Dual drug-loaded PLA nanoparticles bypassing drug resistance for improved leukemia therapy
Source abstract
Abstract
Drug resistance is still a bottle-neck hindering successful chemotherapy in leukemia treatment. Nanocarriers have emerged as promising candidates to circumvent drug resistance and discover potent drug combinations. Here, we showed that co-encapsulation of daunorubicin (DNR) and glycyrrhizic acid (GA) in polylactic acid (PLA) nanoparticles effectively bypassed drug resistance and remarkably inhibited the growth of drug-resistant leukemia cells. The quantification of intracellular drug found that the encapsulation effectively increased drug uptake in the resistant K562/A02 cells. Modification of P-glycoprotein antibody on nanoparticles further enhanced drug accumulation in the leukemia cells, which was also confirmed by fluorescent microscopy imaging. More importantly, loaded in PLA nanoparticles, DNR and GA exerted an excellent synergistic effect, leading to significantly improved cell inhibition compared to the treatments without nanocarriers and those with a single drug. Correlative mechanism study revealed that the drug delivery system drastically enhanced cell apoptosis by regulating apoptotic genes but did not influence MDR1 expression. The present study proposes a versatile strategy to improve the therapeutic efficacy against drug-resistant leukemia and inspires the discovery of more potent drug combinations for enhanced leukemia therapy.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Pharmacological Effects of Natural Compounds · Retinoids in leukemia and cellular processes · Acute Myeloid Leukemia Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (34)
Show source-provided references
1. Bishop JF (1997) The treatment of adult acute myeloid leukemia. Semin Oncol 24:57–69
2. Cai Y, Xu Y, Chan HF, Fang X, He C, Chen M (2016) Glycyrrhetinic acid mediated drug delivery carriers for hepatocellular carcinoma therapy. Mol Pharm 13:699–70910.1021/acs.molpharmaceut.5b00677 ↗
3. Chen FY, Zhang Y, Chen XY, Li JQ, Xiao XP, Yu LL, Tang Q (2017) Development of a hybrid paclitaxel-loaded arsenite nanoparticle (HPAN) delivery system for synergistic combined therapy of paclitaxel-resistant cancer. J Nanopart Res 19:15510.1007/s11051-017-3848-0 ↗
4. Csuk R (2014) Recent developments in the synthesis of antitumor-active glycyrrhetinic acid derivatives. Mini-Rev Org Chem 11:253–26110.2174/1570193X1103140915105049 ↗
5. Cui F, Li Y, Zhou S, Jia M, Yang X, Yu F, Ye S, Hou Z, Xie L (2013) A comparative in vitro evaluation of self-assembled PTX-PLA and PTX-MPEG-PLA nanoparticles. Nanoscale Res Lett 8:30110.1186/1556-276X-8-301 ↗
6. Danafar H, Rostamizadeh K, Davaran S, Hamidi M (2014) PLA-PEG-PLA copolymer-based polymersomes as nanocarriers for delivery of hydrophilic and hydrophobic drugs: preparation and evaluation with atorvastatin and lisinopril. Drug Dev Ind Pharm 40:1411–142010.3109/03639045.2013.828223 ↗
7. Döhner H, Weisdorf DJ, Bloomfield CD (2015) Acute myeloid leukemi. N Engl J Med 373:1136–115210.1056/NEJMra1406184 ↗
8. Fox LC, Cummins KD, Costello B, Yeung D, Cleary R, Forsyth C, Tatarczuch M, Burbury K, Motorna O, Shortt J, Fleming S, McQuillan A, Schwarer A, Harrup R, Holmes A, Ratnasingam S, Chan KL, Hsu WH, Ashraf A, Putt F, Grigg A (2017) The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia. Blood Adv 1:802–81110.1182/bloodadvances.2016003889 ↗
9. Halley PD, Lucas CR, McWilliams EM, Webber MJ, Patton RA, Kural C, Lucas DM, Byrd JC, Castro CE (2016) Daunorubicin-loaded DNA origami nanostructures circumvent drug-resistance mechanisms in a leukemia model. Small 12:308–32010.1002/smll.201502118 ↗
10. He SQ, Gao M, Fu YF et al (2015) Glycyrrhizic acid inhibits leukemia cell growth and migration via blocking AKT/mTOR/STAT3 signaling. Int J Clin Exp Med 8:5175
11. Hibasami H, Iwase H, Yoshioka K, Takahashi H (2005) Glycyrrhizin induces apoptosis in human stomach cancer KATO III and human promyelotic leukemia HL-60 cells. Int J Mol Med 16:233–236
12. Holohan C, Van Schaeybroeck S, Longley DB et al (2013) Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 13:714–72610.1038/nrc3599 ↗
13. Kihara R, Nagata Y, Kiyoi H, Kato T, Yamamoto E, Suzuki K, Chen F, Asou N, Ohtake S, Miyawaki S, Miyazaki Y, Sakura T, Ozawa Y, Usui N, Kanamori H, Kiguchi T, Imai K, Uike N, Kimura F, Kitamura K, Nakaseko C, Onizuka M, Takeshita A, Ishida F, Suzushima H, Kato Y, Miwa H, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Naoe T (2014) Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia 28:1586–159510.1038/leu.2014.55 ↗
14. Kirtane AR, Kalscheuer SM, Panyam J (2013) Exploiting nanotechnology to overcome tumor drug resistance: challenges and opportunities. Adv Drug Deliv Rev 65:1731–174710.1016/j.addr.2013.09.001 ↗
15. Li R, Wu R, Zhao L et al (2010) P-glycoprotein antibody functionalized carbon nanotube overcomes the multidrug resistance of human leukemia cells. ACS Nano 4:1399–140810.1021/nn9011225 ↗
16. Li L, Osdal T, Ho Y, Chun S, McDonald T, Agarwal P, Lin A, Chu S, Qi J, Li L, Hsieh YT, Dos Santos C, Yuan H, Ha TQ, Popa M, Hovland R, Bruserud Ø, Gjertsen BT, Kuo YH, Chen W, Lain S, McCormack E, Bhatia R (2014) SIRT1 activation by a c-MYC oncogenic network promotes the maintenance and drug resistance of human FLT3-ITD acute myeloid leukemia stem cells. Cell Stem Cell 15:431–44610.1016/j.stem.2014.08.001 ↗
17. Loos C, Syrovets T, Musyanovych A, Mailänder V, Landfester K, Simmet T (2014) Amino-functionalized nanoparticles as inhibitors of mTOR and inducers of cell cycle arrest in leukemia cells. Biomaterials 35:1944–195310.1016/j.biomaterials.2013.11.056 ↗
18. Meng H, Mai WX, Zhang H, Xue M, Xia T, Lin S, Wang X, Zhao Y, Ji Z, Zink JI, Nel AE (2013) 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 7:994–100510.1021/nn3044066 ↗
19. Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12:991–100310.1038/nmat3776 ↗
20. Nishida Y, Maeda A, Chachad D, Ishizawa J, Qiu YH, Kornblau SM, Kimura S, Andreeff M, Kojima K (2015) Preclinical activity of the novel B-cell-specific Moloney murine leukemia virus integration site 1 inhibitor PTC-209 in acute myeloid leukemia: implications for leukemia therapy. Cancer Sci 106:1705–171310.1111/cas.12833 ↗
21. Picaud S, Fedorov O, Thanasopoulou A, Leonards K, Jones K, Meier J, Olzscha H, Monteiro O, Martin S, Philpott M, Tumber A, Filippakopoulos P, Yapp C, Wells C, Che KH, Bannister A, Robson S, Kumar U, Parr N, Lee K, Lugo D, Jeffrey P, Taylor S, Vecellio ML, Bountra C, Brennan PE, O’Mahony A, Velichko S, Muller S, Hay D, Daniels DL, Urh M, la Thangue NB, Kouzarides T, Prinjha R, Schwaller J, Knapp S (2015) Generation of a selective small molecule inhibitor of the CBP/p300 bromodomain for leukemia therapy. Cancer Res 75:5106–511910.1158/0008-5472.CAN-15-0236 ↗
22. Rochani AK, Girija AR, Borah A et al (2016) Heat-shock protein 90–targeted nano anticancer therapy. J Pharm Sci 105:1454–146610.1016/j.xphs.2015.10.007 ↗
23. Sheng X, Tucci J, Mittelman SD (2015) Reduction of oxidative stress promotes daunorubicin resistance in acute lymphoblastic leukemia cells. Cancer Res 75(15 Supplement):124710.1158/1538-7445.AM2015-1247 ↗
24. Singh MR, Bart G, Zinke-Allmang M (2010) Polaron hopping in nano-scale poly (dA)–poly (dT) DNA. Nanoscale Res Lett 5:501–50410.1007/s11671-010-9548-7 ↗
25. Stauss HJ, Morris EC (2013) Immunotherapy with gene-modified T cells: limiting side effects provides new challenges. Gene Ther 20:1029–103210.1038/gt.2013.34 ↗
26. Thirugnanam S, Xu L, Ramaswamy K, Gnanasekar M (2008) Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. Oncol Rep 20:1387–1392
27. Wang C, Xu H, Liang C, Liu Y, Li Z, Yang G, Cheng L, Li Y, Liu Z (2013) Iron oxide@ polypyrrole nanoparticles as a multifunctional drug carrier for remotely controlled cancer therapy with synergistic antitumor effect. ACS Nano 7:6782–679510.1021/nn4017179 ↗
28. Whitlock JA, Greer JP, Lukens JN (1991) Epipodophyllotoxin-related leukemia. Cancer 68:1–60410.1002/1097-0142(19910801)68:3<600::AID-CNCR2820680326>3.0.CO;2-F ↗
29. Zhang XY, Hu WB, Li J et al (2012) A comparative study of cellular uptake and cytotoxicity of multi-walled carbon nanotubes, graphene oxide, and nanodiamond. Toxicol Res 1:62–6810.1039/c2tx20006f ↗
30. Zhang W, Gao C, Konopleva M, Chen Y, Jacamo RO, Borthakur G, Cortes JE, Ravandi F, Ramachandran A, Andreeff M (2014) Reversal of acquired drug resistance in FLT3-mutated acute myeloid leukemia cells via distinct drug combination strategies. Clin Cancer Res 20:2363–237410.1158/1078-0432.CCR-13-2052 ↗
31. Zhang Y, Chen H, Zhou S, Wang SX, Zheng K, Xu DD, Liu YT, Wang XY, Wang X, Yan HZ, Zhang L, Liu QY, Chen WQ, Wang YF (2015a) Sp1 and c-Myc modulate drug resistance of leukemia stem cells by regulating survivin expression through the ERK-MSK MAPK signaling pathway. Mol Cancer 14:5610.1186/s12943-015-0326-0 ↗
32. Zhang XY, Wang K, Liu MY et al (2015b) Polymeric AIE-based nanoprobes for biomedical applications: recent advances and perspectives. Nanoscale 7:11486–1150810.1039/C5NR01444A ↗
33. Zhao MX, Zhu BJ (2016) The research and applications of quantum dots as nano-carriers for targeted drug delivery and cancer therapy. Nanoscale Res Lett 11:20710.1186/s11671-016-1394-9 ↗
34. Zhu H, Chen H, Zeng X, Wang Z, Zhang X, Wu Y, Gao Y, Zhang J, Liu K, Liu R, Cai L, Mei L, Feng SS (2014) Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance. Biomaterials 35:2391–240010.1016/j.biomaterials.2013.11.086 ↗