J Control Release. 2020 May 10;321:629-640. doi: 10.1016/j.jconrel.2020.02.049. Epub 2020 Mar 2. Hyperbranched lipoid-based lipid nanoparticles for bidirectional regulation of collagen accumulation in liver fibrosis Jian-Bin Qiao, Qian-Qian Fan, Cheng-Lu Zhang, Jaiwoo Lee, Junho Byun, Lei Xing, Xiang-Dong Gao, Yu-Kyoung Oh, Hu-Lin Jiang Abstract Liver fibrosis leads to over one million deaths annually worldwide. Hepatic stellate cells (HSCs) have been identified as the main executors of liver fibrosis. Unfortunately, no drug has yet been approved for clinical use against liver fibrosis, largely because the tested drugs have been unable to access HSCs and efficiently remove the collagen accumulation involved in fibrogenesis. Here, we designed an efficient HSC-targeting lipid delivery system that carried dual siRNAs intended to both inhibit collagen synthesis and promote collagen degradation, with the goal of realizing enhanced anti-liver fibrosis by bidirectional regulation of collagen accumulation. The delivery system was constructed by using amphiphilic cationic hyperbranched lipoids (C15-PA) for siRNA complexation and helper lipoids (cholesterol-polyethylene glycol-vitamin A, Chol-PEG-VA) for HSCs targeting. The generated vitamin A-decorated and hyperbranched lipoid-based lipid nanoparticles (VLNPs) showed excellent gene-binding ability and transfection efficiency, and enhanced the delivery of siRNAs to HSCs. Fibrotic mice treated with dual siRNA-loaded VLNPs showed a great reduction in the collagen accumulation seen in this model; the enhanced effect of bidirectional regulation reduced the collagen accumulation level in treated mice to almost that seen in normal mice. There was no notable sign of toxicity or tissue inflammation in mice exposed to repeated intravenous administration of the dual siRNA-loaded VLNPs. In conclusion, our results indicate that biocompatible VLNPs designed to exploit precise targeting and an effective bidirectional regulation strategy hold promise for treating liver fibrosis. Keywords: Bidirectional regulation; Collagen accumulation; Hepatic stellate cells; Lipoid-based lipid nanoparticles; Liver fibrosis; siRNA. Related products Abbreviation: HOOC-PEG-COOH Name: α,ω-Dicarboxyl 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 Nano. 2020 Feb 25;14(2):2063-2076. doi: 10.1021/acsnano.9b08667. Epub 2020 Feb 7. Ultrasound-Switchable Nanozyme Augments Sonodynamic Therapy against Multidrug-Resistant Bacterial Infection Duo Sun, Xin Pang, Yi Cheng, Jiang Ming, Sijin Xiang, Chang Zhang, Peng Lv, Chengchao Chu, Xiaolan Chen, Gang Liu, Nanfeng Zheng Abstract Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra(4-carboxyphenyl)porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such "blocking and activating" enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely. Keywords: bacterial infection; multidrug-resistant; nanozyme; sonodynamic therapy; ultrasound-switchable. Related products Abbreviation: H2N-PEG-SH Name: α-Amino-ω-mercapto 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

Nanoscale. 2016 Mar 14;8(10):5706-13. doi: 10.1039/c5nr09120a. Platinum(IV) prodrug conjugated Pd@Au nanoplates for chemotherapy and photothermal therapy Saige Shi, Xiaolan Chen, Jingping Wei, Yizhuan Huang, Jian Weng, Nanfeng Zheng Abstract Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(IV) prodrug c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)2] to obtain a nanocomposite (Pd@Au-PEG-Pt) for combined photothermal-chemotherapy. The prepared Pd@Au-PEG-Pt nanocomposite showed excellent stability in physiological solutions and efficient Pt(IV) prodrug loading. Once injected into biological tissue, the Pt(IV) prodrug was easily reduced by physiological reductants (e.g. ascorbic acid or glutathione) into its cytotoxic and hydrophilic Pt(II) form and released from the original nanocomposite, and the NIR laser irradiation could accelerate the release of Pt(II) species. More importantly, Pd@Au-PEG-Pt has high tumor accumulation (29%ID per g), which makes excellent therapeutic efficiency at relatively low power density possible. The in vivo results suggested that, compared with single therapy the combined thermo-chemotherapy treatment with Pd@Au-PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pd@Au-PEG-Pt without irradiation or photothermal treatment using Pd@Au-PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pd@Au nanoplates as drug delivery carriers for multimode cancer treatment. Related products Abbreviation: H2N-PEG-SH Name: α-Amino-ω-mercapto 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

J Drug Target. 2015;23(6):568-76. doi: 10.3109/1061186X.2015.1018910. Epub 2015 Mar 4. Effective photothermal chemotherapy with docetaxel-loaded gold nanospheres in advanced prostate cancer Yanfang Shen, Zhiya Ma, Fei Chen, Qingjian Dong, Qiran Hu, Lingyu Bai, Jing Chen Abstract Background: Multifunctional gold nanospheres (MGNs)-loaded with docetaxel (MGN@DTX) were prepared and evaluated for therapeutic efficacy in nude mice bearing human prostate cancer xenografts. Methods: MGNs were prepared from PEGylated hollow gold nanospheres (HGNs) coated with folic acid and DTPTT chelate. Then, the effect of radiolabelled MGNs ((99m)Tc-MGNs) on PC-3 cell apoptosis was assessed by flow cytometry, while their binding affinity to these cells was evaluated by cell binding assays. Next, biodistribution of (99m)Tc-MGNs in xenograft bearing mice was measured by SPECT imaging. Also, DTX loading and release rates were estimated in MGN@DTX. Finally, in vitro stability in human serum and cytotoxicity of MGN@DTX were assessed, as well as their antitumor effect in xenograft bearing mice. Results: (99m)Tc-MGNs (97.69% purity) showed good binding affinity to PC-3 cells, a specific recognition blocked by excess folic acid. Interestingly, MGN@DTX remained stable in human serum for 24 h, and exhibited higher mean cytotoxicity after NIR laser irradiation than free DTX. By day 28, tumor inhibition rates were higher in the MGN@DTX + NIR laser irradiation group compared with the DTX and MGNs + NIR laser irradiation groups. Conclusions: Loading chemotherapeutic drugs into MGNs can increase antitumor potency, reduce normal cell damage and decrease drug resistance, thus representing a promising approach for advanced prostate cancer treatment. Keywords: Docetaxel; gold nanospheres; near-infrared laser; prostate cancer. Related products Abbreviation: H2N-PEG-SH Name: α-Amino-ω-mercapto 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

First published: 26 February 2018. https://doi.org/10.1002/adfm.201706310 A Novel Theranostic Nanoplatform Based on Pd@Pt-PEG-Ce6 for Enhanced Photodynamic Therapy by Modulating Tumor Hypoxia Microenvironment Jingping Wei, Jingchao Li, Duo Sun, Qi Li, Jinyuan Ma, Xiaolan Chen, Xuan Zhu, Nanfeng Zheng Abstract Photodynamic therapy (PDT), which utilizes reactive oxygen species to kill cancer cells, has found wide applications in cancer treatment. However, the hypoxic nature of most solid tumors can severely restrict the efficiency of PDT. Meanwhile, the hydrophobicity and limited tumor selectivity of some photosensitizers also reduce their PDT efficacy. Herein, a photosensitizer-Pd@Pt nanosystem (Pd@Pt-PEG-Ce6) is designed for highly efficient PDT by overcoming these limitations. In the nanofabrication, Pd@Pt nanoplates, exhibiting catalase-like activity to decompose H2O2 to generate oxygen, are first modified with bifunctional PEG (SH-PEG-NH2). Then the Pd@Pt-PEG is further covalently conjugated with the photosensitizer chlorin e6 (Ce6) to get Pd@Pt-PEG-Ce6 nanocomposite. The Pd@Pt-PEG-Ce6 exhibits good biocompatibility, long blood circulation half-life, efficient tumor accumulation, and outstanding imaging properties. Both in vitro and in vivo experimental results clearly indicate that Pd@Pt-PEG-Ce6 effectively delivers photosensitizers to cancer cells/tumor sites and triggers the decomposition of endogenous H2O2 to produce oxygen, resulting in a remarkably enhanced PDT efficacy. Moreover, the moderate photothermal effect of Pd@Pt nanoplates also strengthen the PDT of Pd@Pt-PEG-Ce6. Therefore, by integrating the merits of high tumor-specific accumulation, hypoxia modulation function, and mild photothermal effect into a single nanoagent, Pd@Pt-PEG-Ce6 readily acts as an ideal nanotherapeutic platform for enhanced cancer PDT. Related products Abbreviation: H2N-PEG-SH Name: α-Amino-ω-mercapto 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

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