Synthesis and Characterization of AICAR and DOX Conjugated Multifunctional Nanoparticles as a Platform for Synergistic Inhibition of Cancer Cell Growth

Abstract

The success of cancer treatment depends on the response to chemotherapeutic agents. However, malignancies often acquire resistance to drugs if they are used frequently. Combination therapy involving both a chemotherapeutic agent and molecularly targeted therapy may have the ability to retain and enhance therapeutic efficacy. Here, we addressed this issue by examining the efficacy of a novel therapeutic strategy that combines AICAR and DOX within a multifunctional platform. In this context, we reported the bottom-up synthesis of Fe 3 O 4 @SiO 2 (FITC)-FA/AICAR/ DOX multifunctional nanoparticles aiming to neutralize survivin (BIRC5) to potentiate the efficacy of DOX against chemoresistance. The structure of nanoparticles was characterized by dynamic light scattering (DLS), zeta-potential measurement, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and electron microscopy (SEM and STEM with EDX) techniques. Cellular uptake and cytotoxicity experiments demonstrated preferentially targeted delivery of nanoparticles and an efficient reduction of cancer cell viability in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat, and MIA PaCa-2). These results indicate that the multifunctional nanoparticle system possesses high inhibitory drug association and sustained cytotoxic effect with good biocompatibility. This novel approach which combines AICAR and DOX within a single platform might be promising as an antitumor treatment for cancer.

Current Status and Perspectives of Protease Inhibitors and Their Combination with Nanosized Drug Delivery Systems for Targeted Cancer Therapy

“…100 These have been developed as an all-in-one biomedical platform with proposed configurations with (i) significantly improved stability and solubility of treatments, (ii) prevention of degradation or premature interactions, (iii) improved drug absorption, (iv) targeted delivery of the drug to specific tissues, cells or subcellular compartments, (v) controlled drug distribution and pharmacokinetics. 101,102 Furthermore, by engineering the NP formulations, more properties could be incorporated into the NPs according to requirements of disease states, such as multi-drug coadministration, programmed drug-delivery or triggered drug release, thereby reducing adverse effects of inhibitor/ drug combinations to the healthy tissues or organs and improving the quality of life for patients. 101,102 Consequently, in this context, formulating protease inhibitors with nanostructured carriers presents new perspectives on protease-targeted cancer therapies.…”

İnsan Kolon Kanseri Hücrelerine Karşı İnorganik Nanopartikül-Temelli İlaç Taşıyıcı Sistemlerin Kullanılması: Partikül Büyüklüğünün Antikanser Aktivitesine Etkisi

“…Bunun nedeni olarak, küçük partiküllerin hücresel alım verimliliklerinin daha yüksek olduğundan bahsedebileceğimiz gibi, küçük partiküllerin yüzey alanı/hacim oranı büyük partiküllere göre daha büyük olduğundan ilaç salınım hızları daha yüksel olmaktadır, fakat büyük partiküller sahip oldukları büyük çekirdek yapıları sayesinde daha fazla ilaç yüklemesine olanak sağlarken daha yavaş bir ilaç salınım karakteri gösterdiklerinden sitotoksik etkileri ancak zamana bağımlı olarak artış göstermektedir [14][15]. Benzer bir şekilde daha önce yaptığımız çalışmalarda da, ilaç taşıma sistemleri olarak tasarladığımız nanopartiküller, biyokimyasal profilleri birbirlerinden farklı olan çeşitli kanser hücrelerine karşı değişen oranlarda sitotoksik etki sergilemiştir [16][17][18][20][21].…”

“…Bu bilgiler ışığında bu çalışmada, ilaç taşıyıcı sistemleri olarak 100 nm'den küçük ve büyük olmak üzere iki farklı büyüklükteki nanopartiküllerin (~ 55 ve 314 nm) insan kolon kanseri Caco-2 ve HCT-116 hücrelerine karşı göstermiş oldukları antikanser aktiviteleri araştırıldı. Bunun için, yapısı daha önceki çalışmalarımızda geliştirilen ve fizikokimyasal olarak karakterize edilen bir antikanser ilaç taşıyıcı sistem olan Fe3O4@SiO2(FITC)-BTN/DOX multifonksiyonel nanopartikül formülasyonları kullanıldı [16][17][18]. İlgili nanopartiküllerin, antikanser etkinlikleri, iki farklı insan kolon kanseri hücrelerine karşı göstermiş oldukları (1) hücresel alım, (2) floresan görüntüleme, (3) sitotoksik ve (4) proapoptotik etkileri araştırılarak karşılaştırıldı.…”

Anticancer drug delivery systems based on inorganic nanocarriers with fluorescent tracers

“…Besides, the silica shell can ensure an enough distance between the Fe 3 O 4 core and fluorescent tracers to prevent the fluorescence quenching effect. For example, the fluorescent signals of fluorescent dyes modified on the surface of silica shell or encapsulated with silica could track the process of targeted drug delivery by fluorescence microscopy . In addition, silica exhibits a negative surface charge under physiological condition, and the silanol groups make the particle surfaces lyophilic, thus, enhancing the stability of their suspensions, even when the pH or electrolyte concentrations are changed …”