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Nanomedicines in the treatment of colon cancer: a focus on metallodrugs

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Abstract

Worldwide, colon cancer (CC) represents the fourth most common type of cancer and the fifth major cause of cancer-associated deaths. Surgical resection is considered the standard therapeutic choice for CC in early stages. However, in latter stages of the disease, adjuvant chemotherapy is essential for an appropriate management of this pathology. Metal-based complexes displaying cytotoxic properties towards tumor cells emerge as potential chemotherapeutic options. One metallodrug, oxaliplatin, was already approved for clinical use, playing an important role in the treatment of CC patients. Unfortunately, most of the newly designed metal-based complexes exhibit lack of selectivity against cancer cells, low solubility and permeability, high dose-limiting toxicity, and emergence of resistances. Nanodelivery systems enable the incorporation of metallodrugs at adequate payloads, solving the above-referred drawbacks. Moreover, drug delivery systems, depending on their physicochemical properties, are able to release the incorporated material preferentially at affected tissues/organs, enhancing the therapeutic activity in vivo, with concomitant fewer side effects. In this review, the general features and therapeutic management of CC will be addressed, with a special focus on preclinical or clinical studies using metal-based compounds. Furthermore, the use of different nanodelivery systems will also be described as tools to potentiate the therapeutic index of metallodrugs for the management of CC.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Nabi K, Le A. The intratumoral heterogeneity of cancer metabolism. Adv Exp Med Biol. 2018;1063:131–45.

    Article  CAS  PubMed  Google Scholar 

  2. Mattiuzzi C, Lippi G. Current Cancer Epidemiology glossary. J Epidemiol Glob Health. 2019;9:217–22.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Li F, Lai M. Colorectal cancer, one entity or three. J Zhejiang Univ Sci B. 2009;10:219–29.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Cappell MS. Pathophysiology, clinical presentation, and management of colon cancer. Gastroenterol Clin North Am. 2008;37:1–24.

    Article  PubMed  Google Scholar 

  5. Mattiuzzi C, Sanchis-Gomar F, Lippi G. Concise update on colorectal cancer epidemiology. Ann Transl Med. 2019;7:609.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ahmed M. Colon cancer: a clinician’s perspective in 2019. Gastroenterol Res. 2020;13:1–10.

    Article  Google Scholar 

  7. Ilyas M, Straub J, Tomlinson IPM, Bodmer WF. Genetic pathways in colorectal and other cancers. Eur J Cancer. 1999;35:1986–2002.

    Article  CAS  PubMed  Google Scholar 

  8. Balchen V, Simon K. Colorectal cancer development and advances in screening. Clin Interv Aging. 2016;11:967–76.

    Article  Google Scholar 

  9. Virk GS, Jafri M, Mehdi S, Ashley C. Staging and survival of colorectal cancer (CRC) in octogenarians: Nationwide Study of US Veterans. J Gastrointest Oncol. 2018;10:12–8.

    Article  Google Scholar 

  10. Johns Hopkins Colon Cancer Center. Sporadic (Nonhereditary) Colorectal Cancer: Introduction [Internet]. 2013 [cited 2020 Aug 4]. Available from: https://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/small_large_intestine/sporadic_nonhereditary_colorectal_cancer.pdf.

  11. American Cancer Society. Survival Rates for Colorectal Cancer [Internet]. 2020 [cited 2020 Aug 26]. Available from: https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/survival-rates.html.

  12. Pan P, Yu J, Wang LS. Colon cancer: what we eat. Surg Oncol Clin N Am. 2018;27:243–67.

    Article  PubMed  Google Scholar 

  13. Testino G, Leone S, Sumberaz A, Borro P. Alcohol and cancer. Alcohol Clin Exp Res. 2015;39:2261–2261.

    Article  PubMed  Google Scholar 

  14. Parajuli R, Bjerkaas E, Tverdal A, Selmer R, Le ML, Weiderpass E, et al. The increased risk of colon cancer due to cigarette smoking may be greater in women than men. Cancer Epidemiol Biomarkers Prev. 2013;22:862–71.

    Article  PubMed  Google Scholar 

  15. Baena R, Salinas P. Diet and colorectal cancer. Maturitas. 2015;80:258–64.

    Article  CAS  PubMed  Google Scholar 

  16. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  17. GLOBOCAN [Internet]. 2020 [cited 2020 Aug 31]. Available from: https://gco.iarc.fr/.

  18. Stoffel EM, Murphy CC. Epidemiology and mechanisms of the increasing incidence of colon and rectal cancers in young adults. Gastroenterology. 2020;158:341–53.

    Article  PubMed  Google Scholar 

  19. Schreuders EH, Ruco A, Rabeneck L, Schoen RE, Sung JJY, Young GP, et al. Colorectal cancer screening: a global overview of existing programmes. Gut. 2015;64:1637–49.

    Article  PubMed  Google Scholar 

  20. Burt RW. Colon cancer screening continues as pivotal to cancer prevention. J Natl Compr Cancer Netw. 2013;11:1457–8.

    Article  Google Scholar 

  21. Vogel JD, Eskicioglu C, Weiser MR, Feingold DL, Steele SR. The American Society of Colon and Rectal Surgeons clinical practice guidelines for the treatment of colon cancer. Dis Colon Rectum. 2017;60:999–1017.

    Article  PubMed  Google Scholar 

  22. Labianca R, Beretta GD, Kildani B, Milesi L, Merlin F, Mosconi S, et al. Colon cancer. Crit Rev Oncol Hematol. 2010;74:106–33.

    Article  PubMed  Google Scholar 

  23. Hagan S, Orr MCM, Doyle B. Targeted therapies in colorectal cancer—an integrative view by PPPM. EPMA J. 2013;4:3.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gulbake A, Jain A, Jain A, Jain A, Jain SK. Insight to drug delivery aspects for colorectal cancer. World J Gastroenterol. 2016;22:582–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. National Cancer Institute. Colon Cancer Treatment (PDQ®): Health Professional Version. [Internet]. Bethesda (MD); 2020 [cited 2020 Aug 10]. Available from: https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq.

  26. Hodgkinson N, Kruger CA, Abrahamse H. Targeted photodynamic therapy as potential treatment modality for the eradication of colon cancer and colon cancer stem cells. Tumor Biol. 2017;39:1010428317734691.

    Article  Google Scholar 

  27. Willett CG, Duda DG, Czito BG, Bendell JC, Clark JW, Jain RK. Targeted therapy in rectal cancer. Oncology. 2007;21:1055–65.

    PubMed  Google Scholar 

  28. Ashburn JH, Kalady MF. Radiation-induced problems in colorectal surgery. Clin Colon Rectal Surg. 2016;29:85–91.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Bender U, Rho YS, Barrera I, Aghajanyan S, Acoba J, Kavan P. Adjuvant therapy for stages II and III colon cancer: risk stratification, treatment duration, and future directions. Curr Oncol. 2019;26:S43-52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gelibter AJ, Caponnetto S, Urbano F, Emiliani A, Scagnoli S, Sirgiovanni G, et al. Adjuvant chemotherapy in resected colon cancer: When, how and how long? Surg Oncol Elsevier. 2019;30:100–7.

    Article  Google Scholar 

  31. Chan GHJ, Chee CE. Making sense of adjuvant chemotherapy in colorectal cancer. J Gastrointest Oncol. 2019;10:1183–92.

    Article  PubMed  PubMed Central  Google Scholar 

  32. McKeown E, Nelson DW, Johnson EK, Maykel JA, Stojadinovic A, Nissan A, et al. Current approaches and challenges for monitoring treatment response in colon and rectal cancer. J Cancer. 2014;5:31–43.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kotelevets L, Chastre E, Desmaële D, Couvreur P. Nanotechnologies for the treatment of colon cancer: from old drugs to new hope. Int J Pharm. 2016;514:24–40.

    Article  CAS  PubMed  Google Scholar 

  34. Van Der Jeught K, Xu HC, Li YJ, Lu XB, Ji G. Drug resistance and new therapies in colorectal cancer. World J Gastroenterol. 2018;24:3834–48.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ott I, Gust R. Non platinum metal complexes as anti-cancer drugs. Arch Pharm (Weinheim). 2007;340:117–26.

    Article  CAS  Google Scholar 

  36. Martín J, Alés MR, Asuero GA. An overview on ligands of therapeutically interest. Pharm Pharmacol Int J. 2018;6:198–214.

    Google Scholar 

  37. Brenner H, Kloor M, Pox CP. Colorectal cancer Lancet England. 2014;383:1490–502.

    Google Scholar 

  38. National Cancer Institute. Drugs approved for colon and rectal cancer [Internet]. 2019 [cited 2020 Aug 2]. Available from: https://www.cancer.gov/about-cancer/treatment/drugs/colorectal.

  39. Wu C. Systemic Therapy for colon cancer. Surg Oncol Clin N Am. Elsevier Inc; 2018;27:235–42.

  40. Culy CR, Clemett D, Wiseman LR. Oxaliplatin drugs. 2000;60:895–924.

    Article  CAS  PubMed  Google Scholar 

  41. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14:1208–15.

    Article  CAS  PubMed  Google Scholar 

  42. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371:1007–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol England. 2015;16:1306–15.

    Article  CAS  Google Scholar 

  44. Mir M, Ahmed N, Rehman AU. Recent applications of PLGA based nanostructures in drug delivery. Colloids Surf B Biointerfaces. 2017;159:217–31.

    Article  CAS  PubMed  Google Scholar 

  45. Pinho JO, Matias M, Gaspar MM. Emergent nanotechnological strategies for systemic chemotherapy against melanoma. Nanomaterials. 2019;9:1455.

    Article  CAS  Google Scholar 

  46. de Almeida A, Oliveira BL, Correia JDG, Soveral G, Casini A. Emerging protein targets for metal-based pharmaceutical agents: an update. Coord Chem Rev. 2013;257:2689–704.

    Article  Google Scholar 

  47. Sullivan MP, Holtkamp HU, Hartinger CG. Antitumor Metallodrugs that Target Proteins. In: Sigel A, Sigel H, Freisinger E, Sigel RKO, editors. Met Dev Action Anticancer Agents. Berlin: De Gruyter; 2018. p. 351–86.

    Chapter  Google Scholar 

  48. Ghosh S. Cisplatin: the first metal based anticancer drug. Bioorg Chem. 2019;88:102925.

    Article  CAS  PubMed  Google Scholar 

  49. Wong E, Giandornenico CM. Current status of platinum-based antitumor drugs. Chem Rev. 1999;99:2451–66.

    Article  CAS  PubMed  Google Scholar 

  50. Ho YP, Au-Yeung SCF, To KKW. Platinum-based anticancer agents: Innovative design strategies and biological perspectives. Med Res Rev. 2003;23:633–55.

    Article  CAS  PubMed  Google Scholar 

  51. Frezza M, Hindo S, Chen D, Davenport A, Schmitt S, Tomco D, et al. Novel metals and metal complexes as platforms for cancer therapy. Curr Pharm Des. 2010;16:1813–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ndagi U, Mhlongo N, Soliman M. Metal complexes in cancer therapy - an update from drug design perspective. Drug Des Devel Ther. 2017;11:599–616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Casini A, Sun RWY, Ott I. Medicinal chemistry of gold anticancer metallodrugs. In: Sigel A, Sigel H, Freisinger E, Sigel R, editors. Met Dev Action Anticancer Agents. Berlin, Boston: De Gruyter; 2018. p. 199–217.

    Chapter  Google Scholar 

  54. Scheffler H, You Y, Ott I. Comparative studies on the cytotoxicity, cellular and nuclear uptake of a series of chloro gold(I) phosphine complexes. Polyhedron. 2010;29:66–9.

    Article  CAS  Google Scholar 

  55. Tong KC, Lok CN, Wan PK, Hu D, Fung YME, Chang XY, et al. An anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols. Proc Natl Acad Sci. 2020;117:1321–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Miranda S, Vergara E, Mohr F, de Vos D, Cerrada E, Mendía A, et al. Synthesis, characterization, and in vitro cytotoxicity of some gold(I) and trans platinum(II) thionate complexes containing water-soluble PTA and DAPTA ligands. X-ray crystal structures of [Au(SC4H3N2)(PTA)], trans-[Pt(SC4H3N2)2(PTA)2], trans-[Pt(SC5H4N)2. Inorg Chem Am Chem Soc. 2008;47:5641–8.

    Article  CAS  Google Scholar 

  57. Gandin V, Fernandes AP, Rigobello MP, Dani B, Sorrentino F, Tisato F, et al. Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase. Biochem Pharmacol. 2010;79:90–101.

    Article  CAS  PubMed  Google Scholar 

  58. Santini C, Pellei M, Gandin V, Porchia M, Tisato F, Marzano C. Advances in copper complexes as anticancer agents. Chem Rev. 2014;114:815–62.

    Article  CAS  PubMed  Google Scholar 

  59. Montagner D, Fresch B, Browne K, Gandin V, Erxleben A. A Cu(ii) complex targeting the translocator protein: in vitro and in vivo antitumor potential and mechanistic insights. Chem Commun. 2017;53:134–7.

    Article  CAS  Google Scholar 

  60. Leite SMG, Lima LMP, Gama S, Mendes F, Orio M, Bento I, et al. Copper(II) complexes of phenanthroline and histidine containing ligands: synthesis, characterization and evaluation of their DNA cleavage and cytotoxic activity. Inorg Chem. 2016;55:11801–14.

    Article  CAS  PubMed  Google Scholar 

  61. Nunes CJ, Otake AH, Bustos SO, Fazzi RB, Chammas R, Da Costa Ferreira AM. Unlike reactivity of mono- and binuclear imine-copper(II) complexes toward melanoma cells via a tyrosinase-dependent mechanism. Chem Biol Interact. 2019;311:108789.

    Article  CAS  PubMed  Google Scholar 

  62. Bacher F, Wittmann C, Nové M, Spengler G, Marć MA, Enyedy EA, et al. Novel latonduine derived proligands and their copper(II) complexes show cytotoxicity in the nanomolar range in human colon adenocarcinoma cells and: in vitro cancer selectivity. Dalt Trans. 2019;48:10464–78.

    Article  CAS  Google Scholar 

  63. Gandin V, Pellei M, Tisato F, Porchia M, Santini C, Marzano C. A novel copper complex induces paraptosis in colon cancer cellsviathe activation of ER stress signalling. J Cell Mol Med. 2012;16:142–51.

    Article  CAS  PubMed  Google Scholar 

  64. Pinho JO, Amaral JD, Castro RE, Rodrigues CMP, Casini A, Soveral G, et al. Copper complex nanoformulations featuring highly promising therapeutic potential in murine melanoma models. Nanomedicine. 2019;14:835–50.

    Article  CAS  PubMed  Google Scholar 

  65. Nave M, Castro RE, Rodrigues CMP, Casini A, Soveral G, Gaspar MM. Nanoformulations of a potent copper-based aquaporin inhibitor with cytotoxic effect against cancer cells. Nanomedicine. 2016;11:1817–30.

    Article  CAS  PubMed  Google Scholar 

  66. Köpf-Maier P, Köpf H, Neuse EW. Ferricenium complexes: a new type of water-soluble antitumor agent. J Cancer Res Clin Oncol. 1984;108:336–40.

    Article  PubMed  Google Scholar 

  67. Estrada-Montaño AS, Ryabov AD, Gries A, Gaiddon C, Le Lagadec R. Iron(III) pincer complexes as a strategy for anticancer studies. Eur J Inorg Chem. 2017;2017:1673–8.

    Article  Google Scholar 

  68. Florindo PR, Pereira DM, Borralho PM, Rodrigues CMP, Piedade MFM, Fernandes AC. Cyclopentadienyl–ruthenium(II) and iron(II) organometallic compounds with carbohydrate derivative ligands as good colorectal anticancer agents. J Med Chem. 2015;58:4339–47.

    Article  CAS  PubMed  Google Scholar 

  69. Şen B, Kalhan HK, Demir V, Güler EE, Kayalı HA, Subaşı E. Crystal structures, spectroscopic properties of new cobalt(II), nickel(II), zinc(II) and palladium(II) complexes derived from 2-acetyl-5-chloro thiophene thiosemicarbazone: anticancer evaluation. Mater Sci Eng C. 2019;98:550–9.

    Article  Google Scholar 

  70. Pessoa JC, Etcheverry S, Gambino D. Vanadium compounds in medicine. Coord Chem Rev. 2015;301–302:24–48.

    Article  Google Scholar 

  71. Kioseoglou E, Petanidis S, Gabriel C, Salifoglou A. The chemistry and biology of vanadium compounds in cancer therapeutics. Coord Chem Rev. 2015;301–302:87–105.

    Article  Google Scholar 

  72. León IE, Cadavid-Vargas JF, Tiscornia I, Porro V, Castelli S, Katkar P, et al. Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model. J Biol Inorg Chem. 2015;20:1175–91.

    Article  PubMed  Google Scholar 

  73. Kowalski S, Wyrzykowski D, Inkielewicz-Stępniak I. Molecular and cellular mechanisms of cytotoxic activity of vanadium compounds against cancer cells. Molecules. 2020;25:1757.

    Article  CAS  PubMed Central  Google Scholar 

  74. Reytman L, Hochman J, Tshuva EY. Anticancer diaminotris(phenolato) vanadium(V) complexes: ligand-metal interplay. J Coord Chem. 2018;71:2003–11.

    Article  CAS  Google Scholar 

  75. Rana SR, McCaffrey V, Rabquer BJ. Vanadium complex induced cancer cell death via RIPK3 activated necroptosis. FASEB J. 2018;31:876.6.

    Google Scholar 

  76. Sinha A, Banerjee K, Banerjee A, Sarkar A, Ahir M, Adhikary A, et al. Induction of apoptosis in human colorectal cancer cell line, HCT-116 by a vanadium- Schiff base complex. Biomed Pharmacother. 2017;92:509–18.

    Article  CAS  PubMed  Google Scholar 

  77. Sanna D, Ugone V, Micera G, Buglyó P, Bíró L, Garribba E. Speciation in human blood of Metvan, a vanadium based potential anti-tumor drug. Dalt Trans. 2017;46:8950–67.

    Article  CAS  Google Scholar 

  78. León IE, Ruiz MC, Franca CA, Parajón-Costa BS, Baran EJ. Metvan, bis(4,7-Dimethyl-1,10-phenanthroline)sulfatooxidovanadium(IV): DFT and spectroscopic study—antitumor action on human bone and colorectal cancer cell lines. Biol Trace Elem Res. 2019;191:81–7.

    Article  PubMed  Google Scholar 

  79. Sinha A, Banerjee K, Banerjee A, Das S, Choudhuri SK. Synthesis, characterization and biological evaluation of a novel vanadium complex as a possible anticancer agent. J Organomet Chem. 2014;772–773:34–41.

    Article  Google Scholar 

  80. Bratsos I, Gianferrara T, Alessio E, Hartinger CG, Jakupec MA, Keppler BK. Ruthenium and other non-platinum anticancer compounds. In: Alessio E, editor. Bioinorg Med Chem. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2011. p. 151–74.

    Chapter  Google Scholar 

  81. Lazarević T, Rilak A, Bugarčić ŽD. Platinum, palladium, gold and ruthenium complexes as anticancer agents: current clinical uses, cytotoxicity studies and future perspectives. Eur J Med Chem. 2017;142:8–31.

    Article  PubMed  Google Scholar 

  82. Carter R, Westhorpe A, Romero M, Habtemariam A, Gallevo C, Bark Y, et al. Radiosensitisation of human colorectal cancer cells by ruthenium(II) arene anticancer complexes. Sci Rep. 2016;6:20596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ma DL, Wu C, Wu KJ, Leung CH. Iridium(III) complexes targeting apoptotic cell death in cancer cells. Molecules. 2019;24:2739.

    Article  CAS  PubMed Central  Google Scholar 

  84. Lord RM, Zegke M, Henderson IR, Pask CM, Shepherd HJ, McGowan PC. β-Ketoiminato iridium(III) organometallic complexes: selective cytotoxicity towards colorectal cancer cells HCT116 p53 -/-. Chem - A Eur J. 2019;25:495–500.

    Article  CAS  Google Scholar 

  85. Fischer-Fodor E, Mikláš R, Rišiaňová L, Cenariu M, Grosu IG, Virag P, et al. Novel palladium(II) complexes that influence prominin-1/CD133 expression and stem cell factor release in tumor cells. Molecules. 2017;22:561.

    Article  PubMed Central  Google Scholar 

  86. Rajpoot K, Jain SK. Colorectal cancer-targeted delivery of oxaliplatin via folic acid-grafted solid lipid nanoparticles: preparation, optimization, and in vitro evaluation. Artif Cells, Nanomedicine, Biotechnol. 2018;46:1236–47.

    Article  CAS  Google Scholar 

  87. Mjos KD, Orvig C. Metallodrugs in medicinal inorganic chemistry. Chem Rev. 2014;114:4540–63.

    Article  CAS  PubMed  Google Scholar 

  88. Stewart DJ. Mechanisms of resistance to cisplatin and carboplatin. Crit Rev Oncol Hematol. 2007;63:12–31.

    Article  PubMed  Google Scholar 

  89. Bayón-Cordero L, Alkorta I, Arana L. Application of solid lipid nanoparticles to improve the efficiency of anticancer drugs. Nanomaterials. 2019;9:474.

    Article  PubMed Central  Google Scholar 

  90. Makovec T. Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol. 2019;53:148–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Komarova NL, Wodarz D. Drug resistance in cancer: principles of emergence and prevention. Proc Natl Acad Sci. 2005;102:9714–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Sguizzato M, Cortesi R, Gallerani E, Drechsler M, Marvelli L, Mariani P, et al. Solid lipid nanoparticles for the delivery of 1,3,5-triaza-7-phosphaadamantane (PTA) platinum (II) carboxylates. Mater Sci Eng C. 2017;74:357–64.

    Article  CAS  Google Scholar 

  93. Belfiore L, Saunders DN, Ranson M, Thurecht KJ, Storm G, Vine KL. Towards clinical translation of ligand-functionalized liposomes in targeted cancer therapy: challenges and opportunities. J Control Release. 2018;277:1–13.

    Article  CAS  PubMed  Google Scholar 

  94. Sanna V, Pala N, Sechi M. Targeted therapy using nanotechnology: focus on cancer. Int J Nanomedicine. 2014;9:467–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Silva CO, Pinho JO, Lopes JM, Almeida AJ, Gaspar MM, Reis C. Current trends in cancer nanotheranostics: metallic, polymeric, and lipid-based systems. Pharmaceutics. 2019;11:22.

    Article  CAS  PubMed Central  Google Scholar 

  96. Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16:71.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Griffin BT, Guo J, Presas E, Donovan MD, Alonso MJ, O’Driscoll CM. Pharmacokinetic, pharmacodynamic and biodistribution following oral administration of nanocarriers containing peptide and protein drugs. Adv Drug Deliv Rev. 2016;106:367–80.

    Article  CAS  PubMed  Google Scholar 

  98. Durán-Lobato M, Niu Z, Alonso MJ. Oral delivery of biologics for precision medicine. Adv Mater. 2020;32:1901935.

    Article  Google Scholar 

  99. Attia MF, Anton N, Wallyn J, Omran Z, Vandamme TF. An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites. J Pharm Pharmacol. 2019;71:1185–98.

    Article  CAS  PubMed  Google Scholar 

  100. Mishra B, Chaurasia S. Design of novel chemotherapeutic delivery systems for colon cancer therapy based on oral polymeric nanoparticles. Ther Deliv. 2017;8:29–47.

    Article  CAS  PubMed  Google Scholar 

  101. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65:271–84.

    Article  CAS  PubMed  Google Scholar 

  102. Banerjee A, Pathak S, Subramanium VD, Dharanivasan G, Murugesan R, Verma RS. Strategies for targeted drug delivery in treatment of colon cancer: current trends and future perspectives. Drug Discov Today. 2017;22:1224–32.

    Article  CAS  PubMed  Google Scholar 

  103. Gaspar MM, Radomska A, Gobbo OL, Bakowsky U, Radomski MW, Ehrhardt C. Targeted delivery of transferrin-conjugated liposomes to an orthotopic model of lung cancer in nude rats. J Aerosol Med Pulm Drug Deliv. 2012;25:310–8.

    Article  CAS  PubMed  Google Scholar 

  104. Song H, Su C, Cui W, Zhu B, Liu L, Chen Z, et al. Folic acid-chitosan conjugated nanoparticles for improving tumor-targeted drug delivery. Biomed Res Int. 2013;2013:1–6.

    Google Scholar 

  105. Sharma M, Malik R, Verma A, Dwivedi P, Banoth GS, Pandey N, et al. Folic acid conjugated guar gum nanoparticles for targeting methotrexate to colon cancer. J Biomed Nanotechnol. 2013;9:96–106.

    Article  CAS  PubMed  Google Scholar 

  106. Santos-Rebelo A, Kumar P, Pillay V, Choonara YE, Eleutério C, Figueira M, et al. Development and mechanistic insight into the enhanced cytotoxic potential of parvifloron D albumin nanoparticles in EGFR-overexpressing pancreatic cancer cells. Cancers (Basel). 2019;11:1733.

    Article  CAS  Google Scholar 

  107. Elechalawar CK, Sridharan K, Pal A, Ahmed MT, Yousuf M, Adhikari SS, et al. Cationic folate-mediated liposomal delivery of bis-arylidene oxindole induces efficient melanoma tumor regression. Biomater Sci. 2017;5:1898–909.

    Article  CAS  PubMed  Google Scholar 

  108. Fernandez-Fernandez A, Manchanda R, McGoron AJ. Theranostic applications of nanomaterials in cancer: drug delivery, image-guided therapy, and multifunctional platforms. Appl Biochem Biotechnol. 2011;165:1628–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Bulbake U, Doppalapudi S, Kommineni N, Khan W. Liposomal formulations in clinical use: an updated review. Pharmaceutics. 2017;9:12.

    Article  PubMed Central  Google Scholar 

  110. Lamichhane N, Udayakumar T, D’Souza W, Simone C II, Raghavan S, Polf J, et al. Liposomes: clinical applications and potential for image-guided drug delivery. Molecules. 2018;23:288.

    Article  PubMed Central  Google Scholar 

  111. Kennedy PJ, Sousa F, Ferreira D, Pereira C, Nestor M, Oliveira C, et al. Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6. Acta Biomater. 2018;81:208–18.

    Article  CAS  PubMed  Google Scholar 

  112. Csaba N, Caamaño P, Sánchez A, Domínguez F, Alonso MJ. PLGA: poloxamer and PLGA: poloxamine blend nanoparticles: new carriers for gene delivery. Biomacromol. 2005;6:271–8.

    Article  CAS  Google Scholar 

  113. Cadete A, Alonso MJ. Targeting cancer with hyaluronic acid-based nanocarriers: recent advances and translational perspectives. Nanomedicine. 2016;11:2341–57.

    Article  CAS  PubMed  Google Scholar 

  114. Cruz MEM, Simões SI, Corvo ML, Martins MBF, Gaspar MM. Formulation of NPDDS for macromolecules. In: Pathak Y, Thassu D, editors. Drug Deliv Nanoparticles Formul Charact. New York, USA: Informa Healthcare; 2009. p. 35–49.

    Google Scholar 

  115. Yang C, Merlin D. Lipid-based drug delivery nanoplatforms for colorectal cancer therapy. Nanomaterials. 2020;10:1424.

    Article  CAS  PubMed Central  Google Scholar 

  116. Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015;10:975–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Perrie Y, Ramsay E. Nanomedicines: exploring the past, present and future. Drug Discov World. 2017;18:17–22.

    Google Scholar 

  118. Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303:1818–22.

    Article  CAS  PubMed  Google Scholar 

  119. Gabizon AA. Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet. Clin Cancer Res. 2001;7:223–5.

    CAS  PubMed  Google Scholar 

  120. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65:36–48.

    Article  CAS  PubMed  Google Scholar 

  121. Deshpande S, Sharma S, Koul V, Singh N. Core-shell nanoparticles as an efficient, sustained, and triggered drug-delivery system. ACS Omega. 2017;2:6455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Lila ASA, Ishida T. Liposomal delivery systems: design optimization and current applications. Biol Pharm Bull. 2017;40:1–10.

    Article  PubMed  Google Scholar 

  123. Simões S, Nuno Moreira J, Fonseca C, Düzgüneş Pedroso N, De Lima MC. On the formulation of pH-sensitive liposomes with long circulation times. Adv Drug Deliv Rev. 2004;56:947–65.

    Article  PubMed  Google Scholar 

  124. Fan Y, Chen C, Huang Y, Zhang F, Lin G. Study of the pH-sensitive mechanism of tumor-targeting liposomes. Colloids Surfaces B Biointerfaces. 2017;151:19–25.

    Article  CAS  PubMed  Google Scholar 

  125. Kamps J, Koning G, Velinova M, Morselt H, Wilkens M, Gorter A, et al. Uptake of long-circulating immunoliposomes, directed against colon adenocarcinoma cells, by liver metastases of colon cancer. J Drug Target. 2000;8:235–45.

    Article  CAS  PubMed  Google Scholar 

  126. Zalba S, Contreras AM, Haeri A, ten Hagen TLM, Navarro I, Koning G, et al. Cetuximab-oxaliplatin-liposomes for epidermal growth factor receptor targeted chemotherapy of colorectal cancer. J Control Release. 2015;210:26–38.

    Article  CAS  PubMed  Google Scholar 

  127. Zhang B, Wang T, Yang S, Xiao Y, Song Y, Zhang N, et al. Development and evaluation of oxaliplatin and irinotecan co-loaded liposomes for enhanced colorectal cancer therapy. J Control Release. 2016;238:10–21.

    Article  CAS  PubMed  Google Scholar 

  128. Bansal D, Gulbake A, Tiwari J, Jain SK. Development of liposomes entrapped in alginate beads for the treatment of colorectal cancer. Int J Biol Macromol. 2016;82:687–95.

    Article  CAS  PubMed  Google Scholar 

  129. Stathopoulos GP, Boulikas T. Lipoplatin formulation review article. J Drug Deliv. 2012;2012:1–10.

    Article  Google Scholar 

  130. Jehn CF, Boulikas T, Kourvetaris A, Possinger K, Lüftner D. Pharmacokinetics of liposomal cisplatin (lipoplatin) in combination with 5-FU in patients with advanced head and neck cancer: first results of a phase III study. Anticancer Res. 2007;27:471–5.

    CAS  PubMed  Google Scholar 

  131. Kosmas C, Angel J, Athanasiou A, Rapti A, Karanikas C, Lambaki S, et al. 9088 Phase III study of lipoplatin plus gemcitabine versus cisplatin plus gemcitabine in advanced NSCLC; interim analysis. Eur J Cancer Suppl. 2009;7:531.

    Article  Google Scholar 

  132. Dragovich T, Mendelson D, Kurtin S, Richardson K, Von Hoff D, Hoos A. A phase 2 trial of the liposomal DACH platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer. Cancer Chemother Pharmacol. 2006;58:759–64.

    Article  CAS  PubMed  Google Scholar 

  133. Hang Z, Cooper MA, Ziora ZM. Platinum-based anticancer drugs encapsulated liposome and polymeric micelle formulation in clinical trials. Biochem Compd. 2016;4:1.

    Article  Google Scholar 

  134. Seetharamu N, Kim E, Hochster H, Martin F, Muggia F. Phase II study of liposomal cisplatin (SPI-77) in platinum-sensitive recurrences of ovarian cancer. Anticancer Res. 2010;30:541–6.

    CAS  PubMed  Google Scholar 

  135. Kim ES, Lu C, Khuri FR, Tonda M, Glisson BS, Liu D, et al. A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer. Lung Cancer. 2001;34:427–32.

    Article  CAS  PubMed  Google Scholar 

  136. de Jonge MJA, Slingerland M, Loos WJ, Wiemer EAC, Burger H, Mathijssen RHJ, et al. Early cessation of the clinical development of LiPlaCis, a liposomal cisplatin formulation. Eur J Cancer. 2010;46:3016–21.

    Article  PubMed  Google Scholar 

  137. U.S. National Health Institute. Phase I/II Study to evaluate the safety and tolerability of LiPlaCis in patients with advanced or refractory tumours (LiPlaCis) [Internet]. 2019 [cited 2020 Sep 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT01861496.

  138. Stathopoulos GP, Boulikas T, Kourvetaris A, Stathopoulos J. Liposomal oxaliplatin in the treatment of advanced cancer: a phase I study. Anticancer Res. 2006;26:1489–93.

    CAS  PubMed  Google Scholar 

  139. Geszke-Moritz M, Moritz M. Solid lipid nanoparticles as attractive drug vehicles: composition, properties and therapeutic strategies. Mater Sci Eng C. 2016;68:982–94.

    Article  CAS  Google Scholar 

  140. Mei L, Zhang Z, Zhao L, Huang L, Yang XL, Tang J, et al. Pharmaceutical nanotechnology for oral delivery of anticancer drugs. Adv Drug Deliv Rev. 2013;65:880–90.

    Article  CAS  PubMed  Google Scholar 

  141. Muller RH, Shegokar R, Keck CM. 20 years of lipid nanoparticles (SLN & NLC): present state of development & industrial applications. Curr Drug Discov Technol. 2011;8:207–27.

  142. Gaspar DP, Gaspar MM, Eleutério CV, Grenha A, Blanco M, Gonçalves LMD, et al. Microencapsulated solid lipid nanoparticles as a hybrid platform for pulmonary antibiotic delivery. Mol Pharm. 2017;14:2977–90.

    Article  CAS  PubMed  Google Scholar 

  143. Madan J, Pandey RS, Jain V, Katare OP, Chandra R, Katyal A. Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve biological half-life, brain delivery and efficacy in glioblastoma cells. Nanomed Nanotechnol, Biol Med. 2013;9:492–503.

    Article  CAS  Google Scholar 

  144. Wissing SA, Kayser O, Müller RH. Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev. 2004;56:1257–72.

    Article  CAS  PubMed  Google Scholar 

  145. Tummala S, Gowthamarajan K, Satish Kumar M, Praveen T, Yamjala K, Tripuraneni NS, et al. Formulation and optimization of oxaliplatin immuno-nanoparticles using Box-Behnken design and cytotoxicity assessment for synergistic and receptor-mediated targeting in the treatment of colorectal cancer. Artif Cells, Nanomedicine, Biotechnol. 2016;44:1835–50.

    Article  CAS  Google Scholar 

  146. Guo J, Yu Z, Das M, Huang L. Nano codelivery of oxaliplatin and folinic acid achieves synergistic chemo-immunotherapy with 5-fluorouracil for colorectal cancer and liver metastasis. ACS Nano. 2020;14:5075–89.

    Article  CAS  PubMed  Google Scholar 

  147. Kotelevets L, Chastre E, Caron J, Mougin J, Bastian G, Pineau A, et al. A squalene-based nanomedicine for oral treatment of colon cancer. Cancer Res. 2017;77:2964–75.

    Article  CAS  PubMed  Google Scholar 

  148. George A, Shah PA, Shrivastav PS. Natural biodegradable polymers based nano-formulations for drug delivery: a review. Int J Pharm. 2019;561:244–64.

    Article  CAS  PubMed  Google Scholar 

  149. Ahlawat J, Henriquez G, Narayan M. Enhancing the delivery of chemotherapeutics: role of biodegradable polymeric nanoparticles. Molecules. 2018;23:1–20.

    Article  Google Scholar 

  150. Nowotnik DP. AP5346 (ProLindacTM), A DACH platinum polymer conjugate in phase II trials against ovarian cancer. Curr Bioact Compd. 2011;7:21–6.

    Article  CAS  Google Scholar 

  151. Mochida Y, Cabral H, Kataoka K. Polymeric micelles for targeted tumor therapy of platinum anticancer drugs. Expert Opin Drug Deliv. 2017;14:1423–38.

    Article  CAS  PubMed  Google Scholar 

  152. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012;161:505–22.

    Article  CAS  PubMed  Google Scholar 

  153. Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011;63:170–83.

    Article  CAS  PubMed  Google Scholar 

  154. Mirakabad FST, Nejati-Koshki K, Akbarzadeh A, Yamchi MR, Milani M, Zarghami N, et al. PLGA-based nanoparticles as cancer drug delivery systems. Asian Pacific J Cancer Prev. 2014;15:517–35.

    Article  Google Scholar 

  155. Matoba T, Egashira K. Nanoparticle-mediated drug delivery system for cardiovascular disease. Int Heart J. 2014;55:281–6.

    Article  CAS  PubMed  Google Scholar 

  156. Chaudhary Z, Ahmed N, Rehman AU, Khan GM. Lipid polymer hybrid carrier systems for cancer targeting: A review. Int J Polym Mater Polym Biomater. 2018;67:86–100.

    Article  CAS  Google Scholar 

  157. Sousa AR, Oliveira MJ, Sarmento B. Impact of CEA-targeting nanoparticles for drug delivery in colorectal cancer. J Pharmacol Exp Ther. 2019;370:657–70.

    Article  CAS  PubMed  Google Scholar 

  158. Mattheolabakis G, Taoufik E, Haralambous S, Roberts ML, Avgoustakis K. In vivo investigation of tolerance and antitumor activity of cisplatin-loaded PLGA-mPEG nanoparticles. Eur J Pharm Biopharm. 2009;71:190–5.

    Article  CAS  PubMed  Google Scholar 

  159. de S. L. Oliveira ALC, de Araújo Júnior RF, de Carvalho TG, Chan AB, Schomann T, Tamburini F, et al. Effect of oxaliplatin-loaded poly (d,l-lactide-co-glycolic acid) (PLGA) nanoparticles combined with retinoic acid and cholesterol on apoptosis, drug resistance, and metastasis factors of colorectal cancer. Pharmaceutics. 2020;12:193.

  160. Margiotta N, Marzano C, Gandin V, Osella D, Ravera M, Gabano E, et al. Revisiting [PtCl2(cis -1,4-DACH)]: an underestimated antitumor drug with potential application to the treatment of oxaliplatin-refractory colorectal cancer. J Med Chem. 2012;55:7182–92.

    Article  CAS  PubMed  Google Scholar 

  161. Margiotta N, Savino S, Denora N, Marzano C, Laquintana V, Cutrignelli A, et al. Encapsulation of lipophilic kiteplatin Pt(IV) prodrugs in PLGA-PEG micelles. Dalt Trans. 2016;45:13070–81.

    Article  CAS  Google Scholar 

  162. de Moraes PD, Pessine FBT. Formulation of functionalized PLGA nanoparticles with folic acid-conjugated chitosan for carboplatin encapsulation. Eur Polym J. 2018;108:311–21.

    Article  Google Scholar 

  163. Hackl CM, Schoenhacker-Alte B, Klose MHM, Henke H, Legina MS, Jakupec MA, et al. Synthesis and in vivo anticancer evaluation of poly(organo)phosphazene-based metallodrug conjugates. Dalt Trans. 2017;46:12114–24.

    Article  CAS  Google Scholar 

  164. Izadi Z, Divsalar A, Saboury AA, Sawyer L. β-Lactoglobulin-pectin nanoparticle-based oral drug delivery system for potential treatment of colon cancer. Chem Biol Drug Des. 2016;88:209–16.

    Article  CAS  PubMed  Google Scholar 

  165. Jain A, Jain SK, Ganesh N, Barve J, Beg AM. Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer. Nanomed Nanotechnol, Biol Med. 2010;6:179–90.

    Article  CAS  Google Scholar 

  166. Saber MM, Al-mahallawi AM, Nassar NN, Stork B, Shouman SA. Targeting colorectal cancer cell metabolism through development of cisplatin and metformin nano-cubosomes. BMC Cancer. 2018;18:822.

    Article  PubMed  PubMed Central  Google Scholar 

  167. Nishiyama N, Okazaki S, Cabral H, Miyamoto M, Kato Y, Sugiyama Y, et al. Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice. Cancer Res. 2003;63:8977–83.

    CAS  PubMed  Google Scholar 

  168. Wu H, Cabral H, Toh K, Mi P, Chen Y-C, Matsumoto Y, et al. Polymeric micelles loaded with platinum anticancer drugs target preangiogenic micrometastatic niches associated with inflammation. J Control Release. 2014;189:1–10.

    Article  CAS  PubMed  Google Scholar 

  169. Pöthig A, Casini A. Recent developments of supramolecular metal-based structures for applications in cancer therapy and imaging. Theranostics. 2019;9:3150–69.

    Article  PubMed  PubMed Central  Google Scholar 

  170. Woods B, Wenzel MN, Williams T, Thomas SR, Jenkins RL, Casini A. Exo-functionalized metallacages as host-guest systems for the anticancer drug cisplatin. Front Chem. 2019;7:68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Han J, Räder AFB, Reichart F, Aikman B, Wenzel MN, Woods B, et al. Bioconjugation of supramolecular metallacages to integrin ligands for targeted delivery of cisplatin. Bioconjug Chem. 2018;29:3856–65.

    Article  CAS  PubMed  Google Scholar 

  172. Meier-Menches SM, Zappe K, Bileck A, Kreutz D, Tahir A, Cichna-Markl M, et al. Time-dependent shotgun proteomics revealed distinct effects of an organoruthenium prodrug and its activation product on colon carcinoma cells. Metallomics. 2019;11:118–27.

    Article  CAS  PubMed  Google Scholar 

  173. Steel TR, Hartinger CG. Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs. Metallomics. 2020;12:1627–36.

    Article  CAS  PubMed  Google Scholar 

  174. Anthony EJ, Bolitho EM, Bridgewater HE, Carter OWL, Donnelly JM, Imberti C, et al. Metallodrugs are unique: opportunities and challenges of discovery and development. Chem Sci. 2020;11:12888–917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Wenzel M, Casini A. Mass spectrometry as a powerful tool to study therapeutic metallodrugs speciation mechanisms: current frontiers and perspectives. Coord Chem Rev. 2017;352:432–60.

    Article  CAS  Google Scholar 

  176. Crommelin DJA, van Hoogevest P, Storm G. The role of liposomes in clinical nanomedicine development. What now? Now what? J Control Release. 2020;318:256–63.

    Article  CAS  PubMed  Google Scholar 

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Funding

Fundação para a Ciência e a Tecnologia (FCT) for financial support through Projects UIDB/04138/2020, UIDP/04138/2020 and PTDC/MED-QUI/31721/2017, as well as for the PhD fellowship SFRH/BD/117586/2016.

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  1. Pedro Farinha and Jacinta O. Pinho have contributed equally to this work

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  1. Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal

    Pedro Farinha

  2. Faculty of Pharmacy, Research Institute for Medicines, iMed.ULisboa, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal

    Jacinta O. Pinho, Mariana Matias & M. Manuela Gaspar

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All authors whose names appear on the submission made substantial contributions to the article. Pedro Farinha—writing and original draft preparation; Pedro Farinha, Jacinta O. Pinho, Mariana Matias and Maria Manuela Gaspar—writing, editing, and critical revision of intellectual content; Pedro Farinha, Jacinta O. Pinho, Mariana Matias, and Maria Manuela Gaspar—conceptualization and supervision. All authors read and approved the final manuscript.

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Farinha, P., Pinho, J.O., Matias, M. et al. Nanomedicines in the treatment of colon cancer: a focus on metallodrugs. Drug Deliv. and Transl. Res. 12, 49–66 (2022). https://doi.org/10.1007/s13346-021-00916-7

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