NANOTAŞIYICILARIN KANSER HÜCRELERİNE AKTİF VE PASİF OLARAK HEDEFLENMESİNDE KULLANILAN YÖNTEMLER

Öz

Nanoteknolojideki gelişmelerle beraber her geçen gün artan kullanım alanı ve kolaylığı ile nanomalzeme temelli ilaç taşıma sistemleri; ilaç moleküllerinin tümör dokusuna hedeflenmesi, tümör hücresindeki çoklu ilaç direncinin kırılması ve doza bağlı azalmış teröpatik etkinin iyileştirilmesinde potansiyel güçlü özelliklere sahiptir. Son yıllarda, birçok kanser türünü hedefleyen antikanser tedavi stratejilerinde, nanoteknolojiye dayalı yeni metotlar ve yaklaşımların geliştirilmesiyle nanomalzemelere karşı ilgi artmaktadır. Nanoteknolojideki gelişmelerin hızlı bir şekilde ilerlemesiyle birlikte nanomalzemelerin kanser terapötiklerine entegrasyonu ve kanser hücrelerinin yüzeylerinde bulunan belirteçlere spesifik hedeflenmesi kanser tedavisinde devrim niteliğinde iyileşmeler sağlamıştır. Nano taşıyıcı sistemlerinde ilaç yüklemesi sayesinde vücutta artan ilaç yüklenmesi nedeniyle oluşan toksisitenin azalmasını sağlayan iyileştirilmiş ilaç yarı ömür, kontrollü ve seçici ilaç salınımı için bileşenlerin boyutları, morfolojileri ve yüzey kimyaları çeşitli yöntemlerle değiştirilerek ilaç taşıma sistemleri yeniden tasarlanabilmektedir. Böylece özel yapım nanomateryaller, kanser hücrelerini öngörülebilir bir şekilde hedefleyerek yüklü ilaçları etkili bir şekilde kanser hücresine iletebilir. Şimdiye kadar, kanser tedavisinde nano ölçekli boyutları ve çok yönlü fizikokimyasal özellikleri nedeniyle geleneksel formülasyonlara göre hazırlanmış daha üstün farmakokinetik ve farmakodinamik profillere sahip akıllı ilaç salınım sistemlerinde kullanılması için polimerik nanomateryaller, metalik nanopartiküller, karbon bazlı materyaller, lipozomlar ve dendrimerler üretilmiştir. Bu derlemede, ilaç taşıma sistemlerinin oluşturulmasında temel olarak kullanılan nanopartiküller, miseller, karbon nanotüpler, dendrimerler, kuantum noktaları ve lipozomlar dahil olmak üzere çeşitli ilaç salınım sistemlerinin fizikokimyasal, farmakokinetik ve farmakodinamik özelliklerinin avantajları ve dezavantajlarının ortaya konması amaçlanmıştır. Bunun yanı sıra pasif ve aktif taşıma olmak üzere iki farklı ilaç taşıma yönteminin kanser tedavisindeki uygulama alanları tartışılarak nanotaşıyıcı sistemlerin gelecekteki klinik çalışmalarda kullanımları açısından konuyla ilgilenenler için bir perspektif oluşturmaktadır.

Anahtar Kelimeler

• Nanoteknoloji
• Kemoterapi
• İlaç dağıtım sistemleri.

METHODS USED IN ACTIVE AND PASSIVE TARGETING OF NANO CARRIERS TO CANCER CELLS

Öz

With the developments in nanotechnology, nanomaterial-based drug delivery systems with their increasing and ease of use, have powerful properties in targeting drug molecules to tumor tissue, breaking multi-drug resistance in tumor cells and improving the dose-dependent reduced therapeutic effect. In recent years, interest in nanomaterials has been increasing with the development of new methods and approaches based on nanotechnology in anticancer treatment strategies targeting many types of cancer. With the rapid progress of developments in nanotechnology, the integration of nanomaterials into cancer therapeutics and the specific targeting of markers on the surfaces of cancer cells have provided revolutionary improvements in cancer treatment. Due to drug loading in nanocarrier systems, drug delivery systems can be redesigned by changing the sizes, morphologies and surface chemistry of the components with various methods for improved drug half-life, controlled and selective drug release, which reduces the toxicity caused by increased drug loading in the body. Thus, custom-made nanomaterials can predictably target cancer cells, effectively delivering the loaded drugs to the cancer cell. So far, polymeric nanomaterials, metallic nanoparticles, carbon-based materials, liposomes and dendrimers have been produced for use in smart drug delivery systems with superior pharmacokinetic and pharmacodynamic profiles prepared compared to conventional formulations due to their nanoscale dimensions and versatile physicochemical properties in cancer therapy. In this review, it is aimed to reveal the advantages and disadvantages of the physicochemical, pharmacokinetic and pharmacodynamic properties of various drug delivery systems, including nanoparticles, micelles, carbon nanotubes, dendrimers, quantum dots and liposomes, which are used as the basis for the creation of drug delivery systems. In addition, the application areas of two different drug transport methods, passive and active transport, in cancer treatment are discussed, and it creates a perspective for those interested in the subject in terms of the use of nanocarrier systems in future clinical studies.

Anahtar Kelimeler

• Nanotechnology
• Chemotherapy
• Drug delivery systems.

Kaynakça

1. 1. Sarkar FH, Banerjee S, Li Y. Pancreatic cancer: Pathogenesis, prevention and treatment. Toxicol Appl Pharmacol. 2007;224:326–36.
2. 2. You W, Henneberg M. Cancer incidence increasing globally: The role of relaxed natural selection. Evol Appl. 2018;11:140–52.
3. 3. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008;60:1615–26.
4. 4. Wiradharma N, Zhang Y, Venkataraman S, Hedrick JL, Yang YY. Self-assembled polymer nanostructures for delivery of anticancer therapeutics. Nano Today. 2009;4:302–17.
5. 5. Pulkkinen M, Pikkarainen J, Wirth T, et al. Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology: Formulation development and in vitro anticancer activity. Eur J Pharm Biopharm. 2008;70:66–74.
6. 6. Navya PN, Kaphle A, Srinivas SP, Bhargava SK, Rotello VM, Daima HK. Current trends and challenges in cancer management and therapy using designer nanomaterials. Nano Converg. 2019;6:1–30.
7. 7. Navya PN, Daima HK. Rational engineering of physicochemical properties of nanomaterials for biomedical applications with nanotoxicological perspectives. Nano Converg. 2016;3:1.
8. 8. Mangadlao JD, Wang X, McCleese C, et al. Prostate-Specific Membrane Antigen Targeted Gold Nanoparticles for Theranostics of Prostate Cancer. ACS Nano. 2018;12:3714–25.

9. 9. Banu H, Renuka N, Faheem SM, et al. Gold and Silver Nanoparticles Biomimetically Synthesized Using Date Palm Pollen Extract-Induce Apoptosis and Regulate p53 and Bcl-2 Expression in Human Breast Adenocarcinoma Cells. Biol Trace Elem Res. 2018;186:122–34.
10. 10. Ahmed MSU, Salam A Bin, Yates C, et al. Double-receptor-targeting multifunctional iron oxide nanoparticles drug delivery system for the treatment and imaging of prostate cancer. Int J Nanomedicine. 2017;12:6973–84.
11. 11. Navya PN, Kaphle A, Daima HK. Nanomedicine in sensing, delivery, imaging and tissue engineering: Advances, opportunities and challenges. SPR Nanosci. 2019;5:30–56.
12. 12. Kumar M, Sharma G, Misra C, et al. N-desmethyl tamoxifen and quercetin-loaded multiwalled CNTs: A synergistic approach to overcome MDR in cancer cells. Mater Sci Eng C. 2018;89:274–82.
13. 13. Mehra NK, Mishra V, Jain NK. A review of ligand tethered surface engineered carbon nanotubes. Biomaterials. 2014;35:1267–83.
14. 14. Karki N, Tiwari H, Pal M, et al. Functionalized graphene oxides for drug loading, release and delivery of poorly water soluble anticancer drug: A comparative study. Colloids Surfaces B Biointerfaces. 2018;169:265– 72.
15. 15. Wei Z, Yin XT, Cai Y, et al. Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma. Int J Nanomedicine. 2018;13:1505–24.
16. 16. Cai W, Chen X. Nanoplatforms for targeted molecular imaging in living subjects. Small. 2007;3:1840–54.
17. 17. Kim KY. Nanotechnology platforms and physiological challenges for cancer therapeutics. Nanomedicine Nanotechnology, Biol Med. 2007;3:103–10.
18. 18. Wang B, Qiao W, Wang Y, et al. Cancer therapy based on nanomaterials and nanocarrier systems. J Nanomater. 2010;79630.
19. 19. Manzano M, Vallet-Regí M. Mesoporous silica nanoparticles in nanomedicine applications. J Mater Sci Mater Med. 2018;29:65.
20. 20. Daima HK, Shankar S, Anderson A, et al. Complexation of plasmid DNA and poly(ethylene oxide)/poly(propylene oxide) polymers for safe gene delivery. Environ Chem Lett. 2018;16:1457–62.
21. 21. Gubernator J. Active methods of drug loading into liposomes: Recent strategies for stable drug entrapment and increased in vivo activity. Expert Opin Drug Deliv. 2011;8:565–80.
22. 22. Sercombe L, Veerati T, Moheimani F, et al. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286.
23. 23. Pattni BS, Chupin V V., Torchilin VP. New Developments in Liposomal Drug Delivery. Chem Rev. 2015;115:10938–66.
24. 24. Masood F. Polymeric nanoparticles for targeted drug delivery system for cancer therapy. Mater Sci Eng C. 2016;60:569–78.
25. 25. Maghsoudnia N, Eftekhari RB, Sohi AN, et al. Application of nano-based systems for drug delivery and targeting: a review. J Nanoparticle Res. 2020;22:1–41.
26. 26. Yang W, Cheng Y, Xu T, Wang X, Wen L ping. Targeting cancer cells with biotin-dendrimer conjugates. Eur J Med Chem. 2009;44:862–8.
27. 27. Mignani S, Rodrigues J, Tomas H, et al. Dendrimers in combination with natural products and analogues as anti-cancer agents. Chem Soc Rev. 2018;47:514–32.
28. 28. Li LB, Tan YB. Preparation and properties of mixed micelles made of Pluronic polymer and PEG-PE. J Colloid Interface Sci 2008;317:326–31.
29. 29. Mikhail AS, Allen C. Block copolymer micelles for delivery of cancer therapy: Transport at the whole body, tissue and cellular levels. J Control Release. 2009;138:214–23.
30. 30. Chitgupi U, Qin Y, Lovell JF. Targeted nanomaterials for phototherapy. Nanotheranostics. 2017;1:38–58.
31. 31. Du W, Elemento O. Cancer systems biology: Embracing complexity to develop better anticancer therapeutic strategies. Oncogene. 2015;34:3215–25.
32. 32. Bugaj AM. Targeted photodynamic therapy - A promising strategy of tumor treatment. Photochem Photobiol Sci. 2011;10:1097–109.
33. 33. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65:71–9.
34. 34. Jain RK, Stylianopoulos T. Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol. 2010;7:653–64.
35. 35. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014;66:2–25.
36. 36. Rosenblum D, Joshi N, Tao W, Karp JM, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun. 2018;9:1–12.
37. 37. Krasnici S, Werner A, Eichhorn ME, et al. Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels. Int J Cancer. 2003;105:561–7.
38. 38. Ichikawa K, Hikita T, Maeda N, et al. PEGylation of liposome decreases the susceptibility of liposomal drug in cancer photodynamic therapy. Biol Pharm Bull. 2004;27:443–4.
39. 39. Pires P, Simões S, Nir S, et al. Interaction of cationic liposomes and their DNA complexes with monocytic leukemia cells. Biochim Biophys Acta - Biomembr. 1999;1418:71–84.
40. 40. Thurston G, McLean JW, Rizen M, et al. Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice. J Clin Invest. 1998;101:1401–13.
41. 41. Synatschke C V., Nomoto T, Cabral H, et al. Multicompartment micelles with adjustable poly(ethylene glycol) shell for efficient in vivo photodynamic therapy. ACS Nano. 2014;8:1161–72.
42. 42. Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: Progress, challenges and opportunities. Nat Rev Cancer. 2017;17:20–37.
43. 43. Lancet JE, Uy GL, Cortes JE, et al. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016;34:7000.
44. 44. Chauhan VP, Jain RK. Strategies for advancing cancer nanomedicine. Nat Mater. 2013;12:958–62.
45. 45. Ernsting MJ, Murakami M, Roy A, Li SD. Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J Control Release. 2013;172:782–94.
46. 46. Peer D, Karp JM, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2:751–60.
47. 47. Varki A. Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins. Nature. 2007;446:1023–9.
48. 48. Verma A, Stellacci F. Effect of surface properties on nanoparticle-cell interactions. Small. 2010;6:12–21.
49. 49. Mout R, Moyano DF, Rana S, Rotello VM. Surface functionalization of nanoparticles for nanomedicine. Chem Soc Rev. 2012;41:2539–44.
50. 50. Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. 2018;12:3–20.
51. 51. Ohno SI, Takanashi M, Sudo K, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microrna to breast cancer cells. Mol Ther. 2013;21:185–91.
52. 52. Gao J, Feng SS, Guo Y. Antibody engineering promotes nanomedicine for cancer treatment. Nanomedicine. 2010;5:1141–5.
53. 53. Choi CHJ, Alabi CA, Webster P, Davis ME. Mechanism of active targeting in solid tumors with transferrin- containing gold nanoparticles. Proc Natl Acad Sci USA. 2010;107:1235–40.
54. 54. Yao Y, Zhou Y, Liu L, et al. Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. Front Mol Biosci. 2020;7:193.
55. 55. Liu J, Li Y, Chen S, et al. Biomedical Application of Reactive Oxygen Species–Responsive Nanocarriers in Cancer, Inflammation, and Neurodegenerative Diseases. Front Chem. 2020;8:838.
56. 56. Monteiro PF, Travanut A, Conte C, Alexander C. Reduction-responsive polymers for drug delivery in cancer therapy—Is there anything new to discover? Wiley Interdiscip Rev Nanomedicine Nanobiotechnology. 2021;13:e1678.
57. 57. Song CC, Du FS, Li ZC. Oxidation-responsive polymers for biomedical applications. J Mater Chem B. 2014;2:3413–26.
58. 58. Kato Y, Ozawa S, Miyamoto C, et al. Acidic extracellular microenvironment and cancer. Cancer Cell Int. 2013;13:1–8.
59. 59. Kumar CSSR, Mohammad F. Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Adv Drug Deliv Rev. 2011;63:789–808.
60. 60. Agostini A, Sancenón F, Martínez-Máñez R, et al. A photoactivated molecular gate. Chem - A Eur J. 2012;18:12218–21.
61. 61. Lee SF, Zhu XM, Wang YXJ, et al. Ultrasound, pH, and magnetically responsive crown-ether-coated core/shell nanoparticles as drug encapsulation and release systems. ACS Appl Mater Interfaces. 2013;5:1566–74.
62. 62. Jin Z, Güven G, Bocharova V, Halámek J, et al. Electrochemically controlled drug-mimicking protein release from iron-alginate thin-films associated with an electrode. ACS Appl Mater Interfaces. 2012;4:466–75.
63. 63. Yu M, Park J, Jon S. Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics. 2012;2:3–44.
64. 64. Juan A, Cimas FJ, Bravo I, A. Pandiella, A. Ocaña, C. Alonso-Moreno. An Overview of Antibody Conjugated Polymeric Nanoparticles for Breast Cancer Therapy. Pharmaceutics. 2020;12:1–20.
65. 65. Dang MN, Hoover EC, Scully MA, Sterin EH, Day ES. Antibody Nanocarriers for Cancer Management. Curr Opin Biomed Eng. 2021;19.
66. 66. Jiang H, Pan V, Vivek S, et al. Programmable DNA Hydrogels Assembled from Multidomain DNA Strands. Chembiochem. 2016;17:1156–62.
67. 67. Ashrafuzzaman M. Aptamers as both drugs and drug-carriers. Biomed Res Int. 2014;2014: 697923
68. 68. Awwad S, Angkawinitwong U. Overview of Antibody Drug Delivery. Pharmaceutics. 2018;10(3):83.
69. 69. Morales-Cruz, M, Delgado, Y, Castillo B, et al. Smart Targeting To Improve Cancer Therapeutics. Drug Design, Development and Therapy. 2019;13: 3753.
70. 70. Berillo D, Yeskendir A, Zharkinbekov Z, Raziyeva K, & Saparov A. Peptide-Based Drug Delivery Systems. Medicina. 2021;57(11): 1209.
71. 71. Borandeh S, van Bochove B, Teotia A, & Seppäläm J. Polymeric drug delivery systems by additive manufacturing. Advanced Drug Delivery Reviews. 2021;6(173):349–373.
72. 72. Campuzano S, Gamella M, Serafín V, et al. Magnetic Janus Particles for Static and Dynamic (Bio)Sensing. Magnetochemistry. 2019;5(3): 47.
73. 73. Pan P, Svirskis D, Rees SWP, et al. Photosensitive drug delivery systems for cancer therapy: Mechanisms and applications. Journal of Controlled Release. 2021;10:(338): 446–61.
74. 74. Daima HK, Selvakannan PR, Kandjani AE, et al. Synergistic influence of polyoxometalate surface corona towards enhancing the antibacterial performance of tyrosine-capped Ag nanoparticles. Nanoscale. 2014;6:758–65.
75. 75. Ruozi B, Belletti D, Sharma HS, et al. PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury. Mol Neurobiol. 2015;52:899–912.
76. 76. Ma S, Zhou J, Zhang Y, et al. Highly Stable Fluorinated Nanocarriers with iRGD for Overcoming the Stability Dilemma and Enhancing Tumor Penetration in an Orthotopic Breast Cancer. ACS Appl Mater Interfaces. 2016;8:28468–79.
77. 77. Wang Y, Santos A, Evdokiou A, Losic D. An overview of nanotoxicity and nanomedicine research: Principles, progress and implications for cancer therapy. J Mater Chem B. 2015;3:7153–72.
78. 78. Coradeghini R, Gioria S, García CP, et al. Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts. Toxicol Lett. 2013;217:205–16.
79. 79. Ji Z, Wang X, Zhang H, et al. Designed synthesis of CeO 2 nanorods and nanowires for studying toxicological effects of high aspect ratio nanomaterials. ACS Nano. 2012;6:5366–80.