Main Article Content
Paclitaxel and curcumin have been reported as anti-cancer compounds. Here, we presented a novel combination of paclitaxel and curcumin-loaded PLA-TPGS (PTX-Cur/PLA-TPGS) nanoparticles prepared by a modified solvent extraction/evaporation technique. These nanoparticles were well distributed and stable in water. This combination of paclitaxel and curcumin gave a higher efficiency of both drugs in cytotoxicity, induced apoptosis, and effect on cell cycles of KPL4 cell line in comparison with the use of paclitaxel or curcumin alone or even a normal mixture of these two compounds. Furthermore, PTX-Cur/PLA-TPGS nanoparticles exhibited a powerful ability in preventing MCF7 spheroids growth. Interestingly, curcumin also functioned as both a drug and a label. Based on the autofluorescence of curcumin, the absorption of PTX-Cur/PLA-TPGS nanoparticles into MCF7 spheroids could be followed and calculated. These results suggest that the nanoparticle-combination may provide a promising multifunctional delivery system for anti-cancer drugs.
 D. Gajria, A. Seidman, C. Dang, Adjuvant Taxanes: More to the Story, Clin, Breast Cancer, Vol. 10 Suppl 2, 2010, pp. S41-9, http://doi.org/10.3816/CBC.2010.s.011.
 S. Lee, C. A. Schmitt, Chemotherapy Response and Resistance, Curr, Opin, Genet, Dev, Vol. 13, No. 1, 2003, pp. 6-90, http://doi.org/10.1016/s0959-437x(02)00014-x.
 J. D. Hurt, D. L. Richardson, L. G. Seamon, J. F. Fowler, L. J. Copeland, D. E. Cohn et al., Sustained Progression-free Survival with Weekly Paclitaxel and Bevacizumab in Recurrent Ovarian Cancer, Gynecol, Oncol, Vol. 115, No. 3, 2009,
pp. 396-400, https://doi.org/10.1016/j.ygyno.2009.08.032.
 B. Joe, M. Vijaykumar, B. R. Lokesh, Biological Properties of Curcumin-cellular and Molecular Mechanisms of Action, Crit, Rev, Food Sci, Nutr, Vol. 44, No. 2, 2004, pp. 97-111, http://doi.org/10.1080/10408690490424702.
 H. P. Ammon, M. A. Wahl, Pharmacology of Curcuma Longa, Planta, Med, Vol. 57, No. 1, 1991, pp. 1-7,
 B. B. Aggarwal, C. Sundaram, N. Malani, H. Ichikawa, Curcumin: the Indian Solid Gold, Adv, Exp, Med, Biol, Vol. 595, 2007, pp. 1-75, http://doi.org/10.1007/978-0-387-46401-5-1.
 Q. Liu, W. T. Loo, S. C. Sze, Y. Tong, Curcumin Inhibits Cell Proliferation of MDA-MB-231 and BT-483 Breast Cancer Cells Mediated by Down-regulation of NFkappaB, cyclinD and MMP-1 Transcription, Phytomedicine, Vol. 16, No. 10, 2009, p. 916-22, https://doi.org/10.1016/j.phymed.2009.04.008.
 A. Kunwar, A. Barik, B. Mishra, K. Rathinasamy, R. Pandey, K. I. Priyadarsini, Quantitative Cellular Uptake, Localization and Cytotoxicity of Curcumin in Normal and Tumor Cells, Biochim, Biophys, Acta, Vol. 1780, No. 4, 2008, pp. 9-673, https://doi.org/10.1016/j.bbagen.2007.11.016.
 P. Anand, H. B. Nair, B. Sung, A. B. Kunnumakkara, V. R. Yadav, R. R. Tekmal et al, Design of curcumin-loaded PLGA Nanoparticles Formulation with Enhanced Cellular Uptake, and Increased Bioactivity in Vitro and Superior Bioavailability in Vivo, Biochem, Pharmacol, Vol. 79, No. 3, 2010, pp. 330-8, https://doi.org/10.1016/j.bcp.2009.09.003.
 S. S. Feng, New-concept Chemotherapy by Nanoparticles of Biodegradable Polymers: Where are We Now?, Nanomedicine (Lond), Vol. 1, No. 3, 2006, pp. 297-309, http://doi.org/10.2217/17435822.214.171.1247.
 Z. Zhang, S. S. Feng, Nanoparticles of poly(lactide)/vitamin E TPGS Copolymer for Cancer Chemotherapy: Synthesis, Formulation, Characterization and in Vitro Drug Release, Biomaterials, Vol. 27, No. 2, 2006, p. 262-70, https://doi.org/10.1016/j.biomaterials.2005.05.104.
 S. Ganta, M, Amiji, Coadministration of Paclitaxel and Curcumin in Nanoemulsion Formulations to Overcome Multidrug Resistance in Tumor Cells, Mol, Pharm, Vol. 6, No. 3, 2009, pp. 928-39, https://doi.org/10.1021/mp800240j.
 L. Wei, C. Cai, J. Lin, T. Chen, Dual-drug Delivery System Based on Hydrogel/micelle Composites, Biomaterials, Vol. 30, No. 13, 2009, pp. 2606-13, https://doi.org/10.1016/j.biomaterials.2009.01.006.
 P. T. Ha, T. M. N. Tran, H. D. Pham, Q. H. Nguyen, X. P. Nguyen, The Synthesis of Poly (Lactide)-vitamin E TPGS (PLA-TPGS) Copolymer and Its Utilization to Formulate a Curcumin Nanocarrier, Adv, Nat, Sci: Nanosci, Nanotechnol, Vol. 1, No. 1, 2012, pp. 7, https://doi.org/10.1088/2043-6254/1/1/015012.
 H. N. Nguyen, P. T. Ha, A. S. Nguyen, D. T. Nguyen, H. D. Do, T. Q. Nguyen, T. M. N. Hoang, Curcumin as Fluorescent Probe for Directly Monitoring in Vitro uptake of Curcumin Combined Paclitaxel Loaded PLA-TPGS Nanoparticles, Adv, Nat, Sci: Nanosci, Nanotechnol, Vol. 7, No. 2, 2016, pp. 7, https://doi.org/10.1088/2043-6262/7/2/025001.
 C. Riccardi, I. Nicoletti, Analysis of Apoptosis by Propidium Iodide Staining and Flow Cytometry, Nat, Protoc, Vol. 1, 2006, p. 1458-61, https://doi.org/10.1038/nprot.2006.238.
 J. M. Kelm, N. E. Timmins, C. J. Brown, M. Fussenegger, L. K. Nielsen, Method for Generation of Homogeneous Multicellular Tumor Spheroids Applicable to a Wide Variety of Cell Types, Biotechnol, Bioeng, Vol. 83, No. 2, 2003, p. 173-80, https://doi.org/10.1002/bit.10655.
 M. Vinci, S. Gowan, F. Boxall, L. Patterson, M. Zimmermann, W. Court et al., Advances in Establishment and Analysis of Three-dimensional Tumor Spheroid-based Functional Assays for Target Validation and Drug Evaluation, BMC, Biol, Vol. 10, 2012, pp. 29, https://doi.org/10.1186/1741-7007-10-29.
 S. V. Bava, V. T. Puliappadamba, A. Deepti, A. Nair, D. Karunagaran, R. J. Anto, Sensitization of Taxol-induced Apoptosis by Curcumin Involves Down-regulation of Nuclear Factor-kappaB and the Serine/threonine Kinase Akt and is Independent of Tubulin Polymerization, J. Biol, Chem, Vol. 80, No. 8, 2005, pp. 6301-8, https://doi.org/10.1074/jbc.M410647200.
 V. L. Galic, J. D. Wright, S. N. Lewin, T. J. Herzog, Paclitaxel Poliglumex for Ovarian Cancer, Expert, Opin, Investig, Drugs, Vol. 20, No. 6, 2011, pp. 13-21, https://doi.org/10.1517/13543784.2011.576666.
 M. T. Silva, A. D. Vale, N. M. D. Santos, Secondary Necrosis in Multicellular Animals: an Outcome of Apoptosis with Pathogenic Implications, Apoptosis, Vol. 13, 2008, p. 463-82, https://doi.org/10.1007/s10495-008-0187-8.
 M. V. Blagosklonny, Mitotic Arrest and Cell Fate: Why and How Mitotic Inhibition of Transcription Drives Mutually Exclusive Events, Cell Cycle, Vol. 6, No. 1, 2007, pp.70-4, https://doi.org/10.4161/cc.6.1.3682.
 L. A. K. Schughart, J. P. Freyer, F. Hofstaedter, R. Ebner, The Use of 3-D Cultures for High-throughput Screening: the Multicellular Spheroid Model, J. Biomol, Screen, 2004, pp. 273-85, https://doi.org/10.1177/1087057104265040.
 M. R. Choi, K. J. Stanton-Maxey, J. K. Stanley, C. S. Levin, R. Bardhan, D. Akin et al., A Cellular Trojan Horse for Delivery of Therapeutic Nanoparticles into Tumors, Nano, Lett, Vol. 7, No. 12, 2007, Pp. 3759-65, http://doi.org/10.1021/nl072209.