showed good suitability to repair defects and a high mechanical support strength (11 MPa, which is close to the natural strength of costal cartilage). Biologically, the hydrogel exhibited dual-immunomodulatory effects on the pro-inflammatory/anti-inflammatory phenotypes of neutrophils and M1/M2 macrophage polarization and subsequently promoted the chondrogenesis of cartilage stem/progenitor cells through both direct induction and indirect stimulation by the M2 macrophage-mediated TGF-β/Smad pathway. Furthermore, this SGII/HA-DN hydrogel could regulate the local microenvironment, inducing new costal cartilage regeneration in vivo. Our findings demonstrate that the newly developed multifunctional SGII/HA-DN hydrogel provides a strategy with high prospect for the biomimetic repair of segmental costal cartilage defects in clinical practice. Keywords: Costal cartilage regeneration; Double network hydrogel; Dynamic immunomodulation; Macrophage; Neutrophil; Squid type II gelatin. Related products Abbreviation: 4-arm PEG-SS Name: 4-arm Poly(ethylene glycol) succinimidyl succinate 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 Chemistry. Volume 11, Issue 17, 7 May 2020. https://doi.org/10.1039/c9py01503e Two-stage thiol-based click reactions for the preparation and adhesion of hydrogels Wen Jing Yang, Wenya Xu, Xi Tao, Wen Wang, Yaqin Hu, Xue Li, En-Tang Kang, Lianhui Wang Abstract The fabrication of adhesive hydrogel systems is quite important for biological applications. Herein, two-stage thiol-based click reactions have been employed for the preparation and adhesion of hydrogels. In the first stage, two self-adhesive hydrogels (HG-1 and HG-2) were constructed via the thiol-based click reactions and thiol–thiol coupling reaction under different stimuli, employing the same functional copolymer poly(propargyl methacrylate-co-N-(3,4-dihydroxyphenethyl) methacrylamide-co-poly(ethylene glycol) methyl ether methacrylate) (poly(PMA-co-DMA-co-PEGMA), polyPDP) and a 4-arm thiol-PEG cross-linker. Subsequently, the two prepared hydrogels achieved responsive self-adhesion properties via the second stage of thiol-based click reactions between the preserved functional groups under different stimuli. Moreover, the self-adhered hydrogels exhibited increased mechanical strength after adhesion. The present strategy thus provides a facile approach for the fabrication of hydrogel systems with on-demand self-adhesive properties. Related products Abbreviation: 4-arm PEG-SH Name: 4-arm Poly(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