THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS

Sadık Kağa; Didem Kesgin; Elif Kağa

doi:10.18229/kocatepetip.1676373

Araştırma Makalesi

BibTex

RIS

Kaynak Göster

THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS

Yıl 2025, Cilt: 26 Sayı: 3, 262 - 271, 16.07.2025

Sadık Kağa , Didem Kesgin , Elif Kağa

https://doi.org/10.18229/kocatepetip.1676373

Öz

OBJECTIVE: Although chemotherapy is widely used in the treatment of cancer, it suffers due to the nonspecific biodistribution and side effects of chemotherapy agents. In this study, a nano formulation that can both prevent the formation of drug resistance and increase the effectiveness of treatment was developed.
MATERIAL AND METHODS: Docetaxel (DTX) and Combretastatin A4 (CA4) loaded PEG-PLGA (Poly(ethylene glycol)-block-Poly(lactide-co-glycolide) polymeric nanoparticles were fabricated with mono and binary drug loading. The size and morphology of the nanoparticles were characterized using Transmission Electron Microscopy (TEM). The UV-Vis spectrometer determined critical Micelle Concentration (CMC) values, drug encapsulation efficiency, and drug release profiles of the mono and binary drug-loaded nanoparticles. In vitro efficiency of the DTX and CA4 loaded PEG-PLGA nanoparticles was tested using a human breast cancer cell line (MCF-7) compared to free drug formulations.
RESULTS: PEG-PLGA nanoparticles had a CMC value of 0.0126 mM. The size of the particles was measured at around 5-10 nm. They released almost all loaded content in 4 days at pH 5.5, whereas this value remained 60% at pH 7.4. DTX and CA4 loaded nanoparticles showed a lower EC50 value than the dual free drug formulation.
CONCLUSIONS: The designed nano dual drug formulation can be an alternative chemotherapy solution for cancer treatment.

Anahtar Kelimeler

Docetaxel, Combretastatin A4, Nanoparticle, Dual Therapy, Cancer

Etik Beyan

A commercially purchased cell line was used in the study. Therefore, it does not require any ethics committee approval.

Destekleyen Kurum

Afyon Kocatepe Univesity

Proje Numarası

20.FEN.BİL.10

Teşekkür

This study was supported by the Afyon Kocatepe University Scientific Research Projects Commission under grant number 20.FEN.BİL.10

Kaynakça

1. Soerjomataram I, Bray F, Wild CP, Weiderpass E, Stewart BW. World Cancer Report. Cancer research for cancer prevention. 2020.
2. Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1, 1st ed.; McGraw-Hill Education: New York, NY, USA.2017;416–19.
3. Nussbaumer S, Bonnabry P, Veuthey JL, Fleury-Souverain S. Analysis of anticancer drugs: a review. Talanta. 2011;85(5):2265-89.
4. YA L. Mechanisms of drug resistance in cancer chemotherapy. Cancer Drug Resist. 2005;14:34-48.
5. Kalyane D, Raval N, Maheshwari R, et al. Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. Mat. Sci. Eng. C. 2019;98:1252-76.
6. Cassatt DR, Winters TA, PrabhuDas M. Immune Dysfunction from Radiation Exposure. Radiat Res. 2023;200(4):389-95.
7. Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2019;2(2):141-60.
8. Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Int. J. Mol. Sci. 2020;21(9):3233.
9. Wu CP, Hsiao SH, Huang YH, et al. Sitravatinib sensitizes ABCB1-and ABCG2-overexpressing multidrug- resistant cancer cells to chemotherapeutic drugs. Cancers. 2020;12(1):195.
10. Nanayakkara AK, Follit CA, Chen G, Williams NS, Vogel PD, Wise JG. Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells. Scientific Reports. 2018;8(1):967.
11. Xu JL, Jin B, Ren ZH, et al. Chemotherapy plus erlotinib versus chemotherapy alone for treating advanced non-small cell lung cancer: a meta-analysis. PloS one. 2015;10(7):e0131278.
12. Lee JH, Nan A. Combination drug delivery approaches in metastatic breast cancer. J. Drug Deliv. 2012;2012(1):1-17.
13. Mokhtari RB, Homayouni TS, Baluch N, et al. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022-43.
14. Gong J, Shi T, Liu J, et al. Dual-drug codelivery nanosystems: An emerging approach for overcoming cancer multidrug resistance. Biomed. Pharmacother. 2023;161:114505.
15. Nakamura Y, Mochida A, Choyke PL, et al. Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer?. Bioconjugate Chem. 2016;27(10):2225-38.
16. Kim J, Cho H, Lim DK, et al. Perspectives for improving the tumor targeting of nanomedicine via the EPR effect in clinical tumors. Int. J. Mol. Sci. 2023;24(12):10082.
17. Alkaç İM, Keskin S, Çerçi B. Nanotaşiyicilarin kanser hücrelerine aktif ve pasif olarak hedeflenmesinde kullanilan yöntemler. Kocatepe Tıp Dergisi. 2024;25(3):396-406.
18. Wei X, Song M, Li W, et al. Multifunctional nanoplatforms co-delivering combinatorial dual-drug for eliminating cancer multidrug resistance. Theranostics. 2021;11(13):6334-54.
19. Zhang RX, Wong HL, Xue HY, et al. Nanomedicine of synergistic drug combinations for cancer therapy– Strategies and perspectives. J. Control. Release 2016;240:489-503.
20. Babos G, Biró E, Meiczinger M, Feczkó T. Dual drug delivery of sorafenib and doxorubicin from PLGA and PEG- PLGA polymeric nanoparticles. Polymers. 2018;10(8):895-902.
21. Karimian-Shaddel A, Dadashi H, Mashinchian M, et al. Codelivery of metformin and methotrexate with optimized chitosan nanoparticles for synergistic triple-negative breast cancer therapy in vivo. Int. J. Pharm. 2024;667:124897.
22. Elzayat EM, Sherif AY, Nasr FA, et al. Enhanced codelivery of gefitinib and azacitidine for treatment of metastatic-resistant lung cancer using biodegradable lipid nanoparticles. Materials. 2023;16(15):5364.
23. Rong J, Liu T, Yin X, et al. Co-delivery of camptothecin and MiR-145 by lipid nanoparticles for MRI-visible targeted therapy of hepatocellular carcinoma. J. Exp. Clin. Cancer Res. 2024;43(1):247.
24. Yadav PK, Saklani R, Tiwari AK, et al. Ratiometric codelivery of Paclitaxel and Baicalein loaded nanoemulsion for enhancement of breast cancer treatment. Int. J. Pharm. 2023;643:123209.
25. Imran M, Saleem S, Chaudhuri A, et al. Docetaxel: An update on its molecular mechanisms, therapeutic trajectory and nanotechnology in the treatment of breast, lung and prostate cancer. J. Drug Deliv. Sci. Technol. 2020;60:101959.
26. Griggs J, Hesketh R, Smith GA, et al. Combretastatin-A4 disrupts neovascular development in non- neoplastic tissue. Br. J. Cancer. 2001;84(6):832-5.
27. Zhang D, Liu L, Wang J, et al. Drug-loaded PEG-PLGA nanoparticles for cancer treatment. Front. Pharmacol. 2022;13:990505.
28. Sulaiman TN, Larasati D, Nugroho AK, et al. Assessment of the Effect of PLGA Co-polymers and PEG on the Formation and Characteristics of PLGA-PEG-PLGA Co-block Polymer Using Statistical Approach. Adv. Pharm. Bull. 2019;9(3):382-92.
29. Gref R, Minamitake Y, Peracchia MT, et al. Biodegradable long-circulating polymeric nanospheres. Science. 1994;263(5153):1600-3.
30. Tan CH, Huang ZJ, Huang XG. Rapid determination of surfactant critical micelle concentration in aqueous solutions using fiber-optic refractive index sensing. Anal. Biochem. 2010;401(1):144-7.
31. Elsey D, Jameson D, Raleigh B, Cooney MJ. Fluorescent measurement of microalgal neutral lipids. J. Microbiol. Methods. 2007;68(3):639-42.
32. Tajalli H, Gilani AG, Zakerhamidi MS, et al. The photophysical properties of Nile red and Nile blue in ordered anisotropic media. Dyes and Pigments. 2008;78(1):15-24.
33. Ray GB, Chakraborty I, Moulik SP. Pyrene absorption can be a convenient method for probing critical micellar concentration (cmc) and indexing micellar polarity. J. Colloid Interface Sci. 2006;294(1):248-54.
34. Kang RH, Kim NH, Kim D. A transformable and biocompatible polymer series using ring-opening polymerization of cyclic silane for more effective transdermal drug delivery. Chem. Eng. J. 2022;440:135989.
35. Nahar M, Jain NK. Preparation, characterization and evaluation of targeting potential of amphotericin B- loaded engineered PLGA nanoparticles. Pharm. Res. 2009;26:2588-98.
36. Wang Y, Chen H, Liu Y, et al. pH-sensitive pullulan-based nanoparticle carrier of methotrexate and combreta statin A4 for the combination therapy against hepatocellular carcinoma. Biomaterials. 2013;34(29):7181-90.
37. Rafiei P, Haddadi A. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile. Int. J. Nanomedicine. 2017:935-47.
38. Samkange T, D'Souza S, Obikeze K, Dube A. Influence of PEGylation on PLGA nanoparticle properties, hydrophobic drug release and interactions with human serum albumin.J. Pharm. Pharmacol. 2019;71(10):1497- 507.
39. Kaksonen M, Roux A. Mechanisms of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 2018;19(5):321.
40. Wang X, Li L, Song F. Interplay of nanoparticle properties during endocytosis. Crystals. 2021;11(7):728.
41. Digiacomo L, Renzi S, Pirrottina A, et al. PEGylation-Dependent Cell Uptake of Lipid Nanoparticles Revealed by Spatiotemporal Correlation Spectroscopy. ACS Pharmacol. Transl. Sci. 2024;7(10):3004-10.
42. Zhang Y, Sun C, Zhang Q, et al. Intranasal delivery of Paclitaxel encapsulated nanoparticles for brain injury due to Glioblastoma.J. Appl. Biomater. Funct. Mater. 2020;18:2280800020977170.
43. Redrado M, Xiao Z, Upitak K,et al. Applications of biodegradable polymers in the encapsulation of anticancer metal complexes. Adv. Funct. Mater. 2024;34(36):2401950.
44. Zaid AN, Hassan M, Jaradat N, et al. Formulation and characterization of combretastatin A4 loaded PLGA nanoparticles. Materials Research Express. 2020;6(12):1250d7.
45. Bariwal J, Kumar V, Chen H, et al. Nanoparticulate delivery of potent microtubule inhibitor for metastatic melanoma treatment. J Control Release. 2019;309:231-43.
46. Noori Koopaei M, Khoshayand MR, Mostafavi SH, et al. Docetaxel Loaded PEG-PLGA Nanoparticles: Optimized Drug Loading, In-vitro Cytotoxicity and In-vivo Antitumor Effect. Iran J Pharm Res. 2014;13(3):819-33.
47. Wu J. The enhanced permeability and retention (EPR) effect: the significance of the concept and methods to enhance its application. J. Pers. Med. 2021;11(8):771.

İNSAN MEME KANSERİ HÜCRELERİNDE DOSETAKSEL VE KOMBRETASTATİN A4 YÜKLÜ PEG-PLGA NANOPARTİKÜLLERİNİN TEDAVİ ETKİNLİĞİ

Yıl 2025, Cilt: 26 Sayı: 3, 262 - 271, 16.07.2025

Sadık Kağa , Didem Kesgin , Elif Kağa

https://doi.org/10.18229/kocatepetip.1676373

Öz

AMAÇ: Kemoterapi kanser tedavisinde yaygın olarak kullanılmasına rağmen, kemoterapi ajanlarının nonspesifik biyodağılımları ve yan etkileri nedeniyle problemler mevcuttur. Bu çalışmada, hem ilaç direncinin oluşumunu önleyebilen hem de tedavinin etkinliğini artırabilen bir nanoformülasyon geliştirilmiştir.
GEREÇ VE YÖNTEM: Docetaxel (DTX) ve Combretastatin A4 (CA4) yüklü PEG-PLGA (Poli(etilen glikol)-blok-Poli(laktid-ko-glikolid) polimerik nanopartiküller mono ve ikili ilaç yüklemesi ile üretildi. Nanopartiküllerin boyutu ve morfolojisi Transmisyon Elektron Mikroskobu (TEM) kullanılarak karakterize edildi. Tekli ve ikili ilaç yüklü nanopartiküllerin kritik misel konsantrasyonu (CMC) değerleri, ilaç kapsülleme verimliliği ve ilaç salım profilleri UV-Vis spektrometresi ile belirlendi. DTX ve CA4 yüklü PEG-PLGA nanopartiküllerinin in vitro etkinliği, serbest ilaç formülasyonlarıyla karşılaştırılarak, insan meme kanseri hücre hattında (MCF-7) test edildi.
BULGULAR: PEG-PLGA nanopartiküllerine ait CMC değeri 0,0126 mM olarak bulunmuştur. Partikül boyutları yaklaşık 5–10 nm aralığında ölçülmüştür. Nanopartiküller, pH 5,5 koşullarında, 4 gün içinde neredeyse tüm yüklü içeriği serbest bırakırken, pH 7,4 ortamında bu oran %60 seviyesinde kalmıştır. DTX ve CA4 yüklü nanopartiküller, ikili serbest ilaç formülasyonuna kıyasla daha düşük bir EC50 değeri sergilemiştir.
SONUÇ: Tasarlanan ikili nano ilaç formülasyonu, kanser tedavisi için alternatif bir kemoterapi çözümü olabilir.

Anahtar Kelimeler

Docetaksel, Kombretastatin A4, Nanopartikül, İkili terapi, Kanser.

Etik Beyan

Çalışmada ticari olarak satın alınan bir hücre hattı kullanıldı. Bu nedenle herhangi bir etik kurul onayına ihtiyaç duyulmamaktadır.

Destekleyen Kurum

Afyon Kocatepe Üniversitesi

Proje Numarası

20.FEN.BİL.10

Teşekkür

Bu çalışma Afyon Kocatepe Üniversitesi Bilimsel Araştırma Projeleri Komisyonu tarafından 20.FEN.BİL.10 numaralı Proje kapsamında desteklenmiştir.

Kaynakça

1. Soerjomataram I, Bray F, Wild CP, Weiderpass E, Stewart BW. World Cancer Report. Cancer research for cancer prevention. 2020.
2. Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1, 1st ed.; McGraw-Hill Education: New York, NY, USA.2017;416–19.
3. Nussbaumer S, Bonnabry P, Veuthey JL, Fleury-Souverain S. Analysis of anticancer drugs: a review. Talanta. 2011;85(5):2265-89.
4. YA L. Mechanisms of drug resistance in cancer chemotherapy. Cancer Drug Resist. 2005;14:34-48.
5. Kalyane D, Raval N, Maheshwari R, et al. Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. Mat. Sci. Eng. C. 2019;98:1252-76.
6. Cassatt DR, Winters TA, PrabhuDas M. Immune Dysfunction from Radiation Exposure. Radiat Res. 2023;200(4):389-95.
7. Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2019;2(2):141-60.
8. Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Int. J. Mol. Sci. 2020;21(9):3233.
9. Wu CP, Hsiao SH, Huang YH, et al. Sitravatinib sensitizes ABCB1-and ABCG2-overexpressing multidrug- resistant cancer cells to chemotherapeutic drugs. Cancers. 2020;12(1):195.
10. Nanayakkara AK, Follit CA, Chen G, Williams NS, Vogel PD, Wise JG. Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells. Scientific Reports. 2018;8(1):967.
11. Xu JL, Jin B, Ren ZH, et al. Chemotherapy plus erlotinib versus chemotherapy alone for treating advanced non-small cell lung cancer: a meta-analysis. PloS one. 2015;10(7):e0131278.
12. Lee JH, Nan A. Combination drug delivery approaches in metastatic breast cancer. J. Drug Deliv. 2012;2012(1):1-17.
13. Mokhtari RB, Homayouni TS, Baluch N, et al. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022-43.
14. Gong J, Shi T, Liu J, et al. Dual-drug codelivery nanosystems: An emerging approach for overcoming cancer multidrug resistance. Biomed. Pharmacother. 2023;161:114505.
15. Nakamura Y, Mochida A, Choyke PL, et al. Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer?. Bioconjugate Chem. 2016;27(10):2225-38.
16. Kim J, Cho H, Lim DK, et al. Perspectives for improving the tumor targeting of nanomedicine via the EPR effect in clinical tumors. Int. J. Mol. Sci. 2023;24(12):10082.
17. Alkaç İM, Keskin S, Çerçi B. Nanotaşiyicilarin kanser hücrelerine aktif ve pasif olarak hedeflenmesinde kullanilan yöntemler. Kocatepe Tıp Dergisi. 2024;25(3):396-406.
18. Wei X, Song M, Li W, et al. Multifunctional nanoplatforms co-delivering combinatorial dual-drug for eliminating cancer multidrug resistance. Theranostics. 2021;11(13):6334-54.
19. Zhang RX, Wong HL, Xue HY, et al. Nanomedicine of synergistic drug combinations for cancer therapy– Strategies and perspectives. J. Control. Release 2016;240:489-503.
20. Babos G, Biró E, Meiczinger M, Feczkó T. Dual drug delivery of sorafenib and doxorubicin from PLGA and PEG- PLGA polymeric nanoparticles. Polymers. 2018;10(8):895-902.
21. Karimian-Shaddel A, Dadashi H, Mashinchian M, et al. Codelivery of metformin and methotrexate with optimized chitosan nanoparticles for synergistic triple-negative breast cancer therapy in vivo. Int. J. Pharm. 2024;667:124897.
22. Elzayat EM, Sherif AY, Nasr FA, et al. Enhanced codelivery of gefitinib and azacitidine for treatment of metastatic-resistant lung cancer using biodegradable lipid nanoparticles. Materials. 2023;16(15):5364.
23. Rong J, Liu T, Yin X, et al. Co-delivery of camptothecin and MiR-145 by lipid nanoparticles for MRI-visible targeted therapy of hepatocellular carcinoma. J. Exp. Clin. Cancer Res. 2024;43(1):247.
24. Yadav PK, Saklani R, Tiwari AK, et al. Ratiometric codelivery of Paclitaxel and Baicalein loaded nanoemulsion for enhancement of breast cancer treatment. Int. J. Pharm. 2023;643:123209.
25. Imran M, Saleem S, Chaudhuri A, et al. Docetaxel: An update on its molecular mechanisms, therapeutic trajectory and nanotechnology in the treatment of breast, lung and prostate cancer. J. Drug Deliv. Sci. Technol. 2020;60:101959.
26. Griggs J, Hesketh R, Smith GA, et al. Combretastatin-A4 disrupts neovascular development in non- neoplastic tissue. Br. J. Cancer. 2001;84(6):832-5.
27. Zhang D, Liu L, Wang J, et al. Drug-loaded PEG-PLGA nanoparticles for cancer treatment. Front. Pharmacol. 2022;13:990505.
28. Sulaiman TN, Larasati D, Nugroho AK, et al. Assessment of the Effect of PLGA Co-polymers and PEG on the Formation and Characteristics of PLGA-PEG-PLGA Co-block Polymer Using Statistical Approach. Adv. Pharm. Bull. 2019;9(3):382-92.
29. Gref R, Minamitake Y, Peracchia MT, et al. Biodegradable long-circulating polymeric nanospheres. Science. 1994;263(5153):1600-3.
30. Tan CH, Huang ZJ, Huang XG. Rapid determination of surfactant critical micelle concentration in aqueous solutions using fiber-optic refractive index sensing. Anal. Biochem. 2010;401(1):144-7.
31. Elsey D, Jameson D, Raleigh B, Cooney MJ. Fluorescent measurement of microalgal neutral lipids. J. Microbiol. Methods. 2007;68(3):639-42.
32. Tajalli H, Gilani AG, Zakerhamidi MS, et al. The photophysical properties of Nile red and Nile blue in ordered anisotropic media. Dyes and Pigments. 2008;78(1):15-24.
33. Ray GB, Chakraborty I, Moulik SP. Pyrene absorption can be a convenient method for probing critical micellar concentration (cmc) and indexing micellar polarity. J. Colloid Interface Sci. 2006;294(1):248-54.
34. Kang RH, Kim NH, Kim D. A transformable and biocompatible polymer series using ring-opening polymerization of cyclic silane for more effective transdermal drug delivery. Chem. Eng. J. 2022;440:135989.
35. Nahar M, Jain NK. Preparation, characterization and evaluation of targeting potential of amphotericin B- loaded engineered PLGA nanoparticles. Pharm. Res. 2009;26:2588-98.
36. Wang Y, Chen H, Liu Y, et al. pH-sensitive pullulan-based nanoparticle carrier of methotrexate and combreta statin A4 for the combination therapy against hepatocellular carcinoma. Biomaterials. 2013;34(29):7181-90.
37. Rafiei P, Haddadi A. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile. Int. J. Nanomedicine. 2017:935-47.
38. Samkange T, D'Souza S, Obikeze K, Dube A. Influence of PEGylation on PLGA nanoparticle properties, hydrophobic drug release and interactions with human serum albumin.J. Pharm. Pharmacol. 2019;71(10):1497- 507.
39. Kaksonen M, Roux A. Mechanisms of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 2018;19(5):321.
40. Wang X, Li L, Song F. Interplay of nanoparticle properties during endocytosis. Crystals. 2021;11(7):728.
41. Digiacomo L, Renzi S, Pirrottina A, et al. PEGylation-Dependent Cell Uptake of Lipid Nanoparticles Revealed by Spatiotemporal Correlation Spectroscopy. ACS Pharmacol. Transl. Sci. 2024;7(10):3004-10.
42. Zhang Y, Sun C, Zhang Q, et al. Intranasal delivery of Paclitaxel encapsulated nanoparticles for brain injury due to Glioblastoma.J. Appl. Biomater. Funct. Mater. 2020;18:2280800020977170.
43. Redrado M, Xiao Z, Upitak K,et al. Applications of biodegradable polymers in the encapsulation of anticancer metal complexes. Adv. Funct. Mater. 2024;34(36):2401950.
44. Zaid AN, Hassan M, Jaradat N, et al. Formulation and characterization of combretastatin A4 loaded PLGA nanoparticles. Materials Research Express. 2020;6(12):1250d7.
45. Bariwal J, Kumar V, Chen H, et al. Nanoparticulate delivery of potent microtubule inhibitor for metastatic melanoma treatment. J Control Release. 2019;309:231-43.
46. Noori Koopaei M, Khoshayand MR, Mostafavi SH, et al. Docetaxel Loaded PEG-PLGA Nanoparticles: Optimized Drug Loading, In-vitro Cytotoxicity and In-vivo Antitumor Effect. Iran J Pharm Res. 2014;13(3):819-33.
47. Wu J. The enhanced permeability and retention (EPR) effect: the significance of the concept and methods to enhance its application. J. Pers. Med. 2021;11(8):771.

Toplam 47 adet kaynakça vardır.

Ayrıntılar

Birincil Dil	İngilizce
Konular	Kanser Hücre Biyolojisi, Kanser Tedavisi (Kemoterapi ve Radyoterapi hariç), Nanoilaç
Bölüm	Makaleler-Araştırma Yazıları
Yazarlar	Sadık Kağa 0000-0002-6303-7981 Didem Kesgin 0000-0002-0624-2196 Elif Kağa 0000-0002-2279-6105
Proje Numarası	20.FEN.BİL.10
Yayımlanma Tarihi	16 Temmuz 2025
Gönderilme Tarihi	14 Nisan 2025
Kabul Tarihi	29 Mayıs 2025
Yayımlandığı Sayı	Yıl 2025 Cilt: 26 Sayı: 3

Kaynak Göster

APA	Kağa, S., Kesgin, D., & Kağa, E. (2025). THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS. Kocatepe Tıp Dergisi, 26(3), 262-271. https://doi.org/10.18229/kocatepetip.1676373
AMA	Kağa S, Kesgin D, Kağa E. THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS. KTD. Temmuz 2025;26(3):262-271. doi:10.18229/kocatepetip.1676373
Chicago	Kağa, Sadık, Didem Kesgin, ve Elif Kağa. “THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS”. Kocatepe Tıp Dergisi 26, sy. 3 (Temmuz 2025): 262-71. https://doi.org/10.18229/kocatepetip.1676373.
EndNote	Kağa S, Kesgin D, Kağa E (01 Temmuz 2025) THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS. Kocatepe Tıp Dergisi 26 3 262–271.
IEEE	S. Kağa, D. Kesgin, ve E. Kağa, “THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS”, KTD, c. 26, sy. 3, ss. 262–271, 2025, doi: 10.18229/kocatepetip.1676373.
ISNAD	Kağa, Sadık vd. “THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS”. Kocatepe Tıp Dergisi 26/3 (Temmuz 2025), 262-271. https://doi.org/10.18229/kocatepetip.1676373.
JAMA	Kağa S, Kesgin D, Kağa E. THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS. KTD. 2025;26:262–271.
MLA	Kağa, Sadık vd. “THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS”. Kocatepe Tıp Dergisi, c. 26, sy. 3, 2025, ss. 262-71, doi:10.18229/kocatepetip.1676373.
Vancouver	Kağa S, Kesgin D, Kağa E. THERAPEUTIC EFFICACY OF DOCETAXEL AND COMBRETASTATIN A4 LOADED PEG-PLGA NANOPARTICLES IN HUMAN BREAST CANCER CELLS. KTD. 2025;26(3):262-71.

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