A Comparative Study of Passive and Active Tumor Targeting Using Nanoparticles as Drug Delivery Systems

Abstract

Nanoparticle-mediated drug targeting is an active area of cancer research and hold enormous potential in improving anticancer efficacy by providing tumor tissue specificity. Herein, tumor targeting capabilities of nanoparticles between passive targeting approach via the enhanced permeability and retention (EPR) effect and active targeting approach via the biotin receptors were compared to determine targeting efficiency rates. For this reason, Fe₃O₄@SiO₂(FITC)-DOX (for passive targeting) and Fe₃O₄@SiO₂(FITC)-BTN/DOX (for active targeting) multifunctional nanoparticles combining imaging and therapy were used. Fluorescence microscopy and flow cytometry were employed to both visualize and quantify the accumulation of nanoparticles into the tumor cells. The results demonstrated that active targeting strategy considerably enhanced nanoparticle accumulation in the cervical carcinoma HeLa cells with a 2-fold increase in comparison to passive targeting. Targeted nanoparticles exhibited higher cytotoxicity in cancer cells with an approximately 2.5-fold better half maximal inhibitory concentration (IC₅₀) value than untargeted nanoparticles. Moreover, it was found that targeted nanoparticles increased the number of apoptotic cells by nearly 21.1% as compared to untargeted nanoparticles. These observations show that active tumor targeting drug delivery systems could be more promising for enhancing the chemotherapeutic effects of anticancer drugs as compared to passive tumor targeting drug delivery systems.

Keywords

• Cancer,multifunctional nanoparticles,passive targeting,active targeting

İlaç Taşıma Sistemleri olarak Nanopartiküller kullanılarak Pasif ve Aktif Tümör Hedeflemelerinin Karşılaştırmalı İncelenmesi

Abstract

Nanopartikül-aracılı ilaç hedefleme kanser araştırmalarının aktif bir alanı olup, tümör dokusuna özgün antikanser etkinliği artırmada çok önemli bir potansiyele sahiptir. Bu çalışmada, hedefleme verimlilik oranlarının belirlenmesi için pasif ve aktif hedefli nanopartiküllerin tümör hedefleme kabiliyetleri, sırasıyla artmış geçirgenlik ve alıkonma (EPR) etkisi ve biyotin reseptörlerini hedefleme yaklaşımları karşılaştırılarak incelendi. Bunun için, görüntüleme ve tedavi edici özellikleri bir arada barından Fe₃O₄@SiO₂(FITC)-DOX (pasif hedefleme için) ve Fe₃O₄@SiO₂(FITC)-BTN/DOX (aktif hedefleme için) multifonksiyonel nanopartikülleri kullanıldı. Nanopartiküllerin tümör hücrelerindeki birikiminin izlenmesi ve miktarsal ölçümü için floresan mikroskopu ve akım sitometresi kullanıldı. Elde edilen sonuçlar, pasif hedeflemeyle karşılaştırıldığında aktif hedefleme stratejisinin servikal karsinoma HeLa hücrelerindeki nanopartikül birikimini 2 kat gibi önemli bir ölçüde artırdığını gösterdi. Aktif hedefli nanopartiküller, pasif hedefli nanopartikülerden yaklaşık 2.5 kat daha düşük yarı-maksimum inhibisyon konsantrasyonu (IC₅₀) değeri ile kanser hücrelerinde daha yüksek sitotoksisite sergiledi. Ayrıca, pasif hedefli nanopartiküllerle karşılaştırıldığında, aktif hedefli nanopartiküllerin apoptotik hücre sayısını yaklaşık % 21.1 oranında artırdığı bulundu. Bu gözlemler, aktif tümör hedefli ilaç taşıma sistemlerinin, pasif tümör hedefli ilaç taşıma sistemleri ile karşılaştırıldığında, antikanser ilaçların kemoterapötik etkilerini artırmada daha umut verici olduğunu göstermektedir.

Keywords

• Kanser,multifonksiyonel nanopartiküller,pasif hedefleme,aktif hedefleme

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