AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Developing multifunctional nanoparticles to support new therapy models is a promising and challenging task to address the current dilemma on antitumor treatment. Herein, we incorporated multifunctional dendritic nanoparticles into a poly(D, L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers thermosensitive injectable hydrogel matrix to construct a localized drug delivery system for combining chemotherapy and immunotherapy. The multifunctional dendritic nanoparticles were designed with following expectations: i, Dendritic scaffolds provide a hydrophobic interior to load the anticancer drug, doxorubicin (DOX), for chemotherapy; and ii, dendritic scaffolds are used to build arginine-rich molecules to provide the inducible nitric oxide synthase (iNOS) substrate, L-Arg, to M1 macrophages, which can produce the cytotoxic substance nitric oxide (NO) and subsequently induce tumor cell destruction through immunotherapy. It is noteworthy that the dendritic nanoparticles-in-hydrogel delivery system is able to gel at physiological temperature and serves as a warehouse for the sustained release of the drug. Ultimately, this system showed great efficacy in treating 4T1 cells-xenografted BALB/C mice (86.62% tumor growth inhibition). Therefore, this localized drug delivery system combining chemotherapy and immunotherapy provides a novel approach for cancer therapy.
Jain, R. K. Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat. Med. 2001, 7, 987–989.
Zhang, W. Q.; Tung, C. H. Cisplatin crosslinked multifunctional nanodrugplexes for combination therapy. ACS Appl. Mater. Interfaces 2017, 9, 8547–8555.
Fan, L.; Jin, B. Q.; Zhang, S. L.; Song, C. J.; Li, Q. Stimulifree programmable drug release for combination chemotherapy. Nanoscale 2016, 8, 12553–12559.
Syrios, J.; Banerjee, S.; Kaye, S. B. Advanced epithelial ovarian cancer: From standard chemotherapy to promising molecular pathway targets—Where are we now? Anticancer Res. 2014, 34, 2069–2077.
Conroy, T.; Desseigne, F.; Ychou, M.; Bouché, O.; Guimbaud, R.; Bécouarn, Y.; Adenis, A.; Raoul, J. L.; Gourgou-Bourgade, S.; de la Fouchardière, C. et al. Folfirinox versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 2011, 364, 1817–1825.
Mekuria, S. L.; Debele, T. A.; Chou, H. Y.; Tsai, H. C. IL-6 antibody and RGD peptide conjugated poly(amidoamine) dendrimer for targeted drug delivery of HeLa cells. J. Phys. Chem. B 2016, 120, 123–130.
Wang, Y.; Cao, X. Y.; Guo, R.; Shen, M. W.; Zhang, M. E.; Zhu, M. F.; Shi, X. Y. Targeted delivery of doxorubicin into cancer cells using a folic acid–dendrimer conjugate. Polym. Chem. 2011, 2, 1754–1760.
Li, Y. K.; Li, Y. C.; Zhang, X.; Xu, X. H.; Zhang, Z. J.; Hu, C.; He, Y. Y.; Gu, Z. W. Supramolecular PEGylated dendritic systems as pH/redox dual-responsive theranostic nanoplatforms for platinum drug delivery and NIR imaging. Theranostics 2016, 6, 1293–1305.
Dalgleish, A. G. Rationale for combining immunotherapy with chemotherapy. Immunotherapy 2015, 7, 309–316.
Zheng, M. B.; Yue, C. X.; Ma, Y. F.; Gong, P.; Zhao, P. F.; Zheng, C. F.; Sheng, Z. H.; Zhang, P. F.; Wang, Z. H.; Cai, L. T. Single-step assembly of DOX/ICG loaded lipidpolymer nanoparticles for highly effective chemo-photothermal combination therapy. ACS Nano 2013, 7, 2056–2067.
He, C. B.; Duan, X. P.; Guo, N. N.; Chan, C.; Poon, C.; Weichselbaum, R. R.; Lin, W. B. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy. Nat. Commun. 2016, 7, 12499.
Tang, W.; Yang, J. B.; Yuan, Y.; Zhao, Z. B.; Lian, Z. X.; Liang, G. L. Paclitaxel nanoparticle awakens immune system to fight against cancer. Nanoscale 2017, 9, 6529–6536.
Yu, S. J.; Zhang, D. L.; He, C. L.; Sun, W. J.; Cao, R. J.; Cui, S. S.; Deng, M. X.; Gu, Z.; Chen, X. S. Injectable thermosensitive polypeptide-based CDDP-complexed hydrogel for improving localized antitumor efficacy. Biomacromolecules 2017, 18, 4341–4348.
Wang, C.; Wang, J. Q.; Zhang, X. D.; Yu, S. J.; Wen, D.; Hu, Q. Y.; Ye, Y. Q.; Bomba, H.; Hu, X. L.; Liu, Z. et al. In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy. Sci. Transl. Med. 2018, 10, eaan3682.
Li, S. Z.; Yang, F.; Ren, X. B. Immunotherapy for hepatocellular carcinoma. Drug Discov. Ther. 2015, 9, 363–371.
Topalian, S. L.; Wolchok, J. D.; Chan, T. A.; Mellman, I.; Palucka, K.; Banchereau, J.; Rosenberg, S. A.; Wittrup, K. D. Immunotherapy: The path to win the war on cancer? Cell 2015, 161, 185–186.
Yang, G.; Wang, J.; Wang, Y.; Li, L.; Guo, X.; Zhou, S. B. An implantable active-targeting micelle-in-nanofiber device for efficient and safe cancer therapy. ACS Nano 2015, 9, 1161–1174.
Formenti, S. C.; Demaria, S. Combining radiotherapy and cancer immunotherapy: A paradigm shift. J. Natl. Cancer Inst. 2013, 105, 256–265.
Andersen, M. H. Immune regulation by self-recognition: Novel possibilities for anticancer immunotherapy. J. Natl. Cancer Inst. 2015, 107, djv154.
Mantovani, A.; Allavena, P. The interaction of anticancer therapies with tumor-associated macrophages. J. Exp. Med. 2015, 212, 435–445.
Sato, T.; Terai, M.; Tamura, Y.; Alexeev, V.; Mastrangelo, M. J.; Selvan, S. R. Interleukin 10 in the tumor microenvironment: A target for anticancer immunotherapy. Immunol. Res. 2011, 51, 170–182.
Franks, H. A.; Wang, Q.; Patel, P. M. New anticancer immunotherapies. Anticancer Res. 2012, 32, 2439–2453.
Kudo, S.; Nagasaki, Y. A novel nitric oxide-based anticancer therapeutics by macrophage-targeted poly(L-arginine)-based nanoparticles. J. Control. Release 2015, 217, 256–262.
Fridman, W. H.; Pagès, F.; Sautès-Fridman, C.; Galon, J. The immune contexture in human tumours: Impact on clinical outcome. Nat. Rev. Cancer 2012, 12, 298–306.
Balkwill, F.; Mantovani, A. Inflammation and cancer: Back to virchow? Lancet 2001, 357, 539–545.
Brown, B. N.; Ratner, B. D.; Goodman, S. B.; Amar, S.; Badylak, S. F. Macrophage polarization: An opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 2012, 33, 3792–3802.
Mantovani, A.; Sozzani, S.; Locati, M.; Allavena, P.; Sica, A. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002, 23, 549–555.
Rath, M.; Müller, I.; Kropf, P.; Closs, E. I.; Munder, M. Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages. Front. Immunol. 2014, 5, 532.
Lechner, M.; Lirk, P.; Rieder, J. Inducible nitric oxide synthase (inos) in tumor biology: The two sides of the same coin. Semin. Cancer Biol. 2005, 15, 277–289.
Salimian, R. B.; Caneba, C.; Nowicka, A.; Nabiyar, A. W.; Liu, X.; Chen, K.; Klopp, A.; Nagrath, D. Nitric oxide mediates metabolic coupling of omentum-derived adipose stroma to ovarian and endometrial cancer cells. Cancer Res. 2015, 75, 456–471.
El-Sehemy, A.; Postovit, L. M.; Fu, Y. X. Nitric oxide signaling in human ovarian cancer: A potential therapeutic target. Nitric Oxide 2016, 54, 30–37.
Engels, K.; Knauer, S. K.; Loibl, S.; Fetz, V.; Harter, P.; Schweitzer, A.; Fisseler-Eckhoff, A.; Kommoss, F.; Hanker, L.; Nekljudova, V. et al. No signaling confers cytoprotectivity through the survivin network in ovarian carcinomas. Cancer Res. 2008, 68, 5159–5166.
Mousa, A. S.; Mousa, S. A. Anti-angiogenesis efficacy of the garlic ingredient alliin and antioxidants: Role of nitric oxide and p53. Nutr. Cancer 2005, 53, 104–110.
Pipilisynetos, E.; Papageorgiou, A.; Sakkoula, E.; Sotiropoulou, G.; Fotsis, T.; Karakiulakis, G.; Maragoudakis, M. E. Inhibition of angiogenesis, tumour growth and metastasis by the no-releasing vasodilators, isosorbide mononitrate and dinitrate. Br. J. Pharmacol. 1995, 116, 1829–1834.
Glasgow, M. D.; Chougule, M. B. Recent developments in active tumor targeted multifunctional nanoparticles for combination chemotherapy in cancer treatment and imaging. J. Biomed. Nanotechnol. 2015, 11, 1859–1898.
Jiang, L.; Li, L.; He, X. D.; Yi, Q. Y.; He, B.; Pan, W. S.; Gu, Z. W. Overcoming drug-resistant lung cancer by paclitaxel loaded dual-functional liposomes with mitochondria targeting and pH-response. Biomaterials 2015, 52, 126–139.
Yi, Q. Y.; Ma, J.; Kang, K.; Gu, Z. W. Dual cellular stimuli-responsive hydrogel nanocapsules for delivery of anticancer drugs. J. Mater. Chem. B 2016, 4, 4922–4933.
Liang, Y.; Gao, W. X.; Peng, X. Y.; Deng, X.; Sun, C. Z.; Wu, H. Y.; He, B. Near infrared light responsive hybrid nanoparticles for synergistic therapy. Biomaterials 2016, 100, 76–90.
Li, N.; Cai, H.; Jiang, L.; Hu, J. N.; Bains, A.; Hu, J.; Gong, Q. Y.; Luo, K.; Gu, Z. W. Enzyme-sensitive and amphiphilic PEGylated dendrimer-paclitaxel prodrug-based nanoparticles for enhanced stability and anticancer efficacy. ACS Appl. Mater. Interfaces 2017, 9, 6865–6877.
Li, Y. C.; Xu, X. H.; Zhang, X.; Li, Y. K.; Zhang, Z. J.; Gu, Z. W. Tumor-specific multiple stimuli-activated dendrimeric nanoassemblies with metabolic blockade surmount chemotherapy resistance. ACS Nano 2017, 11, 416–429.
Jiang, L.; Zhou, S. S.; Zhang, X. K.; Wu, W.; Jiang, X. Q. Dendrimer-based NPs in cancer chemotherapy and genetherapy. Sci. China Mater. , in press, https://doi.rog/10.1007/s40843-018-9242-3.
Guo, C. H.; Sun, L.; Cai, H.; Duan, Z. Y.; Zhang, S. Y.; Gong, Q. Y.; Luo, K.; Gu, Z. W. Gadolinium-labeled biodegradable dendron-hyaluronic acid hybrid and its subsequent application as a safe and efficient magnetic resonance imaging contrast agent. ACS Appl. Mater. Interfaces 2017, 9, 23508–23519.
Elias, P. Z.; Liu, G. W.; Wei, H.; Jensen, M. C.; Horner, P. J.; Pun, S. H. A functionalized, injectable hydrogel for localized drug delivery with tunable thermosensitivity: Synthesis and characterization of physical and toxicological properties. J. Control. Release 2015, 208, 76–84.
Wilhelm, S.; Tavares, A. J.; Dai, Q.; Ohta, S.; Audet, J.; Dvorak, H. F.; Chan, W. C. W. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 2016, 1, 16014.
Ding, D.; Zhu, Z. S.; Li, R. T.; Li, X. L.; Wu, W.; Jiang, X. Q.; Liu, B. R. Nanospheres-incorporated implantable hydrogel as a trans-tissue drug delivery system. ACS Nano 2011, 5, 2520–2534.
Xie, W. S.; Gao, Q.; Guo, Z. H.; Wang, D.; Gao, F.; Wang, X. M.; Wei, Y.; Zhao, L. Y. Injectable and self-healing thermosensitive magnetic hydrogel for asynchronous control release of doxorubicin and docetaxel to treat triple-negative breast cancer. ACS Appl. Mater. Interfaces 2017, 9, 33660– 33673.
Chen, Y. Y.; Wu, H. C.; Sun, J. S.; Dong, G. C.; Wang, T. W. Injectable and thermoresponsive self-assembled nanocomposite hydrogel for long-term anticancer drug delivery. Langmuir 2013, 29, 3721–3729.
Ta, H. T.; Dass, C. R.; Dunstan, D. E. Injectable chitosan hydrogels for localised cancer therapy. J. Control. Release 2008, 126, 205–216.
Ma, H. C.; He, C. L.; Cheng, Y. L.; Li, D. S.; Gong, Y. B.; Liu, J. G.; Tian, H. Y.; Chen, X. S. PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for osteosarcoma treatment. Biomaterials 2014, 35, 8723–8734.
Luo, K.; Li, C. X.; Wang, G.; Nie, Y.; He, B.; Wu, Y.; Gu, Z. W. Peptide dendrimers as efficient and biocompatible gene delivery vectors: Synthesis and in vitro characterization. J. Control. Release 2011, 155, 77–87.
Fu, F. F.; Wu, Y. L.; Zhu, J. Y.; Wen, S. H.; Shen, M. W.; Shi, X. Y. Multifunctional lactobionic acid-modified dendrimers for targeted drug delivery to liver cancer cells: Investigating the role played by PEG spacer. ACS Appl. Mater. Interfaces 2014, 6, 16416–16425.
Al-Jamal, K. T.; Al-Jamal, W. T.; Wang, J. T. W.; Rubio, N.; Buddle, J.; Gathercole, D.; Zloh, M.; Kostarelos, K. Cationic poly-L-lysine dendrimer complexes doxorubicin and delays tumor growth in vitro and in vivo. ACS Nano 2013, 7, 1905–1917.
Svenson, S.; Tomalia, D. A. Dendrimers in biomedical applications-reflections on the field. Adv. Drug. Deliv. Rev. 2005, 57, 2106–2129.
Sun, Q. H.; Sun, X. R.; Ma, X. P.; Zhou, Z. X.; Jin, E. L.; Zhang, B.; Shen, Y. Q.; Van Kirk, E. A.; Murdoch, W. J.; Lott, J. R. et al. Integration of nanoassembly functions for an effective delivery cascade for cancer drugs. Adv. Mater. 2014, 26, 7615–7621.
Zhang, X.; Xu, X. H.; Li, Y. C.; Hu, C.; Zhang, Z. J.; Gu, Z. W. Virion-like membrane-breaking nanoparticles with tumor-activated cell-and-tissue dual-penetration conquer impermeable cancer. Adv. Mater. 2018, 1707240.
Mikucki, M. E.; Fisher, D. T.; Ku, A. W.; Appenheimer, M. M.; Muhitch, J. B.; Evans, S. S. Preconditioning thermal therapy: Flipping the switch on IL-6 for anti-tumour immunity. Int J Hyperth 2013, 29, 464–473.
Guerra, J.; De, Jesus, A.; Santiago-Borrero, P.; Roman-Franco, A.; Rodríguez, E.; Crespo, M. J. Plasma nitric oxide levels used as an indicator of doxorubicin-induced cardiotoxicity in rats. Hematol J 2005, 5, 584–588.
