@misc{yang_lu_bomba_gu_2019, title={Cysteine-rich Proteins for Drug Delivery and Diagnosis}, volume={26}, ISSN={["1875-533X"]}, DOI={10.2174/0929867324666170920163156}, abstractNote={An emerging focus in nanomedicine is the exploration of multifunctional nanocomposite materials that integrate stimuli-responsive, therapeutic, and/or diagnostic functions. In this effort, cysteine-rich proteins have drawn considerable attention as a versatile platform due to their good biodegradability, biocompatibility, and ease of chemical modification. This review surveys cysteine-rich protein-based biomedical materials, including protein-metal nanohybrids, gold nanoparticle-protein agglomerates, protein-based nanoparticles, and hydrogels, with an emphasis on their preparation methods, especially those based on the cysteine residue-related reactions. Their applications in tumor-targeted drug delivery and diagnostics are highlighted.}, number={8}, journal={CURRENT MEDICINAL CHEMISTRY}, author={Yang, Guang and Lu, Yue and Bomba, Hunter N. and Gu, Zhen}, year={2019}, pages={1377–1388} } @misc{lu_aimetti_langer_gu_2017, title={Bioresponsive materials}, volume={2}, ISSN={["2058-8437"]}, DOI={10.1038/natrevmats.2016.75}, number={1}, journal={NATURE REVIEWS MATERIALS}, author={Lu, Yue and Aimetti, Alex A. and Langer, Robert and Gu, Zhen}, year={2017}, month={Jan} } @article{lu_lin_chen_hu_liu_yu_gao_dickey_gu_2017, title={Enhanced Endosomal Escape by Light-Fueled Liquid-Metal Transformer}, volume={17}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.6b04346}, abstractNote={Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal. When coated with graphene quantum dots (GQDs), the resulting nanospheres demonstrate the ability to absorb and convert photoenergy to drive the simultaneous phase separation and morphological transformation of the inner liquid-metal core. The morphological transformation from nanospheres to hollow nanorods with a remarkable change of aspect ratio can physically disrupt the endosomal membrane to promote endosomal escape of payloads. This metal-based nanotransformer equipped with GQDs provides a new strategy for facilitating effective endosomal escape to achieve spatiotemporally controlled drug delivery with enhanced efficacy.}, number={4}, journal={NANO LETTERS}, publisher={American Chemical Society (ACS)}, author={Lu, Yue and Lin, Yiliang and Chen, Zhaowei and Hu, Quanyin and Liu, Yang and Yu, Shuangjiang and Gao, Wei and Dickey, Michael D. and Gu, Zhen}, year={2017}, month={Apr}, pages={2138–2145} } @article{hu_yu_qian_lu_kahkoska_xie_jing_buse_gu_2017, title={H2O2-Responsive Vesicles Integrated with Transcutaneous Patches for Glucose-Mediated Insulin Delivery}, volume={11}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.6b06892}, abstractNote={A self-regulated "smart" insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates H2O2-responsive polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia.}, number={1}, journal={ACS NANO}, author={Hu, Xiuli and Yu, Jicheng and Qian, Chenggen and Lu, Yue and Kahkoska, Anna R. and Xie, Zhigang and Jing, Xiabin and Buse, John B. and Gu, Zhen}, year={2017}, month={Jan}, pages={613–620} } @article{lu_gu_2017, title={KIDNEY PHYSIOLOGYA size bandpass filter}, volume={12}, ISSN={["1748-3395"]}, DOI={10.1038/nnano.2017.200}, number={11}, journal={NATURE NANOTECHNOLOGY}, author={Lu, Yue and Gu, Zhen}, year={2017}, month={Nov}, pages={1023–1025} } @article{qian_chen_zhu_yu_zhang_feng_tang_hu_sun_lu_et al._2016, title={ATP-Responsive and Near-Infrared-Emissive Nanocarriers for Anticancer Drug Delivery and Real-Time Imaging}, volume={6}, ISSN={["1838-7640"]}, DOI={10.7150/thno.14843}, abstractNote={Stimuli-responsive and imaging-guided drug delivery systems hold vast promise for enhancement of therapeutic efficacy. Here we report an adenosine-5'-triphosphate (ATP)-responsive and near-infrared (NIR)-emissive conjugated polymer-based nanocarrier for the controlled release of anticancer drugs and real-time imaging. We demonstrate that the conjugated polymeric nanocarriers functionalized with phenylboronic acid tags on surface as binding sites for ATP could be converted to the water-soluble conjugated polyelectrolytes in an ATP-rich environment, which promotes the disassembly of the drug carrier and subsequent release of the cargo. In vivo studies validate that this formulation exhibits promising capability for inhibition of tumor growth. We also evaluate the metabolism process by monitoring the fluorescence signal of the conjugated polymer through the in vivo NIR imaging.}, number={7}, journal={THERANOSTICS}, author={Qian, Chenggen and Chen, Yulei and Zhu, Sha and Yu, Jicheng and Zhang, Lei and Feng, Peijian and Tang, Xin and Hu, Quanyin and Sun, Wujin and Lu, Yue and et al.}, year={2016}, pages={1053–1064} } @article{hu_sun_lu_bomba_ye_jiang_isaacson_gu_2016, title={Tumor Microenvironment-Mediated Construction and Deconstruction of Extracellular Drug-Delivery Depots}, volume={16}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.5b04343}, abstractNote={Protein therapy has been considered the most direct and safe approach to treat cancer. Targeting delivery of extracellularly active protein without internalization barriers, such as membrane permeation and endosome escape, is efficient and holds vast promise for anticancer treatment. Herein, we describe a "transformable" core-shell based nanocarrier (designated CS-NG), which can enzymatically assemble into microsized extracellular depots at the tumor site with assistance of hyaluronidase (HAase), an overexpressed enzyme at the tumor microenvironment. Equipped with an acid-degradable modality, the resulting CS-NG can substantially release combinational anticancer drugs-tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and antiangiogenic cilengitide toward the membrane of cancer cells and endothelial cells at the acidic tumor microenvironment, respectively. Enhanced cytotoxicity on MDA-MB-231 cells and improved antitumor efficacy were observed using CS-NG, which was attributed to the inhibition of cellular internalization and prolonged retention time in vivo.}, number={2}, journal={NANO LETTERS}, author={Hu, Quanyin and Sun, Wujin and Lu, Yue and Bomba, Hunter N. and Ye, Yanqi and Jiang, Tianyue and Isaacson, Ari J. and Gu, Zhen}, year={2016}, month={Feb}, pages={1118–1126} } @article{pacardo_neupane_rikard_lu_mo_mishra_tracy_wang_ligler_gu_2015, title={A dual wavelength-activatable gold nanorod complex for synergistic cancer treatment}, volume={7}, ISSN={["2040-3372"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000357805700034&KeyUID=WOS:000357805700034}, DOI={10.1039/c5nr01568e}, abstractNote={A multifunctional gold nanorod complex was formulated for synergistic anticancer treatment upon ultraviolet (UV) and infrared (IR) light dual irradiations.}, number={28}, journal={NANOSCALE}, author={Pacardo, Dennis B. and Neupane, Bhanu and Rikard, S. Michaela and Lu, Yue and Mo, Ran and Mishra, Sumeet R. and Tracy, Joseph B. and Wang, Gufeng and Ligler, Frances S. and Gu, Zhen}, year={2015}, pages={12096–12103} } @article{chen_nan_lu_wang_chu_gu_2015, title={Hybrid Fe3O4-Poly(acrylic acid) Nanogels for Theranostic Cancer Treatment}, volume={11}, ISSN={["1550-7041"]}, DOI={10.1166/jbn.2015.2001}, abstractNote={Multifunctional nanomedicine integrated with both therapy and diagnostics holds vast potential in cancer treatment. We developed hybrid Fe3O4-poly(acrylic acid) (PAA) nanogels for both drug delivery and magnetic resonance imaging (MRI). Superparamagnetic Fe3O4 nanoparticles were encapsulated inside porous PAA nanogels via an in situ co-precipitation approach. With successive growth of magnetic nanoparticles, the highest magnetization saturation (M(s)) value of the Fe3O4 nanoparticles in the PAA nanogels was determined as 20 emu/g. The resulting hybrid Fe3O4-PAA nanogels showed high drug loading capacity (98%) and sustained drug release in vitro. Cytotoxicity assays and cellular imaging demonstrated that the hybrid nanogels were highly biocompatible and efficiently internalized in human neuroblastoma SH-SY5Y cells. In MRI studies, the hybrid nanogels exhibited an excellent contrast in T2 weighted imaging and a high MRI sensitivity in the tumor site.}, number={5}, journal={JOURNAL OF BIOMEDICAL NANOTECHNOLOGY}, author={Chen, Ying and Nan, Jingya and Lu, Yue and Wang, Chunpeng and Chu, Fuxiang and Gu, Zhen}, year={2015}, month={May}, pages={771–779} } @article{lu_hu_lin_pacardo_wang_sun_ligler_dickey_gu_2015, title={Transformable liquid-metal nanomedicine}, volume={6}, ISSN={["2041-1723"]}, DOI={10.1038/ncomms10066}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, publisher={Springer Nature}, author={Lu, Yue and Hu, Quanyin and Lin, Yiliang and Pacardo, Dennis B. and Wang, Chao and Sun, Wujin and Ligler, Frances S. and Dickey, Michael D. and Gu, Zhen}, year={2015}, month={Dec} } @article{sun_lu_gu_2014, title={Advances in Anticancer Protein Delivery using Micro-/Nanoparticles}, volume={31}, ISSN={["1521-4117"]}, DOI={10.1002/ppsc.201400140}, abstractNote={Proteins exhibiting anticancer activities, especially those capable of discriminately killing cancer cells, have attracted increasing interest in developing protein‐based anticancer therapeutics. This Progress Report surveys recent advances in delivering anticancer proteins directly to tumor tissue for inducing apoptosis/necrosis or indirectly to antigen presenting cells for provoking immune responses. Protein delivery carriers such as inorganic particles, lipid particles, polymeric particles, DNA/protein‐based biomacromolecular particles, as well as cell based carriers are reviewed with comments on their advantages and limitations. Future challenges and opportunities are also discussed.}, number={12}, journal={PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION}, author={Sun, Wujin and Lu, Yue and Gu, Zhen}, year={2014}, month={Dec}, pages={1204–1222} } @article{sun_jiang_lu_reiff_mo_gu_2014, title={Cocoon-Like Self-Degradable DNA Nanoclew for Anticancer Drug Delivery}, volume={136}, ISSN={["0002-7863"]}, DOI={10.1021/ja5088024}, abstractNote={A bioinspired cocoon-like anticancer drug delivery system consisting of a deoxyribonuclease (DNase)-degradable DNA nanoclew (NCl) embedded with an acid-responsive DNase I nanocapsule (NCa) was developed for targeted cancer treatment. The NCl was assembled from a long-chain single-stranded DNA synthesized by rolling-circle amplification (RCA). Multiple GC-pair sequences were integrated into the NCl for enhanced loading capacity of the anticancer drug doxorubicin (DOX). Meanwhile, negatively charged DNase I was encapsulated in a positively charged acid-degradable polymeric nanogel to facilitate decoration of DNase I into the NCl by electrostatic interactions. In an acidic environment, the activity of DNase I was activated through the acid-triggered shedding of the polymeric shell of the NCa, resulting in the cocoon-like self-degradation of the NCl and promoting the release of DOX for enhanced therapeutic efficacy.}, number={42}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Sun, Wujin and Jiang, Tianyue and Lu, Yue and Reiff, Margaret and Mo, Ran and Gu, Zhen}, year={2014}, month={Oct}, pages={14722–14725} } @article{tai_mo_lu_jiang_gu_2014, title={Folding graft copolymer with pendant drug segments for co-delivery of anticancer drugs}, volume={35}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2014.05.004}, abstractNote={A graft copolymer with pendant drug segments can fold into nanostructures in a protein folding-like manner. The graft copolymer is constructed by directly polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu(CPT)-NCA) on multiple sites of poly(ethylene glycol) (PEG)-based main chain via the ring open polymerization (ROP). The "purely" conjugated anticancer agent camptothecin (CPT) is hydrophobic and serves as the principal driving force during the folding process. When exposed to water, the obtained copolymer, together with doxorubicin (Dox), another anticancer agent, can fold into monodispersed nanocarriers (with a diameter of around 50 nm) for dual-drug delivery. Equipped with a PEG shell, the nanocarriers displayed good stability and can be internalized by a variety of cancer cell lines via the lipid raft and clathrin-mediated endocytotic pathway without premature leakage, which showed a high synergetic activity of CPT and Dox toward various cancer cells. In vivo study validated that the nanocarriers exhibited strong accumulation in tumor sites and showed a prominent anticancer activity against the lung cancer xenograft mice model compared with free drugs.}, number={25}, journal={BIOMATERIALS}, author={Tai, Wanyi and Mo, Ran and Lu, Yue and Jiang, Tianyue and Gu, Zhen}, year={2014}, month={Aug}, pages={7194–7203} } @article{lu_mo_tai_sun_pacardo_qian_shen_ligler_gu_2014, title={Self-folded redox/acid dual-responsive nanocarriers for anticancer drug delivery}, volume={50}, ISSN={["1364-548X"]}, DOI={10.1039/c4cc07004f}, abstractNote={Self-folded redox/acid dual-responsive nanocarriers (RAD-NCs) are developed for physiologically triggered delivery of anticancer drugs. The evidenced redox/acid responsiveness, facile decoration of ligands, and active tumor-targeting capability of RAD-NCs suggest their potential as a promising formulation for tumor-targeted chemotherapy.}, number={95}, journal={CHEMICAL COMMUNICATIONS}, author={Lu, Yue and Mo, Ran and Tai, Wanyi and Sun, Wujin and Pacardo, Dennis B. and Qian, Chenggen and Shen, Qundong and Ligler, Frances S. and Gu, Zhen}, year={2014}, pages={15105–15108} }