AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Targeted drug delivery coupled with rapid drug release in cytoplasm is a powerful strategy to enhance efficacy and reduce off-target effects of anti-cancer drugs. Herein, we describe a dual-functional mixed micellar system consisting of a pH-responsive copolymer D-α-tocopheryl polyethylene glycol 1000-blockpoly-(β-amino ester) (TPGS-b-PBAE, TP) and AS1411 aptamer (Apt) decorated TPGS polymer (Apt-TPGS), which recognizes the over-expressed nucleolin on the plasma membrane of cancer cells. The anti-cancer drug paclitaxel (PTX) was encapsulated in the Apt-mixed micelles, and these drug-loaded micelles had a suitable particle size and zeta potential of 116.3 nm ± 12.4 nm and -26.2 mV ±4.2 mV, respectively. PTX/Apt-mixed micelles were stable at pH 7.4, but they dissociated and quickly released the encapsulated PTX in a weakly acidic environment (pH 5.5). Compared with non-Apt modified mixed micelles, more Apt-modified mixed micelles were internalized in SKOV3 ovarian cancer cells, whereas no significant difference in cellular uptake was observed in normal cells (LO2 cells). The enhanced transmembrane ability of Apt-modified mixed micelles was achieved through Apt-nucleolin interaction. With a synergistic effect of cancer cell recognition and pH-sensitive drug release, we observed significantly increased cytotoxicity and G2/M phase arrest against SKOV3 cells by PTX/Apt-mixed micelles. Intravenous administration of PTX/Apt-mixed micelles for 16 days significantly increased tumor accumulation of PTX, inhibited tumor growth, and reduced myelosuppression on tumor-bearing mice compared with free PTX injection. Therefore, this dual-functional Apt-mixed micellar system is a promising drug delivery system for targeted cancer therapy.
Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2012. CA: Cancer J. Clin. 2012, 62, 10-29.
Kumar, S.; Mahdi, H.; Bryant, C.; Shah, J. P.; Garg, G.; Munkarah, A. Clinical trials and progress with paclitaxel in ovarian cancer. Int. J. Women's. Health 2010, 2, 411-427.
Zhang, Z. P.; Mei, L.; Feng, S. S. Paclitaxel drug delivery systems. Expert Opin. Drug Delivery 2013, 10, 325-340.
Torne, S. J.; Ansari, K. A.; Vavia, P. R.; Trotta, F.; Cavalli, R. Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded nanosponges. Drug Delivery 2010, 17, 419-425.
Paál, K.; Müller, J.; Hegedûs, L. High affinity binding of paclitaxel to human serum albumin. Eur. J. Biochem. 2001, 268, 2187-2191.
Weiss, R. B.; Donehower, R.; Wiernik, P.; Ohnuma, T.; Gralla, R.; Trump, D.; Baker, J.; Van Echo, D.; Von Hoff, D.; Leyland-Jones, B. Hypersensitivity reactions from taxol. J. Clin. Oncol. 1990, 8, 1263-1268.
Szebeni, J.; Alving, C. R.; Muggia, F. M. Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: An in vitro study. J. Natl. Cancer Inst. 1998, 90, 300-306.
Scripture, C. D.; Figg, W. D.; Sparreboom, A. Paclitaxel chemotherapy: From empiricism to a mechanism-based formulation strategy. Ther. Clin. Risk Manag. 2005, 1, 107.
Singla, A. K.; Garg, A.; Aggarwal, D. Paclitaxel and its formulations. Int. J. Pharm. 2002, 235, 179-192.
Nakamura, T.; Akita, H.; Yamada, Y.; Hatakeyama, H.; Harashima, H. A multifunctional envelope-type nanodevice for use in nanomedicine: Concept and applications. Acc. Chem. Res. 2012, 45, 1113-1121.
Xing, R. J.; Bhirde, A. A.; Wang, S. J.; Sun, X. L.; Liu, G.; Hou, Y. L.; Chen, X. Y. Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles. Nano Res. 2013, 6, 1-9.
Liu, S. Y.; Chang, C. N.; Verma, M. S.; Hileeto, D.; Muntz, A.; Stahl, U.; Woods, J.; Jones, L. W.; Gu, F. X. Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentally-induced dry eye syndrome. Nano Res. in press, DOI: 10.1007/s12274-014-0547-3.
Zhang, L.; Wang, W.; Jiang, D.; Gao, E.; Sun, S. Photoreduction of CO2 on BiOCl nanoplates with the assistance of photoinduced oxygen vacancies. Nano Res. in press, DOI: 10.1007/s12274-014-0564-2.
Ma, P.; Mumper, R. J. Paclitaxel nano-delivery systems: A comprehensive review. J. Nanomed. Nanotechnol. 2013, 4, 1000164.
Kamaly, N.; Xiao, Z.; Valencia, P. M.; Radovic-Moreno, A. F.; Farokhzad, O. C. Targeted polymeric therapeutic nanoparticles: Design, development and clinical translation. Chem. Soc. Rev. 2012, 41, 2971-3010.
Deng, C.; Jiang, Y.; Cheng, R.; Meng, F.; Zhong, Z. Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: Promises, progress and prospects. Nano Today 2012, 7, 467-480.
Shen, M.; Huang, Y.; Han, L.; Qin, J.; Fang, X.; Wang, J.; Yang, V. C. Multifunctional drug delivery system for targeting tumor and its acidic microenvironment. J. Control Release 2012, 161, 884-892.
Barbas, A. S.; Mi, J.; Clary, B. M.; White, R. R. Aptamer applications for targeted cancer therapy. Future Oncology 2010, 6, 1117-1126.
Farokhzad, O. C.; Karp, J. M.; Langer, R. Nanoparticle-aptamer bioconjugates for cancer targeting. Expert Opin Drug Deliv. 2006, 3, 311-324.
Bates, P. J.; Laber, D. A.; Miller, D. M.; Thomas, S. D.; Trent, J. O. Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp. Mol. Pathol. 2009, 86, 151-164.
Keefe, A. D.; Pai, S.; Ellington, A. Aptamers as therapeutics. Nat. Rev. Drug Discov. 2010, 9, 537-550.
Ireson, C. R.; Kelland, L. R. Discovery and development of anticancer aptamers. Mol. Cancer Ther. 2006, 5, 2957-2962.
Dapić, V.; Bates, P. J.; Trent, J. O.; Rodger, A.; Thomas, S. D.; Miller, D. M. Antiproliferative activity of G-quartet-forming oligonucleotides with backbone and sugar modifications. Biochemistry 2002, 41, 3676-3685.
Cao, Z.; Tong, R.; Mishra, A.; Xu, W.; Wong, G. C.; Cheng, J.; Lu, Y. Reversible cell-specific drug delivery with aptamer-functionalized liposomes. Angew. Chem. Int. Edit. 2009, 48, 6494-6498.
Guo, J.; Gao, X.; Su, L.; Xia, H.; Gu, G.; Pang, Z.; Jiang, X.; Yao, L.; Chen, J.; Chen, H. Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials 2011, 32, 8010-8020.
Wu, J.; Song, C.; Jiang, C.; Shen, X.; Qiao, Q.; Hu, Y. Nucleolin targeting AS1411 modified protein nanoparticle for antitumor drugs delivery. Mol. Pharm. 2013, 10, 3555-3563.
Aravind, A.; Jeyamohan, P.; Nair, R.; Veeranarayanan, S.; Nagaoka, Y.; Yoshida, Y.; Maekawa, T.; Kumar, D. S. AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery. Biotechnol. Bioeng. 2012, 109, 2920-2931.
Shen, Y.; Tang, H.; Radosz, M.; Van Kirk, E.; Murdoch, W. J. pH-responsive nanoparticles for cancer drug delivery. Methods Mol Biol. 2008, 437, 183-216.
Deng, C.; Jiang, Y. J.; Cheng, R.; Meng, F. H.; Zhong, Z. Y. Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: Promises, progress and prospects. Nano Today 2012, 7, 467-480.
Lee, E. S.; Gao, Z.; Bae, Y. H. Recent progress in tumor pH targeting nanotechnology. J. Control Release 2008, 132, 164-170.
Ganta, S.; Devalapally, H.; Shahiwala, A.; Amiji, M. A review of stimuli-responsive nanocarriers for drug and gene delivery. J. Control Release 2008, 126, 187-204.
Ulbrich, K.; Šubr, V. R. Polymeric anticancer drugs with ph-controlled activation. Adv. Drug Deliv. Rev. 2004, 56, 1023-1050.
Shenoy, D.; Little, S.; Langer, R.; Amiji, M. Poly(ethylene oxide)-modified poly(β-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: Part 2. In vivo distribution and tumor localization studies. Pharm. Res. 2005, 22, 2107-2114.
Devalapally, H.; Shenoy, D.; Little, S.; Langer, R.; Amiji, M. Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: Part 3. Therapeutic efficacy and safety studies in ovarian cancer xenograft model. Cancer Chemother. Pharmacol. 2007, 59, 477-484.
Potineni, A.; Lynn, D. M.; Langer, R.; Amiji, M. M. Poly(ethylene oxide)-modified poly(β-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery. J. Control. Release 2003, 86, 223-234.
Zhao, S.; Tan, S.; Guo, Y.; Huang, J.; Chu, M.; Liu, H.; Zhang, Z. P. pH-sensitive docetaxel-loaded D-α-tocopheryl polyethylene glycol succinate-poly(β-amino ester) copolymer nanoparticles for overcoming multidrug resistance. Biomacromolecules 2013, 14, 2636-2646.
Shen, Y.; Tang, H.; Zhan, Y.; Van Kirk, E. A.; Murdoch, W. J. Degradable poly(β-amino ester) nanoparticles for cancer cytoplasmic drug delivery. Nanomedicine: NBM 2009, 5, 192-201.
Zhang, Z. P.; Tan, S. W.; Feng, S. S. Vitamin E TPGS as a molecular biomaterial for drug delivery. Biomaterials 2012, 33, 4889-4906.
Zhang, J.; Li, Y.; Gao, W.; Repka, M. A.; Wang, Y.; Chen, M. Andrographolide-loaded PLGA-PEG-PLGA micelles to improve its bioavailability and anticancer efficacy. Expert Opin. Drug Deliv. 2014, 11, 1367-1380.
Yin, H.; Lee, E. S.; Kim, D.; Lee, K. H.; Oh, K. T.; Bae, Y. H. Physicochemical characteristics of pH-sensitive poly(L-Histidine)-b-poly(ethylene glycol)/poly(L-Lactide)-b-poly(ethylene glycol) mixed micelles. J. Control Release 2008, 126, 130-138.
Jordan, M. A.; Wilson, L. Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 2004, 4, 253-265.
Bacus, S. S.; Gudkov, A. V.; Lowe, M.; Lyass, L.; Yung, Y.; Komarov, A. P.; Keyomarsi, K.; Yarden, Y.; Seger, R. Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is independent of p53. Oncogene 2001, 20, 147-155.
Zhang, Z.; Feng, S. S. The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. Biomaterials 2006, 27, 4025-4033.
Guo, Y.; Luo, J.; Tan, S.; Otieno, B. O.; Zhang, Z. P.; Tan, S. W.; Feng, S. S. The applications of Vitamin E TPGS in drug delivery. Eur. J. Pharm. Sci. 2013, 49, 175-186.
Wu, J. Statistical inference for tumor growth inhibition T/C ratio. J. Biopharm. Stat. 2010, 20, 954-964.
Crawford, J.; Dale, D. C.; Lyman, G. H. Chemotherapy-induced neutropenia. Cancer 2004, 100, 228-237.
Crowley, K.; Augustin, K. Chemotherapy-induced anemia. U.S. Pharmacist 2003, 28, 04.
Greish, K. Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting. Methods Mol Biol. 2010, 624, 25-37.
Ilium, L.; Davis, S.; Wilson, C.; Thomas, N.; Frier, M.; Hardy, J. Blood clearance and organ deposition of intravenously administered colloidal particles. The effects of particle size, nature and shape. Int. J. Pharm. 1982, 12, 135-146.
Barenholz, Y.; Amselem, S.; Goren, D.; Cohen, R.; Gelvan, D.; Samuni, A.; Golden, E. B.; Gabizon, A. Stability of liposomal doxorubicin formulations: Problems and prospects. Med. Res. Rev. 1993, 13, 449-491.
Zhang, L.; Yang, M.; Wang, Q.; Li, Y.; Guo, R.; Jiang, X.; Yang, C.; Liu, B. 10-Hydroxycamptothecin loaded nanoparticles: Preparation and antitumor activity in mice. J. Control. Release 2007, 119, 153-162.
