Chitosan nanoparticle-mediated co-delivery of shAtg-5 and gefitinib synergistically promoted the efficacy of chemotherapeutics through the modulation of autophagy
Tóm tắt
Autophagy reportedly plays vital and complex roles in many diseases. During times of starvation or energy deficiency, autophagy will occur at higher levels to provide cells with the nutrients or energy necessary to survive in stressful conditions. Some anti-cancer drugs induce protective autophagy and reduce cell apoptosis. Autophagy can adversely affect apoptosis, and blocking autophagy will increase the sensitivity of cells to apoptosis signals. We designed chitosan nanoparticles (NPs) to promote the co-delivery of gefitinib (an anti-cancer drug) and shRNA-expressing plasmid DNA that targets the Atg-5 gene (shAtg-5) as an autophagy inhibitor to improve anti-cancer effects and autophagy mediation. The results showed that when compared to treatment with a single drug, chitosan NPs were able to facilitate the intracellular distribution of NPs, and they improved the transfection efficiency of gene in vitro. The co-delivery of gefitinib and shAtg-5 increased cytotoxicity, induced significant apoptosis through the prohibition of autophagy, and markedly inhibited tumor growth in vivo. The co-delivery of gefitinib/shAtg-5 in chitosan NPs produced superior anti-cancer efficacy via the internalization effect of NPs, while blocking autophagy with shAtg-5 enhanced the synergistic antitumor efficacy of gefitinib.
Tài liệu tham khảo
Sotiropoulou PA, Christodoulou MS, Silvani A, et al. Chemical approaches to targeting drug resistance in cancer stem cells. Drug Discov Today. 2014;19(10):1547–62.
Kathawala RJ, Gupta P, Ashby CR Jr, Chen ZS. The modulation of ABC transporter-mediated multidrug resistance in cancer: a review of the past decade. Drug Resist Updat. 2015;18:1–17.
Kibria G, Hatakeyama H, Harashima H. Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system. Arch Pharm Res. 2014;37(1):4–15.
Chen N, Debnath J. Autophagy and tumorigenesis. FEBS Lett. 2010;584(7):1427–35.
Rao S, Yang H, Penninger JM, Kroemer G. Autophagy in non-small cell lung carcinogenesis: a positive regulator of antitumor immunosurveillance. Autophagy. 2014;10(3):529–31.
Mukhtar E, Adhami VM, Khan N, Mukhtar H. Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents. Curr Drug Targets. 2012;13(14):1831–41.
Chaabane W, User SD, El-Gazzah M, et al. Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp. 2013;61(1):43–58.
Xie Y, Murray-Stewart T, Wang Y, et al. Self-immolative nanoparticles for simultaneous delivery of microRNA and targeting of polyamine metabolism in combination cancer therapy. J Control Release. 2017;246:110–9.
Conde J, Oliva N, Zhang Y, Artzi N. Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model. Nat Mater. 2016;15:1128–38.
Duan S, Yang Y, Zhang C, Zhao N, Xu FJ. NIR-responsive polycationic gatekeeper-cloaked hetero-nanoparticles for multimodal imaging-guided triple-combination therapy of cancer. Small. 2016. doi:10.1002/smll.201603133 (Epub ahead of print).
Elgogary A, Xu Q, Poore B, Alt J, et al. Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer. Proc Natl Acad Sci USA. 2016;113:E5328–36.
Gilam A, Conde J, Weissglas-Volkov D, Oliva N, Friedman E, Artzi N, Shomron N. Local microRNA delivery targets Palladin and prevents metastatic breast cancer. Nat Commun. 2016;7:12868.
Kong F, Zhang H, Qu X, et al. Gold nanorods, DNA origami, and porous silicon nanoparticle-functionalized biocompatible double emulsion for versatile targeted therapeutics and antibody combination therapy. Adv Mater. 2016;28:10195–203.
Conde J, Bao C, Tan Y, et al. Dual targeted immunotherapy via in vivo delivery of biohybrid RNAi-peptide nanoparticles to tumour-associated macrophages and cancer cells. Adv Funct Mater. 2015;25:4183–94.
Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65(1):71–9.
Panzarini E, Dini L. Nanomaterial-induced autophagy: a new reversal MDR tool in cancer therapy? Mol Pharm. 2014;11(8):2527–38.
Bazak R, Houri M, El Achy S, et al. Cancer active targeting by nanoparticles: a comprehensive review of literature. J Cancer Res Clin Oncol. 2015;141(5):769–84.
Gao Z, Zhang L, Sun Y. Nanotechnology applied to overcome tumor drug resistance. J Control Release. 2012;162(1):45–55.
Liu Y, Wang Y, Zhang C, et al. Core–shell nanoparticles based on pullulan and poly(β-amino) ester for hepatoma-targeted codelivery of gene and chemotherapy agent. ACS Appl Mater Interfaces. 2014;6(21):18712–20.
Guan X, Li Y, Jiao Z, et al. Codelivery of antitumor drug and gene by a pH-sensitive charge-conversion system. ACS Appl Mater Interfaces. 2015;7(5):3207–15.
Tsouris V, Joo MK, Kim SH, et al. Nano carriers that enable co-delivery of chemotherapy and RNAi agents for treatment of drug-resistant cancers. Biotechnol Adv. 2014;32(5):1037–50.
Dong D, Gao W, Liu Y, Qi XR. Therapeutic potential of targeted multifunctional nanocomplex co-delivery of siRNA and low-dose doxorubicin in breast cancer. Cancer Lett. 2015;359(2):178–86.
Song H, Su C, Cui W, et al. Folic acid-chitosan conjugated nanoparticles for improving tumor-targeted drug delivery. Biomed Res Int. 2013:723158.
DeBiasio R, Bright GR, Ernst LA, Waggoner AS, Taylor DL. Five-parameter fluorescence imaging: wound healing of living Swiss 3T3 cells. J Cell Biol. 1987;105(4):1613–22.
Brauns SC, Milne P, Naudé R, Van de Venter M. Selected cyclic dipeptides inhibit cancer cell growth and induce apoptosis in HT-29 colon cancer cells. Anticancer Res. 2004;24(3a):1713–9.
Su C, Li H, Shi Y, et al. Carboxymethyl-β-cyclodextrin conjugated nanoparticles facilitate therapy for folate receptor-positive tumor with the mediation of folic acid. Int J Pharm. 2014;474(1–2):202–11.
Zhao L, Su R, Cui W, et al. 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;9:2149–56.
Shukla SK, Mishra AK, Arotiba OA, Mamba BB. Chitosan-based nanomaterials: a state-of-the-art review. Int J Biol Macromol. 2013;59:46–58.
Yang Y, Wang S, Wang Y, et al. Advances in self-assembled chitosan nanomaterials for drug delivery. Biotechnol Adv. 2014;32(7):1301–16.
Garcia-Fuentes M, Alonso MJ. Chitosan-based drug nanocarriers: where do we stand? J Control Release. 2012;161(2):496–504.
Paiva D, Ivanova G, Pereira Mdo C, Rocha S. Chitosan conjugates for DNA delivery. Phys Chem Chem Phys. 2013;15(28):11893–9.
Yhee JY, Song S, Lee SJ, et al. Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance. J Control Release. 2015;198:1–9.
Eisenberg-Lerner A, Bialik S, Simon HU, Kimchi A. Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 2009;16(7):966–75.