Search

Your search keyword '"Kuai, Rui"' showing total 40 results
Start Over Author "Kuai, Rui" Language english
40 results on '"Kuai, Rui"'

6. A cell-based drug delivery platform for treating central nervous system inflammation

Author

Levy, Oren, Rothhammer, Veit, Mascanfroni, Ivan, Tong, Zhixiang, Kuai, Rui, De Biasio, Michael, Wang, Qingping, Majid, Tahir, Perrault, Christelle, Yeste, Ada, Kenison, Jessica E., Safaee, Helia, Musabeyezu, Juliet, Heinelt, Martina, Milton, Yuka, Kuang, Heidi, Lan, Haoyue, Siders, William, Multon, Marie-Christine, Rothblatt, Jonathan, Massadeh, Salam, Alaamery, Manal, Alhasan, Ali H., Quintana, Francisco J., and Karp, Jeffrey M.

Published
2021
Full Text
View/download PDF

19. Chemo-photothermal therapy combination elicits anti-tumor immunity against advanced metastatic cancer.

Author

Nam, Jutaek, Son, Sejin, Ochyl, Lukasz J., Kuai, Rui, Schwendeman, Anna, and Moon, James J.

Subjects
METASTASIS, IRINOTECAN, DOXORUBICIN, TREATMENT effectiveness, LIGHT sources, SQUAMOUS cell carcinoma, GOLD nanoparticles
Abstract

Photothermal therapy (PTT) is a promising cancer treatment modality, but PTT generally requires direct access to the source of light irradiation, thus precluding its utility against disseminated, metastatic tumors. Here, we demonstrate that PTT combined with chemotherapy can trigger potent anti-tumor immunity against disseminated tumors. Specifically, we have developed polydopamine-coated spiky gold nanoparticles as a new photothermal agent with extensive photothermal stability and efficiency. Strikingly, a single round of PTT combined with a sub-therapeutic dose of doxorubicin can elicit robust anti-tumor immune responses and eliminate local as well as untreated, distant tumors in >85% of animals bearing CT26 colon carcinoma. We also demonstrate their therapeutic efficacy against TC-1 submucosa-lung metastasis, a highly aggressive model for advanced head and neck squamous cell carcinoma (HNSCC). Our study sheds new light on a previously unrecognized, immunological facet of chemo-photothermal therapy and may lead to new therapeutic strategies against advanced cancer. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

21. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two: National Harbor, MD, USA. 9-13 November 2016

Author

Ager, Casey, Reilley, Matthew, Nicholas, Courtney, Bartkowiak, Todd, Jaiswal, Ashvin, Curran, Michael, Albershardt, Tina C., Bajaj, Anshika, Archer, Jacob F., Reeves, Rebecca S., Ngo, Lisa Y., Berglund, Peter, ter Meulen, Jan, Denis, Caroline, Ghadially, Hormas, Arnoux, Thomas, Chanuc, Fabien, Fuseri, Nicolas, Wilkinson, Robert W., Wagtmann, Nicolai, Morel, Yannis, Andre, Pascale, Atkins, Michael B., Carlino, Matteo S., Ribas, Antoni, Thompson, John A., Choueiri, Toni K., Hodi, F. Stephen, Hwu, Wen-Jen, McDermott, David F., Atkinson, Victoria, Cebon, Jonathan S., Fitzharris, Bernie, Jameson, Michael B., McNeil, Catriona, Hill, Andrew G., Mangin, Eric, Ahamadi, Malidi, van Vugt, Marianne, van Zutphen, Mariëlle, Ibrahim, Nageatte, Long, Georgina V., Gartrell, Robyn, Blake, Zoe, Simoes, Ines, Fu, Yichun, Saito, Takuro, Qian, Yingzhi, Lu, Yan, Saenger, Yvonne M., Budhu, Sadna, De Henau, Olivier, Zappasodi, Roberta, Schlunegger, Kyle, Freimark, Bruce, Hutchins, Jeff, Barker, Christopher A., Wolchok, Jedd D., Merghoub, Taha, Burova, Elena, Allbritton, Omaira, Hong, Peter, Dai, Jie, Pei, Jerry, Liu, Matt, Kantrowitz, Joel, Lai, Venus, Poueymirou, William, MacDonald, Douglas, Ioffe, Ella, Mohrs, Markus, Olson, William, Thurston, Gavin, Capasso, Cristian, Frascaro, Federica, Carpi, Sara, Tähtinen, Siri, Feola, Sara, Fusciello, Manlio, Peltonen, Karita, Martins, Beatriz, Sjöberg, Madeleine, Pesonen, Sari, Ranki, Tuuli, Kyruk, Lukasz, Ylösmäki, Erkko, Cerullo, Vincenzo, Cerignoli, Fabio, Xi, Biao, Guenther, Garret, Yu, Naichen, Muir, Lincoln, Zhao, Leyna, Abassi, Yama, Cervera-Carrascón, Víctor, Siurala, Mikko, Santos, João, Havunen, Riikka, Parviainen, Suvi, Hemminki, Akseli, Dalgleish, Angus, Mudan, Satvinder, DeBenedette, Mark, Plachco, Ana, Gamble, Alicia, Grogan, Elizabeth W., Krisko, John, Tcherepanova, Irina, Nicolette, Charles, Dhupkar, Pooja, Yu, Ling, Kleinerman, Eugenie S., Gordon, Nancy, Grenga, Italia, Lepone, Lauren, Gameiro, Sofia, Knudson, Karin M., Fantini, Massimo, Tsang, Kwong, Hodge, James, Donahue, Renee, Schlom, Jeffrey, Evans, Elizabeth, Bussler, Holm, Mallow, Crystal, Reilly, Christine, Torno, Sebold, Scrivens, Maria, Foster, Cathie, Howell, Alan, Balch, Leslie, Knapp, Alyssa, Leonard, John E., Paris, Mark, Fisher, Terry, Hu-Lieskovan, Siwen, Smith, Ernest, Zauderer, Maurice, Fogler, William, Franklin, Marilyn, Thayer, Matt, Saims, Dan, Magnani, John L., Gong, Jian, Gray, Michael, Fromm, George, de Silva, Suresh, Giffin, Louise, Xu, Xin, Rose, Jason, Schreiber, Taylor H., Gameiro, Sofia R., Clavijo, Paul E., Allen, Clint T., Hodge, James W., Tsang, Kwong Y., Grogan, Jane, Manieri, Nicholas, Chiang, Eugene, Caplazi, Patrick, Yadav, Mahesh, Hagner, Patrick, Chiu, Hsiling, Waldman, Michelle, Klippel, Anke, Thakurta, Anjan, Pourdehnad, Michael, Gandhi, Anita, Henrich, Ian, Quick, Laura, Young, Rob, Chou, Margaret, Hotson, Andrew, Willingham, Stephen, Ho, Po, Choy, Carmen, Laport, Ginna, McCaffery, Ian, Miller, Richard, Tipton, Kimberly A., Wong, Kenneth R., Singson, Victoria, Wong, Chihunt, Chan, Chanty, Huang, Yuanhiu, Liu, Shouchun, Richardson, Jennifer H., Kavanaugh, W. Michael, West, James, Irving, Bryan A., Jaini, Ritika, Loya, Matthew, Eng, Charis, Johnson, Melissa L., Adjei, Alex A., Opyrchal, Mateusz, Ramalingam, Suresh, Janne, Pasi A., Dominguez, George, Gabrilovich, Dmitry, de Leon, Laura, Hasapidis, Jeannette, Diede, Scott J., Ordentlich, Peter, Cruickshank, Scott, Meyers, Michael L., Hellmann, Matthew D., Kalinski, Pawel, Zureikat, Amer, Edwards, Robert, Muthuswamy, Ravi, Obermajer, Nataša, Urban, Julie, Butterfield, Lisa H., Gooding, William, Zeh, Herbert, Bartlett, David, Zubkova, Olga, Agapova, Larissa, Kapralova, Marina, Krasovskaia, Liudmila, Ovsepyan, Armen, Lykov, Maxim, Eremeev, Artem, Bokovanov, Vladimir, Grigoryeva, Olga, Karpov, Andrey, Ruchko, Sergey, Shuster, Alexandr, Khalil, Danny N., Campesato, Luis Felipe, Li, Yanyun, Lazorchak, Adam S., Patterson, Troy D., Ding, Yueyun, Sasikumar, Pottayil, Sudarshan, Naremaddepalli, Gowda, Nagaraj, Ramachandra, Raghuveer, Samiulla, Dodheri, Giri, Sanjeev, Eswarappa, Rajesh, Ramachandra, Murali, Tuck, David, Wyant, Timothy, Leshem, Jasmin, Liu, Xiu-fen, Bera, Tapan, Terabe, Masaki, Bossenmaier, Birgit, Niederfellner, Gerhard, Reiter, Yoram, Pastan, Ira, Xia, Leiming, Xia, Yang, Hu, Yangyang, Wang, Yi, Bao, Yangyi, Dai, Fu, Huang, Shiang, Hurt, Elaine, Hollingsworth, Robert E., Lum, Lawrence G., Chang, Alfred E., Wicha, Max S., Li, Qiao, Mace, Thomas, Makhijani, Neil, Talbert, Erin, Young, Gregory, Guttridge, Denis, Conwell, Darwin, Lesinski, Gregory B., Gonzales, Rodney JM Macedo, Huffman, Austin P., Wang, Ximi K., Reshef, Ran, MacKinnon, Andy, Chen, Jason, Gross, Matt, Marguier, Gisele, Shwonek, Peter, Sotirovska, Natalija, Steggerda, Susanne, Parlati, Francesco, Makkouk, Amani, Bennett, Mark K., Emberley, Ethan, Huang, Tony, Li, Weiqun, Neou, Silinda, Pan, Alison, Zhang, Jing, Zhang, Winter, Marshall, Netonia, Marron, Thomas U., Agudo, Judith, Brown, Brian, Brody, Joshua, McQuinn, Christopher, Farren, Matthew, Komar, Hannah, Shakya, Reena, Ludwug, Thomas, Morillon, Y. Maurice, Hammond, Scott A., Greiner, John W., Nath, Pulak R., Schwartz, Anthony L., Maric, Dragan, Roberts, David D., Naing, Aung, Papadopoulos, Kyriakos P., Autio, Karen A., Wong, Deborah J., Patel, Manish, Falchook, Gerald, Pant, Shubham, Ott, Patrick A., Whiteside, Melinda, Patnaik, Amita, Mumm, John, Janku, Filip, Chan, Ivan, Bauer, Todd, Colen, Rivka, VanVlasselaer, Peter, Brown, Gail L., Tannir, Nizar M., Oft, Martin, Infante, Jeffrey, Lipson, Evan, Gopal, Ajay, Neelapu, Sattva S., Armand, Philippe, Spurgeon, Stephen, Leonard, John P., Sanborn, Rachel E., Melero, Ignacio, Gajewski, Thomas F., Maurer, Matthew, Perna, Serena, Gutierrez, Andres A., Clynes, Raphael, Mitra, Priyam, Suryawanshi, Satyendra, Gladstone, Douglas, Callahan, Margaret K., Crooks, James, Brown, Sheila, Gauthier, Audrey, de Boisferon, Marc Hillairet, MacDonald, Andrew, Brunet, Laura Rosa, Rothwell, William T., Bell, Peter, Wilson, James M., Sato-Kaneko, Fumi, Yao, Shiyin, Zhang, Shannon S., Carson, Dennis A., Guiducci, Cristina, Coffman, Robert L., Kitaura, Kazutaka, Matsutani, Takaji, Suzuki, Ryuji, Hayashi, Tomoko, Cohen, Ezra E. W., Schaer, David, Li, Yanxia, Dobkin, Julie, Amatulli, Michael, Hall, Gerald, Doman, Thompson, Manro, Jason, Dorsey, Frank Charles, Sams, Lillian, Holmgaard, Rikke, Persaud, Krishnadatt, Ludwig, Dale, Surguladze, David, Kauh, John S., Novosiadly, Ruslan, Kalos, Michael, Driscoll, Kyla, Pandha, Hardev, Ralph, Christy, Harrington, Kevin, Curti, Brendan, Akerley, Wallace, Gupta, Sumati, Melcher, Alan, Mansfield, David, Kaufman, David R., Schmidt, Emmett, Grose, Mark, Davies, Bronwyn, Karpathy, Roberta, Shafren, Darren, Shamalov, Katerina, Cohen, Cyrille, Sharma, Naveen, Allison, James, Shekarian, Tala, Valsesia-Wittmann, Sandrine, Caux, Christophe, Marabelle, Aurelien, Slomovitz, Brian M., Moore, Kathleen M., Youssoufian, Hagop, Posner, Marshall, Tewary, Poonam, Brooks, Alan D., Xu, Ya-Ming, Wijeratne, Kithsiri, Gunatilaka, Leslie A. A., Sayers, Thomas J., Vasilakos, John P., Alston, Tesha, Dovedi, Simon, Elvecrog, James, Grigsby, Iwen, Herbst, Ronald, Johnson, Karen, Moeckly, Craig, Mullins, Stefanie, Siebenaler, Kristen, SternJohn, Julius, Tilahun, Ashenafi, Tomai, Mark A., Vogel, Katharina, Vietsch, Eveline E., Wellstein, Anton, Wythes, Martin, Crosignani, Stefano, Tumang, Joseph, Alekar, Shilpa, Bingham, Patrick, Cauwenberghs, Sandra, Chaplin, Jenny, Dalvie, Deepak, Denies, Sofie, De Maeseneire, Coraline, Feng, JunLi, Frederix, Kim, Greasley, Samantha, Guo, Jie, Hardwick, James, Kaiser, Stephen, Jessen, Katti, Kindt, Erick, Letellier, Marie-Claire, Li, Wenlin, Maegley, Karen, Marillier, Reece, Miller, Nichol, Murray, Brion, Pirson, Romain, Preillon, Julie, Rabolli, Virginie, Ray, Chad, Ryan, Kevin, Scales, Stephanie, Srirangam, Jay, Solowiej, Jim, Stewart, Al, Streiner, Nicole, Torti, Vince, Tsaparikos, Konstantinos, Zheng, Xianxian, Driessens, Gregory, Gomes, Bruno, Kraus, Manfred, Xu, Chunxiao, Zhang, Yanping, Kradjian, Giorgio, Qin, Guozhong, Qi, Jin, Xu, Xiaomei, Marelli, Bo, Yu, Huakui, Guzman, Wilson, Tighe, Rober, Salazar, Rachel, Lo, Kin-Ming, English, Jessie, Radvanyi, Laszlo, Lan, Yan, Postow, Michael, Senbabaoglu, Yasin, Gasmi, Billel, Zhong, Hong, Liu, Cailian, Hirschhorhn-Cymerman, Daniel, Zha, Yuanyuan, Malnassy, Gregory, Fulton, Noreen, Park, Jae-Hyun, Stock, Wendy, Nakamura, Yusuke, Liu, Hongtao, Ju, Xiaoming, Kosoff, Rachelle, Ramos, Kimberly, Coder, Brandon, Petit, Robert, Princiotta, Michael, Perry, Kyle, Zou, Jun, Arina, Ainhoa, Fernandez, Christian, Zheng, Wenxin, Beckett, Michael A., Mauceri, Helena J., Fu, Yang-Xin, Weichselbaum, Ralph R., Lewis, Whitney, Han, Yanyan, Wu, Yeting, Yang, Chou, Huang, Jing, Wu, Dongyun, Li, Jin, Liang, Xiaoling, Zhou, Xiangjun, Hou, Jinlin, Hassan, Raffit, Jahan, Thierry, Antonia, Scott J., Kindler, Hedy L., Alley, Evan W., Honarmand, Somayeh, Liu, Weiqun, Leong, Meredith L., Whiting, Chan C., Nair, Nitya, Enstrom, Amanda, Lemmens, Edward E., Tsujikawa, Takahiro, Kumar, Sushil, Coussens, Lisa M., Murphy, Aimee L., Brockstedt, Dirk G., Koch, Sven D., Sebastian, Martin, Weiss, Christian, Früh, Martin, Pless, Miklos, Cathomas, Richard, Hilbe, Wolfgang, Pall, Georg, Wehler, Thomas, Alt, Jürgen, Bischoff, Helge, Geissler, Michael, Griesinger, Frank, Kollmeier, Jens, Papachristofilou, Alexandros, Doener, Fatma, Fotin-Mleczek, Mariola, Hipp, Madeleine, Hong, Henoch S., Kallen, Karl-Josef, Klinkhardt, Ute, Stosnach, Claudia, Scheel, Birgit, Schroeder, Andreas, Seibel, Tobias, Gnad-Vogt, Ulrike, Zippelius, Alfred, Park, Ha-Ram, Ahn, Yong-Oon, Kim, Tae Min, Kim, Soyeon, Kim, Seulki, Lee, Yu Soo, Keam, Bhumsuk, Kim, Dong-Wan, Heo, Dae Seog, Pilon-Thomas, Shari, Weber, Amy, Morse, Jennifer, Kodumudi, Krithika, Liu, Hao, Mullinax, John, Sarnaik, Amod A., Pike, Luke, Bang, Andrew, Balboni, Tracy, Taylor, Allison, Spektor, Alexander, Wilhite, Tyler, Krishnan, Monica, Cagney, Daniel, Alexander, Brian, Aizer, Ayal, Buchbinder, Elizabeth, Awad, Mark, Ghandi, Leena, Schoenfeld, Jonathan, Lessey-Morillon, Elizabeth, Ridnour, Lisa, Segal, Neil H., Sharma, Manish, Le, Dung T., Ferris, Robert L., Zelenetz, Andrew D., Levy, Ronald, Lossos, Izidore S., Jacobson, Caron, Ramchandren, Radhakrishnan, Godwin, John, Colevas, A. Dimitrios, Meier, Roland, Krishnan, Suba, Gu, Xuemin, Neely, Jaclyn, Timmerman, John, Vanpouille-Box, Claire I., Formenti, Silvia C., Demaria, Sandra, Wennerberg, Erik, Mediero, Aranzazu, Cronstein, Bruce N., Gustafson, Michael P., DiCostanzo, AriCeli, Wheatley, Courtney, Kim, Chul-Ho, Bornschlegl, Svetlana, Gastineau, Dennis A., Johnson, Bruce D., Dietz, Allan B., MacDonald, Cameron, Bucsek, Mark, Qiao, Guanxi, Hylander, Bonnie, Repasky, Elizabeth, Turbitt, William J., Xu, Yitong, Mastro, Andrea, Rogers, Connie J., Withers, Sita, Wang, Ziming, Khuat, Lam T., Dunai, Cordelia, Blazar, Bruce R., Longo, Dan, Rebhun, Robert, Grossenbacher, Steven K., Monjazeb, Arta, Murphy, William J., Rowlinson, Scott, Agnello, Giulia, Alters, Susan, Lowe, David, Scharping, Nicole, Menk, Ashley V., Whetstone, Ryan, Zeng, Xue, Delgoffe, Greg M., Santos, Patricia M., Shi, Jian, Delgoffe, Greg, Nagasaka, Misako, Sukari, Ammar, Byrne-Steele, Miranda, Pan, Wenjing, Hou, Xiaohong, Brown, Brittany, Eisenhower, Mary, Han, Jian, Collins, Natalie, Manguso, Robert, Pope, Hans, Shrestha, Yashaswi, Boehm, Jesse, Haining, W. Nicholas, Cron, Kyle R., Sivan, Ayelet, Aquino-Michaels, Keston, Orecchioni, Marco, Bedognetti, Davide, Hendrickx, Wouter, Fuoco, Claudia, Spada, Filomena, Sgarrella, Francesco, Cesareni, Gianni, Marincola, Francesco, Kostarelos, Kostas, Bianco, Alberto, Delogu, Lucia, Roelands, Jessica, Boughorbel, Sabri, Decock, Julie, Presnell, Scott, Wang, Ena, Marincola, Franco M., Kuppen, Peter, Ceccarelli, Michele, Rinchai, Darawan, Chaussabel, Damien, Miller, Lance, Nguyen, Andrew, Sanborn, J. Zachary, Vaske, Charles, Rabizadeh, Shahrooz, Niazi, Kayvan, Benz, Steven, Patel, Shashank, Restifo, Nicholas, White, James, Angiuoli, Sam, Sausen, Mark, Jones, Sian, Sevdali, Maria, Simmons, John, Velculescu, Victor, Diaz, Luis, Zhang, Theresa, Sims, Jennifer S., Barton, Sunjay M., Kadenhe-Chiweshe, Angela, Dela Cruz, Filemon, Turk, Andrew T., Mazzeo, Christopher F., Kung, Andrew L., Bruce, Jeffrey N., Yamashiro, Darrell J., Connolly, Eileen P., Baird, Jason, Crittenden, Marka, Friedman, David, Xiao, Hong, Leidner, Rom, Bell, Bryan, Young, Kristina, Gough, Michael, Bian, Zhen, Kidder, Koby, Liu, Yuan, Curran, Emily, Chen, Xiufen, Corrales, Leticia P., Kline, Justin, Aguilar, Ethan G., Guerriero, Jennifer, Sotayo, Alaba, Ponichtera, Holly, Pourzia, Alexandra, Schad, Sara, Carrasco, Ruben, Lazo, Suzan, Bronson, Roderick, Letai, Anthony, Kornbluth, Richard S., Gupta, Sachin, Termini, James, Guirado, Elizabeth, Stone, Geoffrey W., Meyer, Christina, Helming, Laura, Wilson, Nicholas, Hofmeister, Robert, Neubert, Natalie J., Tillé, Laure, Barras, David, Soneson, Charlotte, Baumgaertner, Petra, Rimoldi, Donata, Gfeller, David, Delorenzi, Mauro, Fuertes Marraco, Silvia A., Speiser, Daniel E., Abraham, Tara S., Xiang, Bo, Magee, Michael S., Waldman, Scott A., Snook, Adam E., Blogowski, Wojciech, Zuba-Surma, Ewa, Budkowska, Marta, Salata, Daria, Dolegowska, Barbara, Starzynska, Teresa, Chan, Leo, Somanchi, Srinivas, McCulley, Kelsey, Lee, Dean, Buettner, Nico, Shi, Feng, Myers, Paisley T., Curbishley, Stuart, Penny, Sarah A., Steadman, Lora, Millar, David, Speers, Ellen, Ruth, Nicola, Wong, Gabriel, Thimme, Robert, Adams, David, Cobbold, Mark, Thomas, Remy, Al-Muftah, Mariam, Wong, Michael KK, Morse, Michael, Clark, Joseph I., Kaufman, Howard L., Daniels, Gregory A., Hua, Hong, Rao, Tharak, Dutcher, Janice P., Kang, Kai, Saunthararajah, Yogen, Velcheti, Vamsidhar, Kumar, Vikas, Anwar, Firoz, Verma, Amita, Chheda, Zinal, Kohanbash, Gary, Sidney, John, Okada, Kaori, Shrivastav, Shruti, Carrera, Diego A., Liu, Shuming, Jahan, Naznin, Mueller, Sabine, Pollack, Ian F., Carcaboso, Angel M., Sette, Alessandro, Hou, Yafei, Okada, Hideho, Field, Jessica J., Zeng, Weiping, Shih, Vincent FS, Law, Che-Leung, Senter, Peter D., Gardai, Shyra J., Okeley, Nicole M., Abelin, Jennifer G., Saeed, Abu Z., Malaker, Stacy A., Shabanowitz, Jeffrey, Ward, Stephen T., Hunt, Donald F., Profusek, Pam, Wood, Laura, Shepard, Dale, Grivas, Petros, Kapp, Kerstin, Volz, Barbara, Oswald, Detlef, Wittig, Burghardt, Schmidt, Manuel, Sefrin, Julian P., Hillringhaus, Lars, Lifke, Valeria, Lifke, Alexander, Skaletskaya, Anna, Ponte, Jose, Chittenden, Thomas, Setiady, Yulius, Sivado, Eva, Thomas, Vincent, El Alaoui, Meddy, Papot, Sébastien, Dumontet, Charles, Dyson, Mike, McCafferty, John, El Alaoui, Said, Bommareddy, Praveen K., Zloza, Andrew, Kohlhapp, Frederick, Silk, Ann W., Jhawar, Sachin, Paneque, Tomas, Newman, Jenna, Beltran, Pedro, Cao, Felicia, Hong, Bang-Xing, Rodriguez-Cruz, Tania, Song, Xiao-Tong, Gottschalk, Stephen, Calderon, Hugo, Illingworth, Sam, Brown, Alice, Fisher, Kerry, Seymour, Len, Champion, Brian, Eriksson, Emma, Wenthe, Jessica, Hellström, Ann-Charlotte, Paul-Wetterberg, Gabriella, Loskog, Angelica, Milenova, Ioanna, Ståhle, Magnus, Jarblad-Leja, Justyna, Ullenhag, Gustav, Dimberg, Anna, Moreno, Rafael, Alemany, Ramon, Goyal, Sharad, Silk, Ann, Mehnert, Janice, Gabrail, Nashat, Bryan, Jennifer, Medina, Daniel, Mitchell, Leah, Yagiz, Kader, Lopez, Fernando, Mendoza, Daniel, Munday, Anthony, Gruber, Harry, Jolly, Douglas, Fuhrmann, Steven, Radoja, Sasa, Tan, Wei, Pourchet, Aldo, Frey, Alan, Mohr, Ian, Mulvey, Matthew, Andtbacka, Robert H. I., Ross, Merrick, Agarwala, Sanjiv, Grossmann, Kenneth, Taylor, Matthew, Vetto, John, Neves, Rogerio, Daud, Adil, Khong, Hung, Meek, Stephanie M., Ungerleider, Richard, Welden, Scott, Tanaka, Maki, Williams, Matthew, Hallmeyer, Sigrun, Fox, Bernard, Feng, Zipei, Paustian, Christopher, Bifulco, Carlo, Zafar, Sadia, Hemminki, Otto, Bramante, Simona, Vassilev, Lotta, Wang, Hongjie, Lieber, Andre, Hemmi, Silvio, de Gruijl, Tanja, Kanerva, Anna, Ansari, Tameem, Sundararaman, Srividya, Roen, Diana, Lehmann, Paul, Bloom, Anja C., Bender, Lewis H., Walters, Ian B., Berzofsky, Jay A., Chapelin, Fanny, Ahrens, Eric T., DeFalco, Jeff, Harbell, Michael, Manning-Bog, Amy, Scholz, Alexander, Zhang, Danhui, Baia, Gilson, Tan, Yann Chong, Sokolove, Jeremy, Kim, Dongkyoon, Williamson, Kevin, Chen, Xiaomu, Colrain, Jillian, Santo, Gregg Espiritu, Nguyen, Ngan, Volkmuth, Wayne, Greenberg, Norman, Robinson, William, Emerling, Daniel, Drake, Charles G., Petrylak, Daniel P., Antonarakis, Emmanuel S., Kibel, Adam S., Chang, Nancy N., Vu, Tuyen, Campogan, Dwayne, Haynes, Heather, Trager, James B., Sheikh, Nadeem A., Quinn, David I., Kirk, Peter, Addepalli, Murali, Chang, Thomas, Zhang, Ping, Konakova, Marina, Hagihara, Katsunobu, Pai, Steven, VanderVeen, Laurie, Obalapur, Palakshi, Kuo, Peiwen, Quach, Phi, Fong, Lawrence, Charych, Deborah H., Zalevsky, Jonathan, Langowski, John L., Kirksey, Yolanda, Nutakki, Ravi, Kolarkar, Shalini, Pena, Rhoneil, Hoch, Ute, Doberstein, Stephen K., Cha, John, Mallon, Zach, Perez, Myra, McDaniel, Amanda, Anand, Snjezana, Uecker, Darrin, Nuccitelli, Richard, Wieckowski, Eva, Muthuswamy, Ravikumar, Ravindranathan, Roshni, Renrick, Ariana N., Thounaojam, Menaka, Thomas, Portia, Pellom, Samuel, Shanker, Anil, Dudimah, Duafalia, Brooks, Alan, Su, Yu-Lin, Adamus, Tomasz, Zhang, Qifang, Nechaev, Sergey, Kortylewski, Marcin, Wei, Spencer, Anderson, Clark, Tang, Chad, Schoenhals, Jonathan, Tsouko, Efrosini, Heymach, John, de Groot, Patricia, Chang, Joe, Hess, Kenneth R., Diab, Adi, Sharma, Padmanee, Hong, David, Welsh, James, Parsons, Andrea J., Leleux, Jardin, Ascarateil, Stephane, Koziol, Marie Eve, Bai, Dina, Dai, Peihong, Wang, Weiyi, Yang, Ning, Shuman, Stewart, Deng, Liang, Dillon, Patrick, Petroni, Gina, Brenin, David, Bullock, Kim, Olson, Walter, Smolkin, Mark E., Smith, Kelly, Nail, Carmel, Slingluff, Craig L., Sharma, Meenu, Fa’ak, Faisal, Janssen, Louise, Khong, Hiep, Xiao, Zhilan, Hailemichael, Yared, Singh, Manisha, Vianden, Christina, Overwijk, Willem W., Facciabene, Andrea, Stefano, Pierini, Chongyung, Fang, Rafail, Stavros, Nielsen, Michael, Vanderslice, Peter, Woodside, Darren G., Market, Robert V., Biediger, Ronald J., Marathi, Upendra K., Hollevoet, Kevin, Geukens, Nick, Declerck, Paul, Joly, Nathalie, McIntosh, Laura, Paramithiotis, Eustache, Rizell, Magnus, Sternby, Malin, Andersson, Bengt, Karlsson-Parra, Alex, Kuai, Rui, Ochyl, Lukasz, Schwendeman, Anna, Moon, James, Deng, Weiwen, Hudson, Thomas E., Hanson, Bill, Rae, Chris S., Burrill, Joel, Skoble, Justin, Katibah, George, deVries, Michele, Lauer, Peter, Dubensky, Thomas W., Chen, Xin, Zhou, Li, Ren, Xiubao, Aggarwal, Charu, Mangrolia, Drishty, Cohen, Roger, Weinstein, Gregory, Morrow, Matthew, Bauml, Joshua, Kraynyak, Kim, Boyer, Jean, Yan, Jian, Lee, Jessica, Humeau, Laurent, Oyola, Sandra, Duff, Susan, Weiner, David, Yang, Zane, Bagarazzi, Mark, McNeel, Douglas G., Eickhoff, Jens, Jeraj, Robert, Staab, Mary Jane, Straus, Jane, Rekoske, Brian, Liu, Glenn, Melssen, Marit, Grosh, William, Varhegyi, Nikole, Galeassi, Nadejda, Deacon, Donna H., Gaughan, Elizabeth, Ghisoli, Maurizio, Barve, Minal, Mennel, Robert, Wallraven, Gladice, Manning, Luisa, Senzer, Neil, Nemunaitis, John, Ogasawara, Masahiro, Ota, Shuichi, Peace, Kaitlin M., Hale, Diane F., Vreeland, Timothy J., Jackson, Doreen O., Berry, John S., Trappey, Alfred F., Herbert, Garth S., Clifton, Guy T., Hardin, Mark O., Toms, Anne, Qiao, Na, Litton, Jennifer, Peoples, George E., Mittendorf, Elizabeth A., Ghamsari, Lila, Flano, Emilio, Jacques, Judy, Liu, Biao, Havel, Jonathan, Makarov, Vladimir, Chan, Timothy A., Flechtner, Jessica B., Facciponte, John, Ugel, Stefano, De Sanctis, Francesco, Coukos, George, Paris, Sébastien, Pottier, Agnes, Levy, Laurent, Lu, Bo, Cappuccini, Federica, Pollock, Emily, Bryant, Richard, Hamdy, Freddie, Hill, Adrian, Redchenko, Irina, Sultan, Hussein, Kumai, Takumi, Fesenkova, Valentyna, Celis, Esteban, Fernando, Ingrid, Palena, Claudia, David, Justin M., Gabitzsch, Elizabeth, Jones, Frank, Gulley, James L., Herranz, Mireia Uribe, Wada, Hiroshi, Shimizu, Atsushi, Osada, Toshihiro, Fukaya, Satoshi, Sasaki, Eiji, Abolhalaj, Milad, Askmyr, David, Lundberg, Kristina, Albrekt, Ann-Sofie, Greiff, Lennart, Lindstedt, Malin, Flies, Dallas B., Higuchi, Tomoe, Ornatowski, Wojciech, Harris, Jaryse, Adams, Sarah F., Aguilera, Todd, Rafat, Marjan, Castellini, Laura, Shehade, Hussein, Kariolis, Mihalis, Jang, Dadi, vonEbyen, Rie, Graves, Edward, Ellies, Lesley, Rankin, Erinn, Koong, Albert, Giaccia, Amato, Ajina, Reham, Wang, Shangzi, Smith, Jill, Pierobon, Mariaelena, Jablonski, Sandra, Petricoin, Emanuel, Weiner, Louis M., Sherry, Lorcan, Waller, John, Anderson, Mark, Bigley, Alison, Bernatchez, Chantale, Haymaker, Cara, Kluger, Harriet, Tetzlaff, Michael, Jackson, Natalie, Gergel, Ivan, Tagliaferri, Mary, Hwu, Patrick, Snzol, Mario, Hurwitz, Michael, Barberi, Theresa, Martin, Allison, Suresh, Rahul, Barakat, David, Harris-Bookman, Sarah, Drake, Charles, Friedman, Alan, Berkey, Sara, Downs-Canner, Stephanie, Edwards, Robert P., Curiel, Tyler, Odunsi, Kunle, Bruno, Tullia C., Moore, Brandon, Squalls, Olivia, Ebner, Peggy, Waugh, Katherine, Mitchell, John, Franklin, Wilbur, Merrick, Daniel, McCarter, Martin, Palmer, Brent, Kern, Jeffrey, Vignali, Dario, Slansky, Jill, Chan, Anissa S. H., Qiu, Xiaohong, Fraser, Kathryn, Jonas, Adria, Ottoson, Nadine, Gordon, Keith, Kangas, Takashi O., Leonardo, Steven, Ertelt, Kathleen, Walsh, Richard, Uhlik, Mark, Graff, Jeremy, Bose, Nandita, Gupta, Ravi, Mandloi, Nitin, Paul, Kiran, Patil, Ashwini, Sathian, Rekha, Mohan, Aparna, Manoharan, Malini, Chaudhuri, Amitabha, Chen, Yu, Lin, Jing, Ye, Yun-bin, Xu, Chun-wei, Chen, Gang, Guo, Zeng-qing, Komarov, Andrey, Chenchik, Alex, Makhanov, Michael, Frangou, Costa, Zheng, Yi, Coltharp, Carla, Unfricht, Darryn, Dilworth, Ryan, Fridman, Leticia, Liu, Linying, Rajopadhye, Milind, Miller, Peter, Concha-Benavente, Fernando, Bauman, Julie, Trivedi, Sumita, Srivastava, Raghvendra, Ohr, James, Heron, Dwight, Duvvuri, Uma, Kim, Seungwon, Torrey, Heather, Mera, Toshi, Okubo, Yoshiaki, Vanamee, Eva, Foster, Rosemary, Faustman, Denise, Stack, Edward, Izaki, Daisuke, Beck, Kristen, Jia, Dan Tong, Armenta, Paul, White-Stern, Ashley, Marks, Douglas, Taback, Bret, Horst, Basil, Glickman, Laura Hix, Kanne, David B., Gauthier, Kelsey S., Desbien, Anthony L., Francica, Brian, Leong, Justin L., Sung, Leonard, Metchette, Ken, Kasibhatla, Shailaja, Pferdekamper, Anne Marie, Zheng, Lianxing, Cho, Charles, Feng, Yan, McKenna, Jeffery M., Tallarico, John, Bender, Steven, Ndubaku, Chudi, McWhirter, Sarah M., Gugel, Elena Gonzalez, Bell, Charles J. M., Munk, Adiel, Muniz, Luciana, Bhardwaj, Nina, Zhao, Fei, Evans, Kathy, Xiao, Christine, Holtzhausen, Alisha, Hanks, Brent A., Scholler, Nathalie, Yin, Catherine, Van der Meijs, Pien, Prantner, Andrew M., Krejsa, Cecile M., Smith, Leia, Johnson, Brian, Branstetter, Daniel, Stein, Paul L., Jaen, Juan C., Tan, Joanne BL, Chen, Ada, Park, Timothy, Powers, Jay P., Sexton, Holly, Xu, Guifen, Young, Steve W., Schindler, Ulrike, Deng, Wentao, Klinke, David John, Komar, Hannah M., Serpa, Gregory, Elnaggar, Omar, Hart, Philip, Schmidt, Carl, Dillhoff, Mary, Jin, Ming, Ostrowski, Michael C., Koti, Madhuri, Au, Katrina, Peterson, Nichole, Truesdell, Peter, Reid-Schachter, Gillian, Graham, Charles, Craig, Andrew, Francis, Julie-Ann, Kotlan, Beatrix, Balatoni, Timea, Farkas, Emil, Toth, Laszlo, Ujhelyi, Mihaly, Savolt, Akos, Doleschall, Zoltan, Horvath, Szabolcs, Eles, Klara, Olasz, Judit, Csuka, Orsolya, Kasler, Miklos, Liszkay, Gabriella, Barnea, Eytan, Blakely, Collin, Flynn, Patrick, Goodman, Reid, Bueno, Raphael, Sugarbaker, David, Jablons, David, Broaddus, V. Courtney, West, Brian, Kunk, Paul R., Obeid, Joseph M., Winters, Kevin, Pramoonjago, Patcharin, Stelow, Edward B., Bauer, Todd W., Rahma, Osama E., Lamble, Adam, Kosaka, Yoko, Huang, Fei, Saser, Kate A., Adams, Homer, Tognon, Christina E., Laderas, Ted, McWeeney, Shannon, Loriaux, Marc, Tyner, Jeffery W., Druker, Brian J., Lind, Evan F., Liu, Zhuqing, Lu, Shanhong, Kane, Lawrence P., Shayan, Gulidanna, Femel, Julia, Lane, Ryan, Booth, Jamie, Lund, Amanda W., Rodriguez, Anthony, Engelhard, Victor H., Metelli, Alessandra, Wu, Bill X., Fugle, Caroline W., Saleh, Rachidi, Sun, Shaoli, Wu, Jennifer, Liu, Bei, Li, Zihai, Morris, Zachary S., Guy, Emily I., Heinze, Clinton, Kler, Jasdeep, Gressett, Monica M., Werner, Lauryn R., Gillies, Stephen D., Korman, Alan J., Loibner, Hans, Hank, Jacquelyn A., Rakhmilevich, Alexander L., Harari, Paul M., Sondel, Paul M., Huelsmann, Erica, Broucek, Joseph, Brech, Dorothee, Straub, Tobias, Irmler, Martin, Beckers, Johannes, Buettner, Florian, Schaeffeler, Elke, Schwab, Matthias, Noessner, Elfriede, Wolfreys, Alison, Da Costa, Andre, Silva, John, Crosby, Andrea, Staelens, Ludovicus, Craggs, Graham, Cauvin, Annick, Mason, Sean, Paterson, Alison M., Lake, Andrew C., Armet, Caroline M., O’Connor, Rachel W., Hill, Jonathan A., Normant, Emmanuel, Adam, Ammar, Biniszkiewicz, Detlev M., Chappel, Scott C., Palombella, Vito J., Holland, Pamela M., Becker, Annette, Leleti, Manmohan R., Newcomb, Eric, Tan, Joanne B. L., Rapisuwon, Suthee, Radfar, Arash, Gardner, Kellie, Gibney, Geoffrey, Atkins, Michael, Rennier, Keith R., Crowder, Robert, Wang, Ping, Pachynski, Russell K., Carrero, Rosa M. Santana, Rivas, Sarai, Beceren-Braun, Figen, Anthony, Scott, Schluns, Kimberly S., Sawant, Deepali, Chikina, Maria, Yano, Hiroshi, Workman, Creg, Salerno, Elise, Mauldin, Ileana, Deacon, Donna, Shea, Sofia, Pinczewski, Joel, Gajewski, Thomas, Spranger, Stefani, Horton, Brendan, Suzuki, Akiko, Leland, Pamela, Joshi, Bharat H., Puri, Raj K., Sweis, Randy F., Bao, Riyue, Luke, Jason, Theodoraki, Marie-Nicole, Mogundo, Frances-Mary, Won, Haejung, Moreira, Dayson, Gao, Chan, Zhao, Xingli, Duttagupta, Priyanka, Jones, Jeremy, D’Apuzzo, Massimo, and Pal, Sumanta

Published
2016
Full Text
View/download PDF

22. Comparison of four different peptides to enhance accumulation of liposomes into the brain.

Author

Qin, Yao, Zhang, Qianyu, Chen, Huali, Yuan, Wenmin, Kuai, Rui, Xie, Fulan, Zhang, Li, Wang, Xiaoxiao, Zhang, Zhirong, Liu, Ji, and He, Qin

Subjects
PEPTIDES, LIPOSOMES, DRUG efficacy, DRUG delivery systems, AMINO acids, TARGETED drug delivery, ENDOTHELIUM
Abstract

The cell penetrating peptide TAT, which appears to enter cells with alacrity, can pass through the BBB efficiently. It has been indentified to enhance the brain delivery of the liposome. However, little was known about its mechanism. TAT contains a basic region consisting of six arginine and two lysine residues. These eight basic amino acids seem to be the key to its highly efficient membrane translocation and brain delivery. In this study, four selected peptides are synthesized. (1) TAT peptide with terminal Cysteine (Cys-AYGRKKRRQRRR). (2) TAT peptide with disordered sequence (Cys-RKARYRGRKRQR). (3) Glycine and glutamic acid substituted TAT peptide (Cys-AYGGQQGGQGGG). (4) R8 (Cys-RRRRRRRR). Liposomes were chosen as the delivery vehicle. The peptide was covalently bonded with the liposome. We compare four peptides for their brain targeting potential, and investigate their ability to target liposomes to the brain in vitro and in vivo. The cellular uptake of these four liposomes by brain capillary endothelial cells (BCECs) of rats and C6s and the mechanism of the pathway of endocytosis were explored. Biodistribution in vivo was also investigated qualitatively and quantitatively. The results showed that the charge of the peptide played an important role in enhancing its brain delivery. The sequence had little to do with its membrane translocation and brain delivery indicated there might be no specific receptor or transporter for the Tat peptide. [ABSTRACT FROM AUTHOR]

Published
2012
Full Text
View/download PDF

23. In vitro and in vivo investigation of glucose-mediated brain-targeting liposomes.

Author

Qin, Yao, Fan, Wei, Chen, Huali, Yao, Nian, Tang, Wenwei, Tang, Jie, Yuan, Wenmin, Kuai, Rui, Zhang, Zhirong, Wu, Yong, and He, Qin

Subjects
CHOLESTEROL, LIPOSOMES, GLUCOSE, ENDOTHELIUM, TARGETED drug delivery
Abstract

New glycosyl derivative of cholesterol was synthesized as a material for preparing novel liposome to overcome the ineffective delivery of normal drug formulations to brain by targeting the (glucose transporters) GLUTs on the BBB. Coumarin-6 was used as fluorescent probe. The results have shown that the cytotoxicity for the brain capillary endothelial cells (BCECs) of the glucose-mediated brain targeting liposome containing coumarin-6 was less than that of conventional liposome. The BBB model in vitro was established by coculturing of BCECs and astrocytes (ACs) of rat to test the transendothelial ability crossing the BBB. The transendothelial ability was confirmed strengthen alone with the amount of the new glycosyl derivative of cholesterol used in liposome. After i.v. administration of LIP, control liposome (CLP), and GLP-4, the AUC0–t of coumarin-6 for GLP-4 was 2.85 times higher than that of LIP, and 3.33 times higher than that of CLP. The Cmax of CLP-4 was 1.43 times higher than that of LIP, and 3.10 times higher than that of CLP. Both pharmacokinetics and distribution in mice were also investigated to show that this novel brain targeting drug delivery system was promising. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

24. RalA exerts an inhibitory effect on IL-1β/IL-18 secretion by blocking NLRP3 inflammasome activation in levornidazole-treated human THP-1 macrophages.

Author

Wang, Xingqi, Gou, Lingshan, Gao, Yuzhi, Huang, Yuqing, Kuai, Rui, Li, Yu, Wang, Yujing, Chen, Yanhong, Li, Jun, Cheng, Chao, Feng, Zhaojun, Wu, Xuefeng, and Yao, Ruiqin

Subjects
*SECRETION, *INFLAMMATION, *WESTERN immunoblotting, *SMALL molecules, *MOLECULAR dynamics
Abstract

• RalA inhibits IL-1β/IL-18 secretion in levornidazole-treated THP-1 macrophages. • Small molecule levornidazole can directly bind with RalA. • The conformation of RalA might be regulated by levornidazole. • RalA/levornidazole blocks the assembly of NLRP3/ASC/pro-caspase-1 complex. • A novel biological function of RalA in inflammatory responses was discovered. The NLRP3 inflammasome is an important mediator of inflammatory responses and its regulation is an active area of research. RalA is a Ras-like GTPase, which play pivotal roles in the biology of cells. So far, there have been very few studies on RalA regulating inflammatory responses. Bioinformatics analysis predicted that RalA might participate in the regulatory network of NLRP3 inflammasome, which has been confirmed in THP-1 macrophages. After virtual screening of compounds, it was found that levonidazole selected from our virtual small molecule compound library has the potential to bind to RalA. Of note, the interaction of RalA/levornidazole was verified by Surface Plasmon Resonance-Biacore T200, LC/MS analysis and Western blotting analysis. Molecular dynamics simulations revealed that the conformational changes of RalA might be regulated by levornidazole. Additionally, IL-1β/IL-18 secretion from ATP + LPS stimulated THP-1-derived macrophages was RalA-dependently suppressed by levornidazole, suggesting that RalA might have an inhibitory effect on NLRP3 inflammasome activation. The results of co-immunoprecipitation and RalA depletion experiments showed that levornidazole could induce RalA to block the assembly of NLRP3/ASC/pro-caspase-1 complex, thereby reducing the levels of cleaved-caspase-1 and IL-1β/IL-18 secretion. Our study has suggested an anti-inflammatory function of RalA and identified its targeting chemical compound. Overall, this study clarifies a novel pharmacological mechanism by which RalA/levornidazole inhibits NLRP3 inflammasome activation and IL-1β/IL-18 secretion. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

25. Single-Dose Physically Cross-Linked Hyaluronic Acid and Lipid Hybrid Nanoparticles Containing Cyclic Guanosine Monophosphate-Adenosine Monophosphate Eliminate Established Tumors.

Author

Yu J, Li X, Li J, Sun N, Cheng P, Huang J, Li S, and Kuai R

Subjects
Animals, Mice, Lipids chemistry, Mice, Inbred C57BL, Female, Humans, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents pharmacokinetics, Cell Line, Tumor, Hyaluronic Acid chemistry, Nanoparticles chemistry, Nucleotides, Cyclic chemistry
Abstract

Activating the STING pathway in the cytosol of tumor-infiltrating antigen-presenting cells (APCs) represents a promising strategy to elicit potent antitumor immune responses for cancer therapy. However, STING agonists are mostly small hydrophilic molecules that suffer from rapid clearance and poor cytosolic delivery following systemic administration. While various nanoparticles have been developed to promote cytosolic delivery, they often exhibit premature drug release during circulation. Alternatively, stable nanoparticles with sustained release during circulation have poor cytosolic delivery. In this study, we have developed physically cross-linked hyaluronic acid (HA) and lipid hybrid nanoparticles containing cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), denoted as HLHC, to address these challenges. The HLH delivery system has sustained drug release due to multiple lipid layers physically cross-linked by HA. HLHC efficiently delivers cGAMP to the cytosol of APCs, inducing more IFNβ than cGAMP and liposomal cGAMP. HLH also improves the drug circulation time and biodistribution to the tumor compared with the liposomal formulation and free drug. Strikingly, a single dose of HLHC, but not liposomal cGAMP or free cGAMP, elicits potent antitumor immunity and regresses established MC38 tumors. A single dose of HLHC even regresses established B16F10 tumors upon combination with αPD-L1. Moreover, cured animals were protected from rechallenge with the same tumor cells. HLHC represents an efficient strategy to address delivery challenges associated with STING agonists and may have broad applications for the delivery of drugs acting in the cytosol.

Published
2024
Full Text
View/download PDF

26. A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors.

Author

Li J, Luo L, He J, Yu J, Li X, Shen X, Zhang J, Li S, Karp JM, and Kuai R

Subjects
Animals, Mice, Humans, Mice, Inbred C57BL, Nanogels chemistry, Cell Line, Tumor, Female, Administration, Inhalation, Lipids chemistry, Lipids administration & dosage, Lung Neoplasms secondary, Lung Neoplasms immunology, Lung Neoplasms drug therapy, Poly I-C administration & dosage
Abstract

Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy to enhance antitumor immunity by promoting type I interferon secretion. Nevertheless, following pulmonary delivery, poly(I:C) suffers from rapid degradation and poor endosomal escape, thus limiting its potency. Inspired by the structure of a virus that utilizes internal viral proteins to tune the loading and cytosolic delivery of viral nucleic acids, we developed a liponanogel (LNG)-based platform to overcome the delivery challenges of poly(I:C). The LNG comprised an anionic polymer hyaluronic acid-based nanogel core coated by a lipid shell, which served as a protective layer to stabilize the nanogel core in the lungs. The nanogel core was protonated within acidic endosomes to enhance the endosomal membrane permeability and cytosolic delivery of poly(I:C). After pulmonary delivery, LNG-poly(I:C) induced 13.7-fold more IFNβ than poly(I:C) alone and two-fold more than poly(I:C) loaded in the state-of-art lipid nanoparticles [LNP-poly(I:C)]. Additionally, LNG-poly(I:C) induced more potent CD8+ T-cell immunity and stronger therapeutic effects than LNP-poly(I:C). The combination of LNG-poly(I:C) and PD-L1 targeting led to regression of established lung metastases. Due to the ease of manufacturing and the high biocompatibility of LNG, pulmonary delivery of LNG may be broadly applicable to the treatment of different lung tumors and may spur the development of innovative strategies for cancer immunotherapy. Significance: Pulmonary delivery of poly(I:C) with a virus-inspired inhalable liponanogel strongly activates cytosolic MDA5 and RIG-I and stimulates antitumor immunity, representing a promising strategy for safe and effective treatment of metastatic lung tumors., (©2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
Full Text
View/download PDF

27. Precise modulation and use of reactive oxygen species for immunotherapy.

Author

Li X, Gao J, Wu C, Wang C, Zhang R, He J, Xia ZJ, Joshi N, Karp JM, and Kuai R

Subjects
Humans, Animals, Neoplasms therapy, Neoplasms immunology, Neoplasms metabolism, Biocompatible Materials chemistry, Reactive Oxygen Species metabolism, Immunotherapy methods
Abstract

Reactive oxygen species (ROS) play an important role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have leveraged this mechanism to precisely modulate ROS levels in target tissues for improving the effectiveness of immunotherapies in infectious diseases, cancer, and autoimmune diseases. Moreover, ROS-responsive biomaterials can trigger the release of immunotherapeutics and provide tunable release kinetics, which can further boost their efficacy. This review will discuss the latest biomaterial-based approaches for both precise modulation of ROS levels and using ROS as a stimulus to control the release kinetics of immunotherapeutics. Finally, we will discuss the existing challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches for immunotherapy, and provide an outlook for future research.

Published
2024
Full Text
View/download PDF

28. Clathrin light chain-conjugated drug delivery for cancer.

Author

Jung S, Jiang L, Zhao J, Shultz LD, Greiner DL, Bae M, Li X, Ordikhani F, Kuai R, Joseph J, Kasinath V, Elmaleh DR, and Abdi R

Abstract

Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)-conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency. Labeled CLCs localized to 4T1 tumors implanted in mice, and conjugation of PTX to CLC enhanced its delivery to these tumors. Treatment of three different mouse models of cancer-melanoma, breast cancer, and lung cancer-with CLC-PTX resulted in significant growth inhibition of both the primary tumor and metastatic lesions, as compared to treatment with free PTX. CLC-PTX treatment caused a marked increase in apoptosis of tumor cells and reduction of tumor angiogenesis. Our data suggested HSP70 as a binding partner for CLC. Our study demonstrates that CLC-based drug-conjugates constitute a novel drug delivery platform that can augment the effects of chemotherapeutics in treating a variety of cancers. Moreover, conjugation of therapeutics with CLC may be used as means by which drugs are delivered specifically to primary tumors and metastatic lesions, thereby prolonging the survival of cancer patients., Competing Interests: All authors declare no conflict of interests., (© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Published
2022
Full Text
View/download PDF

29. Shattering barriers toward clinically meaningful MSC therapies.

Author

Levy O, Kuai R, Siren EMJ, Bhere D, Milton Y, Nissar N, De Biasio M, Heinelt M, Reeve B, Abdi R, Alturki M, Fallatah M, Almalik A, Alhasan AH, Shah K, and Karp JM

Subjects
Batch Cell Culture Techniques methods, Bioreactors, COVID-19, Coronavirus Infections virology, Graft vs Host Disease therapy, Humans, Metabolic Engineering methods, Pandemics, Pneumonia, Viral virology, SARS-CoV-2, Transplant Recipients, Betacoronavirus, Coronavirus Infections therapy, Mesenchymal Stem Cell Transplantation methods, Mesenchymal Stem Cells metabolism, Pneumonia, Viral therapy
Abstract

More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Published
2020
Full Text
View/download PDF

30. High-Density Lipoprotein-Mimicking Nanodiscs for Chemo-immunotherapy against Glioblastoma Multiforme.

Author

Kadiyala P, Li D, Nuñez FM, Altshuler D, Doherty R, Kuai R, Yu M, Kamran N, Edwards M, Moon JJ, Lowenstein PR, Castro MG, and Schwendeman A

Subjects
Animals, Cell Line, Tumor, Cell Proliferation drug effects, Docetaxel chemistry, Docetaxel therapeutic use, Drug Delivery Systems methods, Female, Flow Cytometry, Humans, Immunohistochemistry, Lomustine chemistry, Lomustine therapeutic use, Mice, Models, Biological, Paclitaxel chemistry, Paclitaxel therapeutic use, Rats, T-Lymphocytes drug effects, T-Lymphocytes metabolism, Glioblastoma drug therapy, Glioblastoma therapy, Immunotherapy methods, Lipoproteins, HDL chemistry, Lipoproteins, HDL therapeutic use
Abstract

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor, for which there is no cure. Treatment effectiveness for GBM has been limited due to tumor heterogeneity, an immunosuppressive tumor microenvironment (TME), and the presence of the blood-brain barrier, which hampers the transport of chemotherapeutic compounds to the central nervous system (CNS). High-density lipoprotein (HDL)-mimicking nanodiscs hold considerable promise to achieve delivery of bioactive compounds into tumors. Herein, we tested the ability of synthetic HDL nanodiscs to deliver chemotherapeutic agents to the GBM microenvironment and elicit tumor regression. To this end, we developed chemo-immunotherapy delivery vehicles based on sHDL nanodiscs loaded with CpG, a Toll-like receptor 9 (TLR9) agonist, together with docetaxel (DTX), a chemotherapeutic agent, for targeting GBM. Our data show that delivery of DTX-sHDL-CpG nanodiscs into the tumor mass elicited tumor regression and antitumor CD8 + T cell responses in the brain TME. We did not observe any overt off-target side effects. Furthermore, the combination of DTX-sHDL-CpG treatment with radiation (IR), which is the standard of care for GBM, resulted in tumor regression and long-term survival in 80% of GBM-bearing animals. Mice remained tumor-free upon tumor cell rechallenge in the contralateral hemisphere, indicating the development of anti-GBM immunological memory. Collectively, these data indicate that sHDL nanodiscs constitute an effective drug delivery platform for the treatment of GBM, resulting in tumor regression, long-term survival, and immunological memory when used in combination with IR. The proposed delivery platform has significant potential for clinical translation.

Published
2019
Full Text
View/download PDF

31. Elimination of established tumors with nanodisc-based combination chemoimmunotherapy.

Author

Kuai R, Yuan W, Son S, Nam J, Xu Y, Fan Y, Schwendeman A, and Moon JJ

Subjects
Animals, Antigens, Neoplasm immunology, Cell Line, Tumor, Disease Models, Animal, Doxorubicin administration & dosage, Doxorubicin chemistry, Drug Carriers, Drug Delivery Systems, Humans, Immunity, Cellular drug effects, Lipoproteins, HDL chemistry, Mice, T-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes metabolism, Treatment Outcome, Tumor Microenvironment drug effects, Tumor Microenvironment immunology, Xenograft Model Antitumor Assays, Antineoplastic Agents administration & dosage, Antineoplastic Agents chemistry, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological chemistry, Nanostructures, Theranostic Nanomedicine methods
Abstract

Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein-mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models. Delivery of DOX via nanodiscs triggered immunogenic cell death of cancer cells and exerted antitumor efficacy without any overt off-target side effects. "Priming" tumors with DOX-carrying nanodiscs elicited robust antitumor CD8 + T cell responses while broadening their epitope recognition to tumor-associated antigens, neoantigens, and intact whole tumor cells. Combination chemoimmunotherapy with nanodiscs plus anti-programmed death 1 therapy induced complete regression of established CT26 and MC38 colon carcinoma tumors in 80 to 88% of animals and protected survivors against tumor recurrence. Our work provides a new, generalizable framework for using nanoparticle-based chemotherapy to initiate antitumor immunity and sensitize tumors to immune checkpoint blockade.

Published
2018
Full Text
View/download PDF

32. Subcutaneous Nanodisc Vaccination with Neoantigens for Combination Cancer Immunotherapy.

Author

Kuai R, Sun X, Yuan W, Xu Y, Schwendeman A, and Moon JJ

Subjects
Adjuvants, Immunologic therapeutic use, Animals, Antigens, Neoplasm therapeutic use, Cancer Vaccines therapeutic use, Injections, Intramuscular, Injections, Subcutaneous, Melanoma, Experimental immunology, Melanoma, Experimental prevention & control, Mice, Mice, Inbred C57BL, Nanostructures therapeutic use, Neoplasms immunology, Adjuvants, Immunologic administration & dosage, Antigens, Neoplasm administration & dosage, Cancer Vaccines administration & dosage, Immunotherapy methods, Nanostructures administration & dosage, Neoplasms therapy, Vaccination methods
Abstract

While cancer immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors. We report that nanodiscs administered via the subcutaneous (SC) or intramuscular (IM) routes were well tolerated in mice without any signs of toxicity. The SC route significantly enhanced nanoparticle delivery to draining lymph nodes, improved nanodisc uptake by antigen-presenting cells, and generated 7-fold higher frequency of neoantigen-specific T cells, compared with the IM route. Importantly, when mice bearing advanced B16F10 melanoma tumors were treated with nanodiscs plus anti-PD-1 and anti-CTLA-4 IgG therapy, the combination immunotherapy exerted potent antitumor efficacy, leading to eradication of established tumors in ∼60% of animals. These results demonstrate nanodiscs customized with patient-specific tumor neoepitopes as a safe and powerful vaccine platform for immunotherapy against advanced cancer.

Published
2018
Full Text
View/download PDF

33. Synthetic High-Density Lipoprotein-Mediated Targeted Delivery of Liver X Receptors Agonist Promotes Atherosclerosis Regression.

Author

Guo Y, Yuan W, Yu B, Kuai R, Hu W, Morin EE, Garcia-Barrio MT, Zhang J, Moon JJ, Schwendeman A, and Eugene Chen Y

Subjects
Animals, Atherosclerosis pathology, Cell Line, Hydrocarbons, Fluorinated pharmacology, Hydrocarbons, Fluorinated therapeutic use, Lipogenesis, Liver pathology, Mice, Inbred C57BL, Models, Biological, Nanoparticles chemistry, Nanoparticles ultrastructure, Plaque, Atherosclerotic drug therapy, Plaque, Atherosclerotic pathology, Sulfonamides pharmacology, Sulfonamides therapeutic use, Atherosclerosis drug therapy, Drug Delivery Systems, Lipoproteins, HDL metabolism, Liver X Receptors agonists
Abstract

Targeting at enhancing reverse cholesterol transport (RCT) is apromising strategy for treating atherosclerosis via infusion of reconstitute high density lipoprotein (HDL) as cholesterol acceptors or increase of cholesterol efflux by activation of macrophage liver X receptors (LXRs). However, systemic activation of LXRs triggers excessive lipogenesis in the liver and infusion of HDL downregulates cholesterol efflux from macrophages. Here we describe an enlightened strategy using phospholipid reconstituted apoA-I peptide (22A)-derived synthetic HDL (sHDL) to deliver LXR agonists to the atheroma and examine their effect on atherosclerosis regression in vivo. A synthetic LXR agonist, T0901317 (T1317) was encapsulated in sHDL nanoparticles (sHDL-T1317). Similar to the T1317 compound, the sHDL-T1317 nanoparticles upregulated the expression of ATP-binding cassette transporters and increased cholesterol efflux in macrophages in vitro and in vivo. The sHDL nanoparticles accumulated in the atherosclerotic plaques of ApoE-deficient mice. Moreover, a 6-week low-dose LXR agonist-sHDL treatment induced atherosclerosis regression while avoiding lipid accumulation in the liver. These findings identify LXR agonist loaded sHDL nanoparticles as a promising therapeutic approach to treat atherosclerosis by targeting RCT in a multifaceted manner: sHDL itself serving as both a drug carrier and cholesterol acceptor and the LXR agonist mediating upregulation of ABC transporters in the aorta., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2018
Full Text
View/download PDF

34. Immunogenic Cell Death Amplified by Co-localized Adjuvant Delivery for Cancer Immunotherapy.

Author

Fan Y, Kuai R, Xu Y, Ochyl LJ, Irvine DJ, and Moon JJ

Subjects
Animals, CD8-Positive T-Lymphocytes immunology, Cancer Vaccines immunology, Cell Death, Cell Line, Tumor, Colonic Neoplasms immunology, Colonic Neoplasms pathology, Dendritic Cells immunology, Humans, Melanoma, Experimental immunology, Melanoma, Experimental pathology, Mice, Mice, Inbred BALB C, Nanoparticles, Neoplasm Transplantation, Particle Size, T-Lymphocytes, Cytotoxic immunology, Adjuvants, Immunologic therapeutic use, Cancer Vaccines therapeutic use, Colonic Neoplasms therapy, Immunotherapy methods, Melanoma, Experimental therapy
Abstract

Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have indicated that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate antitumor immune responses. However, it remains unclear how to exploit ICD for cancer immunotherapy. Here, we present a new material-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their therapeutic potential in murine models of melanoma and colon carcinoma. We have generated immunogenically dying tumor cells surface-modified with adjuvant-loaded nanoparticles. Dying tumor cells laden with adjuvant nanodepots efficiently promote activation and antigen cross-presentation by dendritic cells in vitro and elicit robust antigen-specific CD8α + T-cells in vivo. Furthermore, whole tumor-cell vaccination combined with immune checkpoint blockade leads to complete tumor regression in ∼78% of CT26 tumor-bearing mice and establishes long-term immunity against tumor recurrence. Our strategy presented here may open new doors to "personalized" cancer immunotherapy tailored to individual patient's tumor cells.

Published
2017
Full Text
View/download PDF

35. Synthetic high-density lipoprotein nanodisks for targeted withalongolide delivery to adrenocortical carcinoma.

Author

Kuai R, Subramanian C, White PT, Timmermann BN, Moon JJ, Cohen MS, and Schwendeman A

Subjects
Adrenal Cortex Neoplasms metabolism, Adrenocortical Carcinoma metabolism, Animals, Antineoplastic Agents pharmacokinetics, Apolipoprotein A-I chemistry, Biological Transport, Cell Line, Tumor, Cholesterol metabolism, Half-Life, Humans, Lipoproteins, HDL chemistry, Mice, Nude, Nanostructures chemistry, Particle Size, Peptides chemistry, Peptides metabolism, Scavenger Receptors, Class B metabolism, Xenograft Model Antitumor Assays, Adrenal Cortex Neoplasms drug therapy, Adrenocortical Carcinoma drug therapy, Antineoplastic Agents administration & dosage, Drug Delivery Systems methods, Nanostructures administration & dosage, Withanolides administration & dosage
Abstract

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs), which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative - withalongolide A 4,19,27-triacetate (WGA-TA) - which has shown potent antitumor efficacy, but poor aqueous solubility. Our strategy was to use synthetic HDL (sHDL) nanodisks, which are effective in tumor-targeted delivery due to their smallness, long circulation half-life, documented safety, and ability to bind to SRB1. In this study, we prepared sHDL nanodisks using an optimized phospholipid composition combined with ApoA 1 mimetic peptide (22A), which has previously been tested in clinical trials, to load WGA-TA. Following optimization, WGA-TA nanodisks showed drug encapsulation efficiency of 78%, a narrow particle size distribution (9.81±0.41 nm), discoid shape, and sustained drug release in phosphate buffered saline. WGA-TA-sHDL nanodisks exhibited higher cytotoxicity in the ACC cell line H295R half maximal inhibitory concentration ([IC 50 ] 0.26±0.045 μM) than free WGA-TA (IC 50 0.492±0.115 μM, P <0.05). Fluorescent dye-loaded sHDL nanodisks efficiently accumulated in H295R adrenal carcinoma xenografts 24 hours following dosing. Moreover, daily intraperitoneal administration of 7 mg/kg WGA-TA-loaded sHDL nanodisks significantly inhibited tumor growth during 21-day administration to H295R xenograft-bearing mice compared to placebo ( P <0.01). Collectively, these results suggest that WGA-TA-loaded nanodisks may represent a novel and beneficial therapeutic strategy for the treatment of ACC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Published
2017
Full Text
View/download PDF

36. Designer vaccine nanodiscs for personalized cancer immunotherapy.

Author

Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, and Moon JJ

Subjects
Animals, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes pathology, Cell Line, Tumor, Female, Humans, Immunity, Cellular drug effects, Mice, Antigens, Neoplasm chemistry, Antigens, Neoplasm immunology, Antigens, Neoplasm pharmacology, Cancer Vaccines chemistry, Cancer Vaccines immunology, Cancer Vaccines pharmacology, Epitopes chemistry, Epitopes immunology, Epitopes pharmacology, Nanostructures chemistry, Nanostructures therapeutic use, Neoplasms, Experimental immunology, Neoplasms, Experimental pathology, Neoplasms, Experimental therapy, Vaccination
Abstract

Despite the tremendous potential of peptide-based cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α + cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells. Strikingly, nanodiscs elicited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials (that is, CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumour growth. Nanodiscs eliminated established MC-38 and B16F10 tumours when combined with anti-PD-1 and anti-CTLA-4 therapy. These findings represent a new powerful approach for cancer immunotherapy and suggest a general strategy for personalized nanomedicine.

Published
2017
Full Text
View/download PDF

37. High-Density Lipoproteins: Nature's Multifunctional Nanoparticles.

Author

Kuai R, Li D, Chen YE, Moon JJ, and Schwendeman A

Subjects
Animals, Apolipoprotein A-I chemistry, Apolipoprotein A-I metabolism, Apolipoprotein A-I pharmacokinetics, Drug Carriers metabolism, Drug Carriers pharmacokinetics, Drug Delivery Systems methods, Humans, Lipoproteins, HDL metabolism, Lipoproteins, HDL pharmacokinetics, Nanomedicine methods, Nanoparticles analysis, Nanoparticles metabolism, Recombinant Proteins chemistry, Recombinant Proteins metabolism, Recombinant Proteins pharmacokinetics, Drug Carriers chemistry, Lipoproteins, HDL chemistry, Nanoparticles chemistry
Abstract

High-density lipoproteins (HDL) are endogenous nanoparticles involved in the transport and metabolism of cholesterol, phospholipids, and triglycerides. HDL is well-known as the "good" cholesterol because it not only removes excess cholesterol from atherosclerotic plaques but also has anti-inflammatory and antioxidative properties, which protect the cardiovascular system. Circulating HDL also transports endogenous proteins, vitamins, hormones, and microRNA to various organs. Compared with other synthetic nanocarriers, such as liposomes, micelles, and inorganic and polymeric nanoparticles, HDL has unique features that allow them to deliver cargo to specific targets more efficiently. These attributes include their ultrasmall size (8-12 nm in diameter), high tolerability in humans (up to 8 g of protein per infusion), long circulating half-life (12-24 h), and intrinsic targeting properties to different recipient cells. Various recombinant ApoA proteins and ApoA mimetic peptides have been recently developed for the preparation of reconstituted HDL that exhibits properties similar to those of endogenous HDL and has a potential for industrial scale-up. In this review, we will summarize (a) clinical pharmacokinetics and safety of reconstituted HDL products, (b) comparison of HDL with inorganic and other organic nanoparticles,, ((c) the rationale for using HDL as drug delivery vehicles for important therapeutic indications, (d) the current state-of-the-art in HDL production, and (e) HDL-based drug delivery strategies for small molecules, peptides/proteins, nucleic acids, and imaging agents targeted to various organs.)

Published
2016
Full Text
View/download PDF

38. Increased delivery of doxorubicin into tumor cells using extracellularly activated TAT functionalized liposomes: in vitro and in vivo study.

Author

Yuan W, Kuai R, Ran R, Fu L, Yang Y, Qin Y, Liu Y, Tang J, Fu H, Zhang Q, Yuan M, Zhang Z, Gao F, and He Q

Subjects
Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cell Line, Tumor, Cell Survival drug effects, Cell-Penetrating Peptides chemistry, Doxorubicin chemistry, Doxorubicin pharmacology, Drug Screening Assays, Antitumor, Drug Stability, Liposomes chemistry, Liposomes pharmacology, Male, Mice, Mice, Inbred BALB C, Polyethylene Glycols chemistry, Tissue Distribution, Antineoplastic Agents pharmacokinetics, Cell-Penetrating Peptides pharmacokinetics, Doxorubicin pharmacokinetics, Liposomes pharmacokinetics
Abstract

The development of highly efficient tumor-targeted delivery systems is crucial for successful tumor treatment. Previously, a novel cell-penetrating peptide TAT and cleavable polyethylene glycol (PEG) co-modified liposome delivery system (C-TAT-Lipo) showed enhanced accumulation in tumor regions. Under the control of cysteine (Cys), the liposomes were activated extracellularly and achieved increased delivery of their cargo into tumor cells efficiently. In this study, we developed an optimal formulation for the encapsulation of Doxorubicin (DOX) by this delivery system for tumor treatment. The in vitro study showed that the C-TAT-Lipo with Cys delivery system not only enhanced the amount of DOX delivered by at least 100% compared to other DOX-containing formulations, but also displayed high cytotoxicity against tumorigenic cell lines. Compared to other groups, the DOX-loaded C-TAT-Lipo formulation in the presence of cysteine enhanced treatment efficacy by lowering the IC50 (1.67 +/- 0.14 microM) and increasing the cancer cell apoptosis percentage (37.10%). Moreover, the in vivo antitumor activity also showed that DOX-loaded C-TAT-Lipo with injection of cysteine achieved the best tumor growth inhibition with a tumor growth rate of only 58.40 +/- 16.33% (% of initial volume/day), which was significant less than that achieved by other DOX formulations.

Published
2014
Full Text
View/download PDF

39. Targeted delivery of cargoes into a murine solid tumor by a cell-penetrating peptide and cleavable poly(ethylene glycol) comodified liposomal delivery system via systemic administration.

Author

Kuai R, Yuan W, Li W, Qin Y, Tang J, Yuan M, Fu L, Ran R, Zhang Z, and He Q

Subjects
Animals, Cell Line, Tumor, Cell-Penetrating Peptides genetics, Disease Models, Animal, Drug Carriers chemistry, Drug Stability, Fluorescent Dyes chemistry, Gene Products, tat genetics, Injections, Intravenous, Male, Mice, Mice, Inbred BALB C, Molecular Structure, Antineoplastic Agents pharmacology, Cell-Penetrating Peptides chemistry, Drug Delivery Systems, Gene Products, tat chemistry, Liposomes chemistry, Neoplasms drug therapy, Polyethylene Glycols chemistry
Abstract

A liposomal delivery system with a high efficiency of accumulation in tumor tissue and then transportation of the cargo into tumor cells was developed here and evaluated via systemic administration. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)(2000) (DSPE-PEG(2000))-TAT and protective DSPE-PEG(2000) modified liposomes possessing good stability in 50% FBS (fetal bovine serum) and good uptake efficiency were used as the basic formulation (TAT-SL; SL = stealth liposome), and then longer cysteine (Cys)-cleavable PEG(5000) was incorporated to modulate the function of TAT. All of the formulations to be used in vivo had sizes in a range of 80-100 nm and were stable in the presence of 50% FBS. Optical imaging showed that the incorporation of cleavable PEG(5000) into TAT-SL (i.e., C-TAT-SL) led to much more tumor accumulation and much less liver distribution compared with TAT-SL. The in vivo delivery profiles of C-TAT-SL were investigated using DiD as a fluorescent probe. Confocal laser scanning microscopy and flow cytometry showed that C-TAT-SL had a 48% higher (p < 0.001) delivery efficiency in the absence of Cys and a 130% higher (p < 0.001) delivery efficiency in the presence of Cys than the control (SL), indicating the successful targeted delivery of cargo was achieved by C-TAT-SL via systemic administration especially with a subsequent administration of Cys.

Published
2011
Full Text
View/download PDF

40. Efficient delivery of payload into tumor cells in a controlled manner by TAT and thiolytic cleavable PEG co-modified liposomes.

Author

Kuai R, Yuan W, Qin Y, Chen H, Tang J, Yuan M, Zhang Z, and He Q

Subjects
Amino Acid Sequence, Animals, Biological Transport, Active, Cell Line, Tumor, Cell-Penetrating Peptides chemistry, Drug Stability, Gene Products, tat chemistry, Hep G2 Cells, Humans, Liposomes chemistry, Mice, Neoplasms, Experimental drug therapy, Neoplasms, Experimental metabolism, Polyethylene Glycols chemistry, Cell-Penetrating Peptides administration & dosage, Drug Delivery Systems, Gene Products, tat administration & dosage, Liposomes administration & dosage
Abstract

Recently, PEGylation has been extensively employed to increase the circulation time of liposomes and enhance their accumulation in tumor tissue via the enhanced permeability and retention (EPR) effect; however, poly(ethylene glycol) (PEG) is unfavorable for the uptake of liposomes by tumor cells because of its steric hindrance. In this study, thiolytic cleavable PEG modified liposomes were used to solve this dilemma. Before arrival at the tumor tissue, PEG presents on the surface of liposomes, which is useful for passive accumulation in tumor tissue. Upon reaching the tumor tissues, the PEG chain could be removed by a safe cleaving reagent l-cysteine (l-Cys), and thus, the steric hindrance of PEG could be overcome conveniently. To further improve the uptake of liposomes, a "functional molecule" cell-penetrating peptide TAT was attached to the distal end of a shorter PEG spacer anchored to the surface of the liposomes, which could be shielded by cleavable PEG during circulation; upon arriving at tumor tissue, PEG was removed and thus the "functional molecule" TAT was exposed, and then TAT could mediate the uptake of the liposomes with high efficiency. In this study, thiolytic cleavable PEG was synthesized via a disulfide bridge, DOPE-PEG(1600)-TAT was synthesized by sulfhydryl-maleimide reaction, and then Rh-PE labeled liposomes composed of 2% DOPE-PEG(1600)-TAT and various amounts of cleavable PEG(5000) (2%, 4%, and 8%) were prepared, with particle size around 100 nm and slightly negative charge. These liposomes showed good stability in the presence of 10% serum. Their uptake by tumor cells HepG2 in vitro was assessed qualitatively and quantitatively. Liposomes modified with 2% DOPE-PEG(1600)-TAT and 8% DOPE-S-S-mPEG(5000) were regarded as the optimal formulation. In this preparation, nearly no uptake could be observed before addition of l-Cys, which meant undesired uptake during circulation could be avoided, while the uptake upon addition of l-Cys was 4 times as high as that in the absence of l-Cys. For the uptake in vivo, calcein loaded and Rh-PE labeled 8% cleavable PEG + 2% TAT modified liposomes were injected intratumorally into H22 tumor bearing mice. Confocal laser scanning microscopy (CLSM) showed that the uptake of 8% cleavable PEG + 2% TAT modified liposomes was much higher than that of 8% noncleavable PEG + 2% TAT modified liposomes in the presence of l-Cys. Thus, tumor targeted delivery could be achieved efficiently by the liposomal drug delivery system developed here in a controlled manner.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results