Magnetic and temperature-sensitive solid lipid particles (mag. SLPs) were prepared in the presence of oleic acid-coated iron oxide (IO-OA) nanoparticles with 1-tetradecanol and poly(ethylene oxide)-block-poly(ε-caprolactone) as lipid and stabilizing surfactant-like agents, respectively. The particles, typically ~850 nm in hydrodynamic size, showed heat dissipation under the applied alternating magnetic field. Cytotoxic activity of the mag.SLPs, non-magnetic SLPs, and iron oxide nanoparticles was compared concerning the mammalian cancer cell lines and their drug-resistant counterparts using trypan blue exclusion test and MTT assay. The mag.SLPs exhibited dose-dependent cytotoxicity against human leukemia cell lines growing in suspension (Jurkat and HL-60/wt), as well as the doxorubicin (Dox)- and vincristine-resistant HL-60 sublines. The mag.SLPs showed higher cytotoxicity toward drug-resistant sublines as compared to Dox. The human glioblastoma cell line U251 growing in a monolayer culture was also sensitive to mag.SLPs cytotoxicity. Staining of U251 cells with the fluorescent dyes Hoechst 33342 and propidium iodide (PI) revealed that mag.SLPs treatment resulted in an increased number of cells with condensed chromatin and/or fragmented nuclei as well as with blebbing of the plasma membranes. While the Hoechst 33342 staining of cell suggested the pro-apoptotic activity of the particles, the PI staining indicated the pro-necrotic changes in the target cells. These conclusions were confirmed by Western blot analysis of apoptosis-related proteins, study of DNA fragmentation (DNA laddering due to the inter-nucleosomal cleavage and DNA comets due to single strand breaks), as well as by FACS analysis of the patterns of cell cycle distribution (pre-G1 phase) and Annexin V/PI staining of the treated Jurkat cells. The induction of apoptosis or necrosis by the particles used to treat Jurkat cells depended on the dose of the particles. Production of the reactive oxygen species (ROS) was proposed as a potential mechanism of mag.SLPs-induced cytotoxicity. Accordingly, hydrogen peroxide and superoxide radical levels in mag.SLPs-treated Jurkat leukemic cells were increased by ~20-40 and ~70%, respectively. In contrast, the non-magnetic SLPs and neat iron oxides did not influence ROS levels significantly. Thus, the developed mag.SLPs can be used for effective killing of human tumor cells, including drug-resistant ones.

Department of Medicine 1 Medical University of Vienna Institute of Cancer Research and Comprehensive Cancer Center Vienna Austria

Department of Regulation of Cell Proliferation and Apoptosis Institute of Cell Biology National Academy of Science of Ukraine Lviv Ukraine

Institute of Experimental Physics Slovak Academy of Sciences Košice Slovakia

Institute of Macromolecular Chemistry of the Czech Academy of Sciences Prague Czechia

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Abakumov M. A., Semkina A. S., Skorikov A. S., Vishnevskiy D. A., Ivanova A. V., Mironova E., et al. . (2018). Toxicity of iron oxide nanoparticles: Size and coating effects. J. Biochem. Mol. Toxicol. 32:e22225. 10.1002/jbt.22225 PubMed DOI

Akbarzadeh A., Rezaei-Sadabady S., Davaran S., Joo S. W., Zarghami N., Hanifehpour Y., et al. . (2013). Liposome: classification, preparation, and applications. Nanoscale Res. Lett. 8:102. 10.1186/1556-276X-8-102 PubMed DOI PMC

Albuquerque J., Moura C., Sarmento B., Reis S. (2015). Solid lipid nanoparticles: a potential multifunctional approach towards rheumatoid arthritis theranostics. Molecules 20, 11103–11118. 10.3390/molecules200611103 PubMed DOI PMC

Atale N., Gupta S., Yadav U. C., Rani V. (2014). Cell-death assessment by fluorescent and nonfluorescent cytosolic and nuclear staining techniques. J. Microsc. 255, 7–19. 10.1111/jmi.12133 PubMed DOI

Bae Y. H., Park K. (2011). Targeted drug delivery to tumors: myths, reality and possibility. J. Control. Release 153, 198–205. 10.1016/j.jconrel.2011.06.001 PubMed DOI PMC

Bahrami B., Hojjat-Farsangi M., Mohammadi H., Anvari E., Ghalamfarsa G., Yousefi M., et al. . (2017). Nanoparticles and targeted drug delivery in cancer therapy. Immunol. Lett. 190, 64–83. 10.1016/j.imlet.2017.07.015 PubMed DOI

Bayda S., Hadla M., Palazzolo S., Riello P., Corona G., Toffoli G., et al. . (2018). Inorganic nanoparticles for cancer therapy: a transition from lab to clinic. Curr. Med. Chem. 25, 4269–4303. 10.2174/0929867325666171229141156 PubMed DOI

Berkowitz A. E., Schuele W. J., Flanders P. J. (1968). Influence of crystallite size on the magnetic properties of acicular γ-Fe2O3 particles. J. Appl. Phys. 39, 1261–1263. 10.1063/1.1656256 DOI

Berry C. C., Charles S., Wells S., Dalby M. J., Curtis A. S. (2004). The influence of transferrin stabilised magnetic nanoparticles on human dermal fibroblasts in culture. Int. J. Pharm. 269, 211–225. 10.1016/j.ijpharm.2003.09.042 PubMed DOI

Boraschi D., Costantino L., Italiani P. (2012). Interaction of nanoparticles with immunocompetent cells: nanosafety considerations. Nanomedicine 7, 121–131. 10.2217/nnm.11.169 PubMed DOI

Brezaniova I., Hruby M., Kralova J., Kral V., Cernochova Z., Cernoch P., et al. . (2016). Temoporfin-loaded 1-tetradecanol-based thermoresponsive solid lipid nanoparticles for photodynamic therapy. J. Control. Release 241, 34–44. 10.1016/j.jconrel.2016.09.009 PubMed DOI

Brustmann H. (2007). Poly(ADP-ribose) polymerase (PARP) and DNA-fragmentation factor (DFF45): expression and correlation in normal, hyperplastic and neoplastic endometrial tissues. Pathol. Res. Pract. 203, 65–72. 10.1016/j.prp.2006.12.003 PubMed DOI

Cancer Research UK (2019). https://www.cancerresearchuk.org/health-professional/cancer-statistics/worldwide-cancer (accessed July 26, 2019).

Di Bona K. R., Xu Y., Ramirez P. A., De Laine J., Parker C., Bao Y., et al. . (2014). Surface charge and dosage dependent potential developmental toxicity and biodistribution of iron oxide nanoparticles in pregnant CD-1 mice. Reprod. Toxicol. 50, 36–42. 10.1016/j.reprotox.2014.09.010 PubMed DOI

Eguchi H., Umemura M., Kurotani R., Fukumura H., Sato I., Kim J. H., et al. . (2015). A magnetic anti-cancer compound for magnet-guided delivery and magnetic resonance imaging. Sci. Rep. 5:9194. 10.1038/srep09194 PubMed DOI PMC

Estelrich J., Sánchez-Martín M. J., Busquets M. A. (2015). Nanoparticles in magnetic resonance imaging: From simple to dual contrast agents. Int. J. Nanomed. 10, 1727–1741. 10.2147/IJN.S76501 PubMed DOI PMC

Fang M., Ström V., Olsson R. T., Belova L., Rao K. V. (2012). Particle size and magnetic properties dependence on growth temperature for rapid mixed co-precipitated magnetite nanoparticles. Nanotechnology 23:145601. 10.1088/0957-4484/23/14/145601 PubMed DOI

Finiuk N., Boiko N., Klyuchivska O., Kobylinska L., Kril I., Zimenkovsky B., et al. . (2017). 4-Thiazolidinone derivative Les-3833 effectively inhibits viability of human melanoma cells through activating apoptotic mechanisms. Croat. Med. J. 58,129–139. 10.3325/cmj.2017.58.129 PubMed DOI PMC

Gorini S., De Angelis A., Berrino L., Malara N., Rosano G., Ferraro E. (2018). Chemotherapeutic drugs and mitochondrial dysfunction: focus on doxorubicin, trastuzumab, and sunitinib. Oxid. Med. Cell Longev. 2018:7582730. 10.1155/2018/7582730 PubMed DOI PMC

Herceg Z., Wang Z. Q. (1999). Failure of poly(ADP-ribose) polymerase cleavage by caspases leads to induction of necrosis and enhanced apoptosis. Mol. Cell Biol. 19, 5124–5133. 10.1128/mcb.19.7.5124 PubMed DOI PMC

Housman G., Byler S., Heerboth S., Lapinska K., Longacre M., Snyder N., et al. . (2014). Drug resistance in caner: an overview. Cancers 6, 1769–1792. 10.3390/cancers6031769 PubMed DOI PMC

Hsiao J. K., Chu H. H., Wang Y. H., Lai C. W., Chou P. T., Hsieh S. T., et al. . (2008). Macrophage physiological function after superparamagnetic iron oxide labeling. NMR Biomed. 21, 820–829. 10.1002/nbm.1260 PubMed DOI

Huang X., Brazel C. S. (2001). On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J. Control. Release 73, 121–136. 10.1016/s0168-3659(01)00248-6 PubMed DOI

Kafrouni L., Savadogo O. (2016). Recent progress on magnetic nanoparticles for magnetic hyperthermia. Prog. Biomater. 5, 147–160. 10.1007/s40204-016-0054-6 PubMed DOI PMC

Kaur P., Aliru M. L., Chadha A. S., Asea A., Krishnan S. (2016). Hyperthermia using nanoparticles - Promises and pitfalls. Int. J. Hyperthermia 32, 76–88. 10.3109/02656736.2015.1120889 PubMed DOI PMC

Ke H., Wang Y., Ren D., Wang L. (2008). Adriamycin sensitizes adriamycin-resistant HL-60/ADR cells to TRAIL-mediated apoptosis. Chin. J. Clin. Oncol. 5, 354–360. 10.1007/s11805-008-0354-2 DOI

Kim H., Beack S., Han S., Shin M., Lee T., Park Y., et al. . (2018). Multifunctional photonic nanomaterials for diagnostic, therapeutic, and theranostic applications. Adv. Mater. 30:1701460. 10.1002/adma.201701460 PubMed DOI

Kostiv U., Patsula V., Noculak A., Podhorodecki A., Větvička D., Poučková P., et al. . (2017). Phthalocyanine-conjugated upconversion NaYF4:Yb3+/Er3+@SiO2 nanospheres for NIR-triggered photodynamic therapy in a tumor mouse model. ChemMedChem 12, 2066–2073. 10.1002/cmdc.201700508 PubMed DOI

Leist M., Single B., Kunstle G., Volbracht C., Hentze H., Nicotera P. (1997). Apoptosis in the absence of poly-(ADP-ribose) polymerase. Biochem. Biophys. Res. Commun. 233, 518–522. 10.1006/bbrc.1997.6491 PubMed DOI

Li L., Tong R., Li M., Kohane D. S. (2016). Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy. Acta Biomater. 33, 34–39. 10.1016/j.actbio.2016.01.039 PubMed DOI PMC

Li Q., Kartikowati C. W., Horie S., Ogi T., Iwaki T., Okuyama K. (2017). Correlation between particle size/domain structure and magnetic properties of highly crystalline Fe3O4 nanoparticles. Sci. Rep. 7:9894. 10.1038/s41598-017-09897-5 PubMed DOI PMC

Li Z. H., Zhang J., Liu X. Q., Geng P. F., Ma J. L., Wang B., et al. . (2017). Identification of thiazolo[5,4-d]pyrimidine derivatives as potent antiproliferative agents through the drug repurposing strategy. Eur. J. Med. Chem. 135, 204–212. 10.1016/j.ejmech.2017.04.056 PubMed DOI

Liao W., McNutt M. A., Zhu W. G. (2009). The comet assay: a sensitive method for detecting DNA damage in individual cells. Methods 48, 46–53. 10.1016/j.ymeth.2009.02.016 PubMed DOI

Liong M., Lu J., Kovochich M., Xia T., Ruehm S. G., Nel A. E., et al. . (2008). Multifuncional inorganic nanoparticles for imaging, targeting, and drug delivery. ACS Nano 2, 889–896. 10.1021/nn800072t PubMed DOI PMC

Lippens R. J., Rotteveel J. J., Otten B. J., Merx H. (1998). Chemotherapy with Adriamycin (doxorubicin) and CCNU (lomustine) in four children with recurrent craniopharyngioma. Eur. J. Paediatr. Neurol. 2, 263–268. 10.1016/s1090-3798(98)80040-8 PubMed DOI

Liu K., Qin Y.-H., Yu J.-Y., Ma H., Song X.-L. (2016). 3-β-Erythrodiol isolated from Conyza canadensis inhibits MKN-45 human gastric cancer cell proliferation by inducing apoptosis, cell cycle arrest, DNA fragmentation, ROS generation and reduces tumor weight and volume in mouse xenograft model. Oncol. Rep. 35, 328–2338. 10.3892/or.2016.4610 PubMed DOI

Mahmoudi M., Laurent S., Shokrgozar M. A., Hosseinkhani M. (2011). Toxicity evaluations of superparamagnetic iron oxide nanoparticles: Cell “vision” versus physicochemical properties of nanoparticles. ACS Nano 5, 7263–7276. 10.1021/nn2021088 PubMed DOI

Mascolo M. C., Pei Y., Ring T. A. (2013). Room temperature co-precipitation synthesis of magnetite nanoparticles in a large pH window with different base. Materials 6, 5549–5567. 10.3390/ma6125549 PubMed DOI PMC

Minotti G., Menna P., Salvatorelli E., Cairo G., Gianni L. (2004). Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 56, 185–229. 10.1124/pr.56.2.6 PubMed DOI

Mishra V., Bansal K. K., Verma A., Yadav N., Thakur S., Sudhakar K., et al. . (2018). Solid lipid nanoparticles: emerging colloidal nano drug delivery systems. Pharmaceutics 10:191. 10.3390/pharmaceutics10040191 PubMed DOI PMC

Mody V. V., Cox A., Shah S., Singh A., Bevins W., Parihar H. (2014). Magnetic nanoparticle drug delivery systems for targeting tumor, Appl. Nanosci. 4, 385–392. 10.1007/s13204-013-0216-y DOI

Muñoz de Escalona M., Sáez-Fernández E., Prados J. C., Melguizo C., Arias J. L. (2016). Magnetic solid lipid nanoparticles in hyperthermia against colon cancer. Int. J. Pharm. 504, 11–19. 10.1016/j.ijpharm.2016.03.005 PubMed DOI

Myung J. H., Hsu H. J., Bugno J., Tam K. A., Hong S. (2017). Chemical structure and surface modification of dendritic nanomaterials tailored for therapeutic and diagnostic applications. Curr. Top. Med. Chem. 17, 1542–1554. 10.2174/1568026616666161222104112 PubMed DOI

Naveau A., Smirnov P., Ménager C., Gazeau F., Clément O., Lafont A., et al. . (2006). Phenotypic study of human gingival fibroblasts labeled with superparamagnetic anionic nanoparticles. J. Periodontol. 77, 238–247. 10.1902/jop.2006.050064 PubMed DOI

Nedelkoski Z., Kepaptsoglou D., Lari L., Wen T., Booth R. A., Oberdick S. D., et al. . (2017). Origin of reduced magnetization and domain formation in small magnetite nanoparticles. Sci. Rep. 7:45997. 10.1038/srep45997 PubMed DOI PMC

Palazzolo S., Bayda S., Hadla M., Caligiuri I., Corona G., Toffoli G., et al. . (2018). The clinical translation of organic nanomaterials for cancer therapy: a focus on polymeric nanoparticles, micelles, liposomes and exosomes. Curr. Med. Chem. 25, 4224–4268. 10.2174/0929867324666170830113755 PubMed DOI

Palumbo M. O., Kavan P., Miller W. H., Panasci L., Assouline S., Johnson N., et al. . (2013). Systemic cancer therapy: achievements and challenges that lie ahead. Front. Pharmacol. 4:57. 10.3389/fphar.2013.00057 PubMed DOI PMC

Panchuk R. R., Lehka L. V., Terenzi A., Matselyukh B. P., Rohr J., Jha A. K., et al. . (2017). Rapid generation of hydrogen peroxide contributes to the complex cell death induction by the angucycline antibiotic landomycin E. Free Radical Bio. Med. 106, 134–147. 10.1016/j.freeradbiomed.2017.02.024 PubMed DOI PMC

Périgo E. A., Hemery G., Sandre O., Ortega D., Garaio E., Plazaola F., et al. (2015). Fundamentals and advances in magnetic hyperthermia. Appl. Phys. Rev. 2:041302 10.1063/1.4935688 DOI

Périgo E. A., Sampaio F. A., de Campos M. F. (2013). On the specific absorption rate of hyperthermia fluids. Appl. Phys. Lett. 103:264107 10.1063/1.4860966 DOI

Phaniendra A., Jestadi D. B., Periyasamy L. (2015). Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem. 30, 11–26. 10.1007/s12291-014-0446-0 PubMed DOI PMC

Plouffe B. D., Murthy S. K., Lewis L. H. (2015). Fundamentals and application of magnetic particles in cell isolation and enrichment: a review. Rep. Prog. Phys. 78:016601. 10.1088/0034-4885/78/1/016601 PubMed DOI PMC

Radu M., Munteanu M. C., Petrache S., Serban A. I., Dinu D., Hermenean A., et al. . (2010). Depletion of intracellular glutathione and increased lipid peroxidation mediate cytotoxicity of hematite nanoparticles in MRC-5 cells. Acta Biochim. Pol. 57, 355–360. 10.18388/abp.2010_2416 PubMed DOI

Salazar J. S., Perez L., de Abril O., Phuoc L. T., Ihiawakrim D., Vazquez M., et al. (2011). Magnetic iron oxide nanoparticles in 10–40 nm range: composition in terms of magnetite/maghemite ratio and effect on the magnetic properties. Chem. Mater. 23, 1379–1386. 10.1021/cm103188a DOI

Senkiv J., Finiuk N., Kaminskyy D., Havrylyuk D., Wojtyra M., Kril I., et al. . (2016). 5-Ene-4-thiazolidinones induce apoptosis in mammalian leukemia cells. Eur. J. Med. Chem. 117, 33–46. 10.1016/j.ejmech.2016.03.089 PubMed DOI

Shen Z., Song J., Yung B. C., Zhou Z., Wu A., Chen X. (2018). Emerging strategies of cancer therapy based on ferroptosis. Adv. Mater. 30:1704007. 10.1002/adma.201704007 PubMed DOI PMC

Siglienti I., Bendszus M., Kleinschnitz C., Stoll G. (2006). Cytokine profile of iron-laden macrophages: implications for cellular magnetic resonance imaging. J. Neuroimmunol. 173, 166–173. 10.1016/j.jneuroim.2005.11.011 PubMed DOI

Singh M. N., Hemant K. S. Y., Ram M., Shivakumar H. G. (2010). Microencapsulation: a promising technique for controlled drug delivery. Res. Pharm. Sci. 5, 65–77. PubMed PMC

Singh S., Gill A. A. S., Nlooto M., Karpoormath R. (2019). Prostate cancer biomarkers detection using nanoparticles based electrochemical biosensors. Biosens. Bioelectron. 137, 213–221. 10.1016/j.bios.2019.03.065 PubMed DOI

Skumiel A., Kaczmarek-Klinowska M., Timko M., Molcan M., Rajnak M. (2013). Evaluation of power heat losses in multidomain iron particles under the influence of AC magnetic field in RF range. Int. J. Thermophys. 34, 655–666. 10.1007/s10765-012-1380-0 DOI

Skumiel A., Leszczynski B., Molcan M., Timko M. (2016). The comparison of magnetic circuits used in magnetic hyperthermia. J. Magn. Magn. Mater. 420, 177–184. 10.1016/j.jmmm.2016.07.018 DOI

Smith B. R., Gambhir S. S. (2017). Nanomaterials for in vivo imaging. Chem. Rev. 117, 901–986. 10.1021/acs.chemrev.6b00073 PubMed DOI

Soenen S. J. H., Illyes E., Vercauteren D., Braeckmans K., Majer Z., De Smedt S. C., et al. . (2009). The role of nanoparticle concentration-dependent induction of cellular stress in the internalization of non-toxic cationic magnetoliposomes. Biomaterials 30, 6803–6813. 10.1016/j.biomaterials.2009.08.050 PubMed DOI

Suk J. S., Xu Q., Kim N., Hanes J., Ensign L. M. (2016). PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliver. Rev. 99, 28–51. 10.1016/j.addr.2015.09.012 PubMed DOI PMC

Sun K., Gao Z., Zhang Y., Wu H., You C., Wang S., et al. (2018). Enhanced highly toxic reactive oxygen species levels from iron oxide core–shell mesoporous silica nanocarrier-mediated Fenton reactions for cancer therapy. J. Mater. Chem. B 6, 5876–5887. 10.1039/c8tb01731j PubMed DOI

Świętek M., Brož A., Tarasiuk J., Wronski S., Tokarz W., Kozieł A., et al. . (2019a). Carbon nanotube/iron oxide hybrid particles and their PCL-based 3D composites for potential bone regeneration. Mater. Sci. Eng. C 104:109913. 10.1016/j.msec.2019.109913 PubMed DOI

Świętek M., Lu Y.-C., Konefał R., Ferreira L. P., Cruz M. M., Ma Y.-H., et al. . (2019b). Scavenging of reactive oxygen species by phenolic compound-modified maghemite nanoparticles. Beilstein J. Nanotech. 10, 1073–1088. 10.3762/bjnano.10.108 PubMed DOI PMC

Trousil J., Syrová Z., Dal N.-J. K., Rak D., Konefał R., Pavlova E., et al. . (2019). Rifampicin nanoformulation enhances treatment of tuberculosis in zebrafish. Biomacromolecules 20, 1798–1815. 10.1021/acs.biomac.9b00214 PubMed DOI

Truzzi E., Bongio C., Sacchetti F., Maretti E., Montanari M., Iannuccelli V., et al. . (2017). Self-assembled lipid nanoparticles for oral delivery of heparin-coated iron oxide nanoparticles for theranostic purposes. Molecules 22:963. 10.3390/molecules22060963 PubMed DOI PMC

Urbánek T., Jäger E., Jäger A., Hrubý M. (2019). Selectively biodegradable polyesters: nature-inspired construction materials for future biomedical applications. Polymers 11:E1061. 10.3390/polym11061061 PubMed DOI PMC

Walker P. R., Kwast-Welfeld J., Gourdeau H., Leblanc J., Neugebauer W., Sikorska M. (1993). Relationship between apoptosis and the cell cycle in lymphocytes: Roles of protein kinase C, tyrosine phosphorylation, and AP1. Exp Cell Res. 207, 142–151. 10.1006/excr.1993.1173 PubMed DOI

Wang Z.-Q., Stingl L., Morrison C., Jantsch M., Los M., Schulze-Osthoff K., et al. . (1997). PARP is important for genomic stability but dispensable in apoptosis. Genes Dev. 11, 2347–2358. 10.1101/gad.11.18.2347 PubMed DOI PMC

Wu W., He Q., Jian C. (2008). Magnetic iron oxide nanoparticles: synthesis and surface functionalization strategies. Nanoscale Res. Lett. 3, 397–415. 10.1007/s11671-008-9174-9 PubMed DOI PMC

Wydra R. J., Oliver C. E., Anderson K. W., Dziubla T. D., Hilt J. Z. (2015). Accelerated generation of free radicals by iron oxide nanoparticles in the presence of an alternating magnetic field. RSC Adv. 5, 18888–18893. 10.1039/C4RA13564D PubMed DOI PMC

Yang H., Villani R. M., Wang H., Simpson M. J., Roberts M. S., Tang M., et al. . (2018). The role of cellular reactive oxygen species in cancer chemotherapy. J. Exp. Clin. Cancer Res. 37:266. 10.1186/s13046-018-0909-x PubMed DOI PMC

Yokoyama C., Sueyoshi Y., Ema M., Mori Y., Takaishi K., Hisatomi H. (2017). Induction of oxidative stress by anticancer drugs in the presence and absence of cells. Oncol. Lett. 14, 6066–6070. 10.3892/ol.2017.6931 PubMed DOI PMC

Zhang J. H., Xu M. (2000). DNA fragmentation in apoptosis. Cell Res. 10, 205–211. 10.1038/sj.cr.7290049 PubMed DOI

Zhang Y., Huang Y., Li S. (2014). Polymeric micelles: nanocarriers for cancer-targeted drug delivery. AAPS Pharm. Sci. Tech 15, 862–871. 10.1208/s12249-014-0113-z PubMed DOI PMC

Zhao M., Ding X. F., Shen J. Y., Zhang X. P., Ding X. W., Xu B. (2017). Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice. J. Zhejiang Univ. Sci. B. 18, 15–26. 10.1631/jzus.B1600303 PubMed DOI PMC

Zhu L., Zhou Z., Mao H., Yang L. (2017). Magnetic nanoparticles for precision oncology: Theranostic magnetic iron oxide nanoparticles for image-guided and targeted cancer therapy. Nanomedicine 12, 73–87. 10.2217/nnm-2016-0316 PubMed DOI PMC

Zottel A., Videtič Paska A., Jovčevska I. (2019). Nanotechnology meets oncology: nanomaterials in brain cancer research, diagnosis and therapy. Materials 12:1588. 10.3390/ma12101588 PubMed DOI PMC