This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sarcosine in the prostate cancer cells. The prostate cancer targeting was mediated by the AntiSar antibodies decorated surface of the nanocage. Formation of the chitosan nanoparticles was determined using a ninhydrin assay and differential pulse voltammetry. Obtained results showed the strong effect of tripolyphosphine on the nanoparticle formation. The zinc ions affected strong chitosan backbone coiling both in inner and outer chitosan nanoparticle structure. Zinc electrochemical signal depended on the level of the complex formation and the potential shift from -960 to -950 mV. Formed complex is suitable for doxorubicin delivery. It was observed the 20% entrapment efficiency of doxorubicin and strong dependence of drug release after 120 min in the blood environment. The functionality of the designed nanotransporter was proven. The purposed determination showed linear dependence in the concentration range of Anti-sarcosine IgG labeled gold nanoparticles from 0 to 1000 µg/mL and the regression equation was found to be y = 3.8x - 66.7 and R² = 0.99. Performed ELISA confirmed the ability of Anti-sarcosine IgG labeled chitosan nanoparticles with loaded doxorubicin to bind to the sarcosine molecule. Observed hemolytic activity of the nanotransporter was 40%. Inhibition activity of our proposed nanotransporter was evaluated to be 0% on the experimental model of S. cerevisiae. Anti-sarcosine IgG labeled chitosan nanoparticles, with loaded doxorubicin stabilized by Zn ions, are a perspective type of nanocarrier for targeted drug therapy managed by specific interaction with sarcosine and metallothionein for prostate cancer.

Central Laboratory Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno 61200 Brno Czech Republic

Department of Human Pharmacology and Toxicology Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno 61200 Brno Czech Republic

Faculty of Pharmacy Department of Biomedical and Environmental Analyses Wroclaw Medical University 50 556 Wrocław Poland

Prevention Medicals s r o Tovární 342 Butovice 742 13 Studentka Czech Republic

School of Pharmacy and Life Sciences Robert Gordon University Garthdee Road Aberdeen AB10 7QB UK

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Lal N., Dubey J., Gaur P., Verma N., Verma A. Chitosan based in situ forming polyelectrolyte complexes: A potential sustained drug delivery polymeric carrier for high dose drugs. Mater. Sci. Eng. C Mater. Biol. Appl. 2017;79:491–498. doi: 10.1016/j.msec.2017.05.051. PubMed DOI

Sen V.D., Sokolova E.M., Neshev N.I., Kulikov A.V., Pliss E.M. Low molecular chitosan-(poly)nitroxides: Synthesis and evaluation as antioxidants on free radical-induced erythrocyte hemolysis. React. Funct. Polym. 2017;111:53–59. doi: 10.1016/j.reactfunctpolym.2016.12.006. DOI

Niaz T., Nasir H., Shabbir S., Rehman A., Imran M. Polyionic hybrid nano-engineered systems comprising alginate and chitosan for antihypertensive therapeutics. Int. J. Biol. Macromol. 2016;91:180–187. doi: 10.1016/j.ijbiomac.2016.05.055. PubMed DOI

Ellis C.E., Korbutt G.S. Chitosan-based biomaterials for treatment of diabetes. In: Jennings J.A., Bumgardner J.D., editors. Chitosan Based Biomaterials; Volume 2; Tissue Engineering and Therapeutics. Volume 123. Woodhead Publishing; Cambridge, UK: 2017. pp. 91–113.

Pangestuti R., Kim S.-K. Neuroprotective properties of chitosan and its derivatives. Mar. Drugs. 2010;8:2117–2128. doi: 10.3390/md8072117. PubMed DOI PMC

Shariatinia Z., Fazli M. Mechanical properties and antibacterial activities of novel nanobiocomposite films of chitosan and starch. Food Hydrocoll. 2015;46:112–124. doi: 10.1016/j.foodhyd.2014.12.026. DOI

Behera S.S., Das U., Kumar A., Bissoyi A., Singh A.K. Chitosan/TiO2 composite membrane improves proliferation and survival of l929 fibroblast cells: Application in wound dressing and skin regeneration. Int. J. Biol. Macromol. 2017;98:329–340. doi: 10.1016/j.ijbiomac.2017.02.017. PubMed DOI

Park K. Chitosan-gelatin-platelet gel composite scaffold for bone regeneration. J. Controll. Release. 2017;254:137. doi: 10.1016/j.jconrel.2017.05.002. PubMed DOI

Xu H., Matysiak S. Effect of ph on chitosan hydrogel polymer network structure. Chem. Commun. 2017;53:7373–7376. doi: 10.1039/C7CC01826F. PubMed DOI

Desai K.G.H. Chitosan nanoparticles prepared by ionotropic gelation: An overview of recent advances. Crit. Rev. Ther. Drug Carr. Syst. 2016;33:107–158. doi: 10.1615/CritRevTherDrugCarrierSyst.2016014850. PubMed DOI

Huang Y., Lapitsky Y. On the kinetics of chitosan/tripolyphosphate micro- and nanogel aggregation and their effects on particle polydispersity. J. Colloid Interface Sci. 2017;486:27–37. doi: 10.1016/j.jcis.2016.09.050. PubMed DOI

Sacco P., Paoletti S., Cok M., Asaro F., Abrami M., Grassi M., Donati I. Insight into the ionotropic gelation of chitosan using tripolyphosphate and pyrophosphate as cross-linkers. Int. J. Biol. Macromol. 2016;92:476–483. doi: 10.1016/j.ijbiomac.2016.07.056. PubMed DOI

Gan Q., Wang T., Cochrane C., McCarron P. Modulation of surface charge, particle size and morphological properties of chitosan-tpp nanoparticles intended for gene delivery. Colloids Surf. B Biointerfaces. 2005;44:65–73. doi: 10.1016/j.colsurfb.2005.06.001. PubMed DOI

Yata V.K., Ghosh S.S. Investigating structure and fluorescence properties of green fluorescent protein released from chitosan nanoparticles. Mater. Lett. 2012;73:209–211. doi: 10.1016/j.matlet.2012.01.008. DOI

Shanmugam R., Priyanka D.L., Madhuri K., Gowthamarajan K., Karri V., Kumar C.K.A., Murali P. Formulation and characterization of chitosan encapsulated phytoconstituents of curcumin and rutin nanoparticles. Int. J. Biol. Macromol. 2017;104:1807–1812. PubMed

Duarte A.P., Tavares E.J.M., Alves T.V.G., de Moura M.R., da Costa C.E.F., Silva J.O.C., Costa R.M.R. Chitosan nanoparticles as a modified diclofenac drug release system. J. Nanopart. Res. 2017;19 doi: 10.1007/s11051-017-3968-6. DOI

Mendelovits A., Prat T., Gonen Y., Rytwo G. Improved colorimetric determination of chitosan concentrations by dye binding. Appl. Spectrosc. 2012;66:979–982. PubMed

Badawy M.E.I. A new rapid and sensitive spectrophotometric method for determination of a biopolymer chitosan. Int. J. Carbohydr. Chem. 2012;2012:7. doi: 10.1155/2012/139328. DOI

Assa F., Jafarizadeh-Malmiri H., Ajamein H., Vaghari H., Anarjan N., Ahmadi O., Berenjian A. Chitosan magnetic nanoparticles for drug delivery systems. Crit. Rev. Biotechnol. 2017;37:492–509. doi: 10.1080/07388551.2016.1185389. PubMed DOI

Babu A., Ramesh R. Multifaceted applications of chitosan in cancer drug delivery and therapy. Mar. Drugs. 2017;15:96. doi: 10.3390/md15040096. PubMed DOI PMC

Hong S.-C., Yoo S.-Y., Kim H., Lee J. Chitosan-based multifunctional platforms for local delivery of therapeutics. Mar. Drugs. 2017;15:60. doi: 10.3390/md15030060. PubMed DOI PMC

Duttagupta D.S., Jadhav V.M., Kadam V.J. Chitosan: A propitious biopolymer for drug delivery. Curr. Drug Deliv. 2015;12:369–381. doi: 10.2174/1567201812666150310151657. PubMed DOI

Landriscina A., Rosen J., Friedman A.J. Biodegradable chitosan nanoparticles in drug delivery for infectious disease. Nanomedicine. 2015;10:1609–1619. doi: 10.2217/nnm.15.7. PubMed DOI

Sarvaiya J., Agrawal Y.K. Chitosan as a suitable nanocarrier material for anti-alzheimer drug delivery. Int. J. Biol. Macromol. 2015;72:454–465. doi: 10.1016/j.ijbiomac.2014.08.052. PubMed DOI

Lee J., Yun K.S., Choi C.S., Shin S.H., Ban H.S., Rhim T., Lee S.K., Lee K.Y. T cell-specific sirna delivery using antibody-conjugated chitosan nanoparticles. Bioconjug. Chem. 2012;23:1174–1180. doi: 10.1021/bc2006219. PubMed DOI

Sau S., Alsaab H.O., Kashaw S.K., Tatiparti K., Iyer A.K. Advances in antibody-drug conjugates: A new era of targeted cancer therapy. Drug Discov. Today. 2017;22:1547–1556. doi: 10.1016/j.drudis.2017.05.011. PubMed DOI PMC

Sreekumar A., Poisson L.M., Rajendiran T.M., Khan A.P., Cao Q., Yu J., Laxman B., Mehra R., Lonigro R.J., Li Y., et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009;457:910–914. doi: 10.1038/nature07762. PubMed DOI PMC

Kim H.M., Lee Y.K., Koo J.S. Expression of sarcosine-metabolizing enzymes in thyroid cancer. Int. J. Clin. Exp. Pathol. 2016;9:7132–7139.

Cha Y.J., Kim D.H., Jung W.H., Koo J.S. Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer. Int. J. Clin. Exp. Pathol. 2014;7:7824–7833. PubMed PMC

Robinson D.R., Wu Y.M., Lonigro R.J., Vats P., Cobain E., Everett J., Cao X.H., Rabban E., Kumar-Sinha C., Raymond V., et al. Integrative clinical genomics of metastatic cancer. Nature. 2017;548:297–303. doi: 10.1038/nature23306. PubMed DOI PMC

Bizon A., Jedryczko K., Milnerowicz H. The role of metallothionein in oncogenesis and cancer treatment. Postepy Hig. Med. Dosw. 2017;71:98–109. doi: 10.5604/01.3001.0010.3794. PubMed DOI

Krizkova S., Ryvolova M., Hrabeta J., Adam V., Stiborova M., Eckschlager T., Kizek R. Metallothioneins and zinc in cancer diagnosis and therapy. Drug Metab. Rev. 2012;44:287–301. doi: 10.3109/03602532.2012.725414. PubMed DOI

Costello L.C., Franklin R.B. A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Arch. Biochem. Biophys. 2016;611:100–112. doi: 10.1016/j.abb.2016.04.014. PubMed DOI PMC

Sheng S.J., Kraft J.J., Schuster S.M. A specific quantitative colorimetric assay for l-asparagine. Anal. Biochem. 1993;211:242–249. doi: 10.1006/abio.1993.1264. PubMed DOI

Prochazkova S., Vårum K.M., Ostgaard K. Quantitative determination of chitosans by ninhydrin. Carbohydr. Polym. 1999;38:115–122. doi: 10.1016/S0144-8617(98)00108-8. DOI

Leane M.M., Nankervis R., Smith A., Illum L. Use of the ninhydrin assay to measure the release of chitosan from oral solid dosage forms. Int. J. Pharm. 2004;271:241–249. doi: 10.1016/j.ijpharm.2003.11.023. PubMed DOI

Raja M.A., Arif M., Feng C., Zeenat S., Liu C.G. Synthesis and evaluation of ph-sensitive, self-assembled chitosan-based nanoparticles as efficient doxorubicin carriers. J. Biomater. Appl. 2017;31:1182–1195. doi: 10.1177/0885328216681184. PubMed DOI

Lim E.K., Huh Y.M., Yang J., Lee K., Suh J.S., Haam S. Ph-triggered drug-releasing magnetic nanoparticles for cancer therapy guided by molecular imaging by mri. Adv. Mater. 2011;23:2436–2442. doi: 10.1002/adma.201100351. PubMed DOI

Bekale L., Agudelo D., Tajmir-Riahi H.A. Effect of polymer molecular weight on chitosan-protein interaction. Colloids Surf. B Biointerfaces. 2015;125:309–317. doi: 10.1016/j.colsurfb.2014.11.037. PubMed DOI

Docekalova M., Uhlirova D., Stankova M., Kepinska M., Sochor J., Milnerowicz H., Babula P., Fernandez C., Brazdova M., Zidkova J., et al. Characterisation of peroxidase-like activity of thermally synthesized gold nanoparticles; Proceedings of the Nanocon 2016, 8th International Conference on Nanomaterials; Brno, Czech Republic. 19–21 October 2016; Ostrava, Czech Republic: Tanger Ltd.; 2017. pp. 429–434.

Wang Y.B., Zhou J.R., Liu L., Huang C.J., Zhou D.Q., Fu L.L. Characterization and toxicology evaluation of chitosan nanoparticles on the embryonic development of zebrafish, danio rerio. Carbohydr. Polym. 2016;141:204–210. doi: 10.1016/j.carbpol.2016.01.012. PubMed DOI

Hu Y.L., Qi W., Han F., Shao J.Z., Gao J.Q. Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model. Int. J. Nanomed. 2011;6:3351–3359. PubMed PMC

Choi Y.J., Gurunathan S., Kim D., Jang H.S., Park W.J., Cho S.G., Park C., Song H., Seo H.G., Kim J.H. Rapamycin ameliorates chitosan nanoparticle-induced developmental defects of preimplantation embryos in mice. Oncotarget. 2016;7:74658–74677. doi: 10.18632/oncotarget.10813. PubMed DOI PMC

De Salamanca A.E., Diebold Y., Calonge M., Garcia-Vazquez C., Callejo S., Vila A., Alonso M.J. Chitosan nanoparticles as a potential drug delivery system for the ocular surface: Toxicity, uptake mechanism and in vivo tolerance. Investig. Ophthalmol. Vis. Sci. 2006;47:1416–1425. doi: 10.1167/iovs.05-0495. PubMed DOI

Xu Y.R., Asghar S., Yang L., Chen Z.P., Li H.Y., Shi W.W., Li Y.B., Shi Q.Q., Ping Q.N., Xiao Y.Y. Nanoparticles based on chitosan hydrochloride/hyaluronic acid/peg containing curcumin: In Vitro evaluation and pharmacokinetics in rats. Int. J. Biol. Macromol. 2017;102:1083–1091. doi: 10.1016/j.ijbiomac.2017.04.105. PubMed DOI

Liu W., Li L., Ye H., Chen H., Shen W., Zhong Y., Tian T., He H. From saccharomyces cerevisiae to human: The important gene co-expression modules. Biomed. Rep. 2017;7:153–158. doi: 10.3892/br.2017.941. PubMed DOI PMC

Key J., Park K. Multicomponent, tumor-homing chitosan nanoparticles for cancer imaging and therapy. Int. J. Mol. Sci. 2017;18:594. doi: 10.3390/ijms18030594. PubMed DOI PMC

Fu S., Xia J., Wu J. Functional chitosan nanoparticles in cancer treatment. J. Biomed. Nanotechnol. 2016;12:1585–1603. doi: 10.1166/jbn.2016.2228. PubMed DOI

Bugnicourt L., Ladaviere C. Interests of chitosan nanoparticles conically cross-linked with tripolyphosphate for biomedical applications. Prog. Polym. Sci. 2016;60:1–17. doi: 10.1016/j.progpolymsci.2016.06.002. DOI

El-Marakby E.M., Hathout R.M., Taha I., Mansour S., Mortada N.D. A novel serum-stable liver targeted cytotoxic system using valerate-conjugated chitosan nanoparticles surface decorated with glycyrrhizin. Int. J. Pharm. 2017;525:123–138. doi: 10.1016/j.ijpharm.2017.03.081. PubMed DOI

Yu J.X., Wang L., Su L., Ai X.P., Yang H.X. Temperature effects on the electrodeposition of zinc. J. Electrochem. Soc. 2003;150:C19–C23. doi: 10.1149/1.1525269. DOI

Kudr J., Hoai Viet N., Gumulec J., Nejdl L., Blazkova I., Ruttkay-Nedecky B., Hynek D., Kynicky J., Adam V., Kizek R. Simultaneous automatic electrochemical detection of zinc, cadmium, copper and lead ions in environmental samples using a thin-film mercury electrode and an artificial neural network. Sensors. 2015;15:592–610. doi: 10.3390/s150100592. PubMed DOI PMC

Di Martino A., Sedlarik V. Amphiphilic chitosan-grafted-functionalized polylactic acid based nanoparticles as a delivery system for doxorubicin and temozolomide co-therapy. Int. J. Pharm. 2014;474:134–145. doi: 10.1016/j.ijpharm.2014.08.014. PubMed DOI

Xiong W., Li L., Wang Y., Yu Y., Wang S., Gao Y., Liang Y., Zhang G., Pan W., Yang X. Design and evaluation of a novel potential carrier for a hydrophilic antitumor drug: Auricularia auricular polysaccharide-chitosan nanoparticles as a delivery system for doxorubicin hydrochloride. Int. J. Pharm. 2016;511:267–275. doi: 10.1016/j.ijpharm.2016.07.026. PubMed DOI

Janes K.A., Fresneau M.P., Marazuela A., Fabra A., Alonso M.J. Chitosan nanoparticles as delivery systems for doxorubicin. J. Controll. Release. 2001;73:255–267. doi: 10.1016/S0168-3659(01)00294-2. PubMed DOI

Soares P.I.P., Sousa A.I., Silva J.C., Ferreira I.M.M., Novo C.M.M., Borges J.P. Chitosan-based nanoparticles as drug delivery systems for doxorubicin: Optimization and modelling. Carbohydr. Polym. 2016;147:304–312. doi: 10.1016/j.carbpol.2016.03.028. PubMed DOI

Anitha A., Deepagan V.G., Rani V.V.D., Menon D., Nair S.V., Jayakumar R. Preparation, characterization, in vitro drug release and biological studies of curcumin loaded dextran sulphate-chitosan nanoparticles. Carbohydr. Polym. 2011;84:1158–1164. doi: 10.1016/j.carbpol.2011.01.005. DOI

Esfandiarpour-Boroujeni S., Bagheri-Khoulenjani S., Mirzadeh H., Amanpour S. Fabrication and study of curcumin loaded nanoparticles based on folate-chitosan for breast cancer therapy application. Carbohydr. Polym. 2017;168:14–21. doi: 10.1016/j.carbpol.2017.03.031. PubMed DOI

Yang C.L., Chen J.P., Wei K.C., Chen J.Y., Huang C.W., Liao Z.X. Release of doxorubicin by a folate-grafted, chitosan-coated magnetic nanoparticle. Nanomaterials. 2017;7:85. doi: 10.3390/nano7040085. PubMed DOI PMC

Chen X., Zhu X.Y., Li L., Xian G.J., Wang W., Ma D.W., Xie L. Investigation on novel chitosan nanoparticle-aptamer complexes targeting tgf-beta receptor II. Int. J. Pharm. 2013;456:499–507. doi: 10.1016/j.ijpharm.2013.08.028. PubMed DOI

Arya G., Vandana M., Acharya S., Sahoo S.K. Enhanced antiproliferative activity of herceptin (HER2)-conjugated gemcitabine-loaded chitosan nanoparticle in pancreatic cancer therapy. Nanomed. Nanotechnol. Biol. Med. 2011;7:859–870. doi: 10.1016/j.nano.2011.03.009. PubMed DOI

Zhu R., Zhang C.-G., Liu Y., Yuan Z.-Q., Chen W.-L., Yang S.-D., Li J.-Z., Zhu W.-J., Zhou X.-F., You B.-G., et al. Cd147 monoclonal antibody mediated by chitosan nanoparticles loaded with α-hederin enhances antineoplastic activity and cellular uptake in liver cancer cells. Sci. Rep. 2015;5:17904. doi: 10.1038/srep17904. PubMed DOI PMC

Yousefpour P., Atyabi F., Vasheghani-Farahani E., Movahedi A.-A.M., Dinarvand R. Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-her2 trastuzumab. Int. J. Nanomed. 2011;6:1977–1990. PubMed PMC

Zhao L., Yang G., Shi Y., Su C., Chang J. Co-delivery of gefitinib and chloroquine by chitosan nanoparticles for overcoming the drug acquired resistance. J. Nanobiotechnol. 2015;13 doi: 10.1186/s12951-015-0121-5. PubMed DOI PMC

Shargh V.H., Hondermarck H., Liang M. Antibody-targeted biodegradable nanoparticles for cancer therapy. Nanomedicine. 2016;11:63–79. doi: 10.2217/nnm.15.186. PubMed DOI

Goodall S., Jones M.L., Mahler S. Monoclonal antibody-targeted polymeric nanoparticles for cancer therapy-future prospects. J. Chem. Technol. Biotechnol. 2015;90:1169–1176. doi: 10.1002/jctb.4555. DOI

Zhu Y., Choi S.H., Shah K. Multifunctional receptor-targeting antibodies for cancer therapy. Lancet Oncol. 2015;16:e543–e554. doi: 10.1016/S1470-2045(15)00039-X. PubMed DOI

Svirshchevskaya E.V., Zubareva A.A., Boyko A.A., Shustova O.A., Grechikhina M.V., Shagdarova B.T., Varlamov V.P. Analysis of toxicity and biocompatibility of chitosan derivatives with different physico-chemical properties. Appl. Biochem. Microbiol. 2016;52:483–490. doi: 10.1134/S000368381605015X. PubMed DOI

Zubareva A., Shagdarova B., Varlamov V., Kashirina E., Svirshchevskaya E. Penetration and toxicity of chitosan and its derivatives. Eur. Polym. J. 2017;93:743–749. doi: 10.1016/j.eurpolymj.2017.04.021. DOI

Saenko Y.V., Shutov A.M., Rastorgueva E.V. Doxorubicin and menadione decrease cell proliferation of saccharomyces cerevisiae by different mechanisms. Cell Tissue Biol. 2010;4:332–336. doi: 10.1134/S1990519X1004005X. PubMed DOI

Nguyen T.T.T., Lim Y.J., Fan M.H.M., Jackson R.A., Lim K.K., Ang W.H., Ban K.H.K., Chen E.S. Calcium modulation of doxorubicin cytotoxicity in yeast and human cells. Genes Cells. 2016;21:226–240. doi: 10.1111/gtc.12346. PubMed DOI

Westmoreland T.J., Wickramasekara S.M., Guo A.Y., Selim A.L., Winsor T.S., Greenleaf A.L., Blackwell K.L., Olson J.A., Marks J.R., Bennett C.B. Comparative genome-wide screening identifies a conserved doxorubicin repair network that is diploid specific in saccharomyces cerevisiae. PLoS ONE. 2009;4:e5830. doi: 10.1371/journal.pone.0005830. PubMed DOI PMC

Demir A.B., Koc A. High-copy overexpression screening reveals pdr5 as the main doxorubicin resistance gene in yeast. PLoS ONE. 2015;10:e0148108. doi: 10.1371/journal.pone.0145108. PubMed DOI PMC

Xia L., Jaafar L., Cashikar A., Flores-Rozas H. Identification of genes required for protection from doxorubicin by a genome-wide screen in saccharomyces cerevisiae. Cancer Res. 2007;67:11411–11418. doi: 10.1158/0008-5472.CAN-07-2399. PubMed DOI PMC

Hooda V., Archita Enzymes loaded chitosan/coconut fibre/zinc oxide nanoparticles strip for polyamine determination. Food Chem. 2018;239:1100–1109. doi: 10.1016/j.foodchem.2017.07.057. PubMed DOI

Deshpande P., Dapkekar A., Oak M.D., Paknikar K.M., Rajwade J.M. Zinc complexed chitosan/tpp nanoparticles: A promising micronutrient nanocarrier suited for foliar application. Carbohydr. Polym. 2017;165:394–401. doi: 10.1016/j.carbpol.2017.02.061. PubMed DOI

Al-Naamani L., Dobretsov S., Dutta J., Burgess J.G. Chitosan-zinc oxide nanocomposite coatings for the prevention of marine biofouling. Chemosphere. 2017;168:408–417. doi: 10.1016/j.chemosphere.2016.10.033. PubMed DOI

Noshirvani N., Ghanbarzadeh B., Mokarram R.R., Hashemi M., Coma V. Preparation and characterization of active emulsified films based on chitosan-carboxymethyl cellulose containing zinc oxide nano particles. Int. J. Biol. Macromol. 2017;99:530–538. doi: 10.1016/j.ijbiomac.2017.03.007. PubMed DOI

Wang H.J., Liu S.L., Zhang A.K., Li K.W., Oderinde O., Yao F., Fu G.D. Zinc ion-induced formation of hierarchical N-succinyl chitosan film. J. Appl. Polym. Sci. 2017;134 doi: 10.1002/app.44664. DOI

Costello L.C., Franklin R.B., Zou J., Feng P., Bok R., Swanson M.G., Kurhanewicz J. Human prostate cancer zip1/zinc/citrate genetic/metabolic relationship in the tramp prostate cancer animal model. Cancer Biol. Ther. 2011;12:1078–1084. doi: 10.4161/cbt.12.12.18367. PubMed DOI PMC

Dambal S., Baumann B., McCray T., Williams L., Richards Z., Deaton R., Prins G.S., Nonn L. The mir-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts. Sci. Rep. 2017;7:7704. doi: 10.1038/s41598-017-07979-y. PubMed DOI PMC

Jing L., Li L.Z., Zhao J., Sun Z.W., Peng S.Q. Zinc-induced metallothionein overexpression prevents doxorubicin toxicity in cardiomyocytes by regulating the peroxiredoxins. Xenobiotica. 2016;46:715–725. doi: 10.3109/00498254.2015.1110760. PubMed DOI

Franklin R.B., Costello L.C. The important role of the apoptotic effects of zinc in the development of cancers. J. Cell. Biochem. 2009;106:750–757. doi: 10.1002/jcb.22049. PubMed DOI PMC

Pang S.-T., Lin F.-W., Chuang C.-K., Yang H.-W. Co-delivery of docetaxel and p44/42 mapk sirna using PSMA antibody-conjugated BSA-PEI layer-by-layer nanoparticles for prostate cancer target therapy. Macromol. Biosci. 2017;17 doi: 10.1002/mabi.201600421. PubMed DOI

Daniels-Wells T.R., Helguera G., Leuchter R.K., Quintero R., Kozman M., Rodriguez J.A., Ortiz-Sanchez E., Martinez-Maza O., Schultes B.C., Nicodemus C.F., et al. A novel ige antibody targeting the prostate-specific antigen as a potential prostate cancer therapy. BMC Cancer. 2013;13:195. doi: 10.1186/1471-2407-13-195. PubMed DOI PMC

Nagesh P.K.B., Johnson N., Boya V.K.N., Chowdhury P., Ganju A., Hafeez B., Khan S., Jaggi M., Chauhan S.C., Yallapu M.M. PSMA antibody functionalized docetaxel-loaded magnetic nanoparticles for prostate cancer therapy. Cancer Res. 2016;76 doi: 10.1158/1538-7445.AM2016-1312. DOI

Lukey M.J., Katt W.P., Cerione R.A. Targeting amino acid metabolism for cancer therapy. Drug Discov. Today. 2017;22:796–804. doi: 10.1016/j.drudis.2016.12.003. PubMed DOI PMC

Roy D., Sheng G.Y., Herve S., Carvalho E., Mahanty A., Yuan S.T., Sun L. Interplay between cancer cell cycle and metabolism: Challenges, targets and therapeutic opportunities. Biomed. Pharmacother. 2017;89:288–296. doi: 10.1016/j.biopha.2017.01.019. PubMed DOI

Sidaway P. Prostate cancer: Targeting lipid metabolism. Nat. Rev. Urol. 2017;14:196. doi: 10.1038/nrurol.2017.28. PubMed DOI

Amelio I., Cutruzzola F., Antonov A., Agostini M., Melino G. Serine and glycine metabolism in cancer. Trends Biochem. Sci. 2014;39:191–198. doi: 10.1016/j.tibs.2014.02.004. PubMed DOI PMC

Jain M., Nilsson R., Sharma S., Madhusudhan N., Kitami T., Souza A.L., Kafri R., Kirschner M.W., Clish C.B., Mootha V.K. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science. 2012;336:1040–1044. doi: 10.1126/science.1218595. PubMed DOI PMC

Heger Z., Polanska H., Rodrigo M.A.M., Guran R., Kulich P., Kopel P., Masarik M., Eckschlager T., Stiborova M., Kizek R., et al. Prostate tumor attenuation in the nu/nu murine model due to anti-sarcosine antibodies in folate-targeted liposomes. Sci. Rep. 2016;6:33379. doi: 10.1038/srep33379. PubMed DOI PMC

Sabnis S., Block L.H. Chitosan as an enabling excipient for drug delivery systems. I. Molecular modifications. Int. J. Biol. Macromol. 2000;27:181–186. doi: 10.1016/S0141-8130(00)00118-5. PubMed DOI

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