Co-delivery of Gefitinib and chloroquine by chitosan nanoparticles for overcoming the drug acquired resistance
Tóm tắt
Acquired drug resistance is becoming common during cancer chemotherapy and leads to treatment failure in clinic. To conquer acquired drug resistance, nanotechnology has been employed to deliver drug. In this paper, we prepared chitosan nanoparticles (CS NPs) capable of entrapping Gefitinib and chloroquine (CQ) for multiple drugs combinational therapy. The results showed that Gefitinib/CQ-NPs were characterized of small particle size about 80.8 ± 9.7 nm and positive zeta potential about 21.3 ± 1.56 mV, and drug controlled to release slowly on a biphasic pattern. Compared with free Gefitinib and Gefitinib loaded NPs, Gefitinib and CQ co-delivery by CS nanoparticles showed the higher inhibition rates and enhanced cell apoptosis. Through western blot analysis, we found that Gefitinib could promote LC3 expression, which is the marker of autophagosomes. So, the acquired drug resistance may be associated with autophagy. CQ as an inhibitor of autophagolysosomes formation could overcome autophagy in the resistant cells. These findings demonstrated that chitosan nanoparticles entrapping Gefitinib and chloroquine have the potential to overcome acquired resistance and improve cancer treatment efficacy, especially towards resistant strains.
Tài liệu tham khảo
Petrelli F, Borgonovo K, Cabiddu M, Barni S. Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small-cell lung cancer: a meta-analysis of 13 randomized trials. Clin Lung Cancer. 2012;13:107–14.
Nicholson RI, Gee JMW, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37:9–15.
Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005;353:2012–24.
Levitzki A. Tyrosine kinase inhibitors: views of selectivity, sensitivity, and clinical performance. Annu Rev Pharmacol Toxicol. 2013;53:161–85.
Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011;17:1616–22.
Goldberg SB, Oxnard GR, Digumarthy S, Muzikansky A, Jackman DM, Lennes IT, Sequist LV. Chemotherapy with erlotinib or chemotherapy alone in advanced non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitors. Oncol. 2013;18:1214–20.
Klionsky DJ, Baehrecke EH, Brumell JH, Chu CT, Codogno P, Cuervo AM, Debnath J, Deretic V, Elazar Z, Eskelinen E-L. A comprehensive glossary of autophagy-related molecules and processes. Autophagy. 2011;7:1273–94.
Lieberman AP, Puertollano R, Raben N, Slaugenhaupt S, Walkley SU, Ballabio A. Autophagy in lysosomal storage disorders. Autophagy. 2012;8:719–30.
Levine B, Packer M, Codogno P. Development of autophagy inducers in clinical medicine. J Clin Invest. 2015;125:14–24.
Nihira K, Miki Y, Iida S, Narumi S, Ono K, Iwabuchi E, Ise K, Mori K, Saito M, Ebina M. An activation of LC3A-mediated autophagy contributes to de novo and acquired resistance to EGFR tyrosine kinase inhibitors in lung adenocarcinoma. J Pathol. 2014;234:277–88.
Hassan B, Akcakanat A, Sangai T, Evans KW, Adkins F, Eterovic AK, Zhao H, Chen K, Chen H, Do K-A. Catalytic mTOR inhibitors can overcome intrinsic and acquired resistance to allosteric mTOR inhibitors. Oncotarget. 2014;5:8544.
Zhai B, Hu F, Jiang X, Xu J, Zhao D, Liu B, Pan S, Dong X, Tan G, Wei Z. Inhibition of Akt reverses the acquired resistance to sorafenib by switching protective autophagy to autophagic cell death in hepatocellular carcinoma. Mol Cancer Ther. 2014;13:1589–98.
Dupere-Richer D, Kinal M, Menasche V, Nielsen TH, Del Rincon S, Pettersson F, Miller WH. Vorinostat-induced autophagy switches from a death-promoting to a cytoprotective signal to drive acquired resistance. Cell Death Dis. 2013;4:e486.
Meng H, Mai WX, Zhang H, Xue M, Xia T, Lin S, Wang X, Zhao Y, Ji Z, Zink JI. Codelivery of an optimal drug/siRNA combination using mesoporous silica nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo. ACS Nano. 2013;7:994–1005.
Hu C-MJ, Zhang L. Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem Pharmacol. 2012;83:1104–11.
Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011;63:170–83.
Stylianopoulos T. EPR-effect: utilizing size-dependent nanoparticle delivery to solid tumors. Ther Deliv. 2013;4:421–3.
Gopal NO, Lo HH, Ke TF, Lee CH, Chou CC, Wu JD, Sheu SC, Ke SC. Visible light active phosphorus-doped TiO2 nanoparticles: an EPR evidence for the enhanced charge separation. J Phys Chem C. 2012;116:16191–7.
Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185–98.
Cheng R, Meng F, Deng C, Klok HA, Zhong Z. Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials. 2013;34:3647–57.
Zhao J, Mi Y, Liu Y, Feng SS. Quantitative control of targeting effect of anticancer drugs formulated by ligand-conjugated nanoparticles of biodegradable copolymer blend. Biomaterials. 2012;33:1948–58.
Tabatabaei SN, Girouard H, Carret AS, Martel S. Remote control of the permeability of the blood–brain barrier by magnetic heating of nanoparticles: a proof of concept for brain drug delivery. J Control Release. 2015;206:49–57.
Zhou J, Patel TR, Fu M, Bertram JP, Saltzman WM. Octa-functional PLGA nanoparticles for targeted and efficient siRNA delivery to tumors. Biomaterials. 2012;33:583–91.
Kirtane AR, Panyam J. Polymer nanoparticles: weighing up gene delivery. Nat Nanotechnol. 2013;8:805–6.
Pan L, He Q, Liu J, Chen Y, Ma M, Zhang L, Shi J. Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles. J Am Chem Soc. 2012;134:5722–5.
Parveen S, Misra R, Sahoo SK. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine. 2012;8:147–66.
Zhao L, Su R, Cui W, Shi Y, Liu L, Su C. Preparation of biocompatible heat-labile enterotoxin subunit B-bovine serum albumin nanoparticles for improving tumor-targeted drug delivery via heat-labile enterotoxin subunit B mediation. Int J Nanomedicine. 2014;9:2149.
Zhao L, Li H, Shi Y, Wang G, Liu L, Su C, Su R. Nanoparticles inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery via cell surface-related GRP78. Int J Nanomedicine. 2015;10:245.