Environmentally Responsive Dual-Targeting Nanoparticles: Improving Drug Accumulation in Cancer Cells as a Way of Preventing Anticancer Drug Efflux

Abstract

Drug targeting and stimuli-responsive drug release are 2 active areas of cancer research and hold tremendous potential in the management of cancer drug resistance. In this study, I addressed this issue and focused on the synthesis and characterization of pH-responsive FeO@SiO(FITC)-BTN/folic acid/DOX multifunctional nanoparticles aiming to increase drug accumulation in malignancies with both dual active targeting and endosomal drug release properties. Dye-doped silica magnetic-fluorescent composite was constructed by a simple coprecipitation of Fe/Fe salts followed by sol-gel formation and dual-targeting function was obtained by conjugating folate and biotin moieties on the silica surface of nanoparticles via an esterification reaction. Doxorubicin was then successfully attached on the amine-functionalized nanoparticles using a pH-sensitive Schiff-base formation. The physicochemical characterization of the structure was performed by dynamic light scattering, zeta potential measurement, X-ray diffraction, Fourier transform infrared spectroscopy, electron microscopy techniques, and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated an enhanced intracellular delivery and reduction of cancer cell viability in the cervical carcinoma HeLa cell line. Furthermore, proapoptotic studies showed that the nanoparticles increased the apoptotic rates within the same cancer cells. The preliminary cell tests confirm the potential of these multifunctional nanoparticles against the development of drug resistance in cancer cells.

<p>Preparation and Evaluation of Doxorubicin-Loaded PLA–PEG–FA Copolymer Containing Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for Cancer Treatment: Combination Therapy with Hyperthermia and Chemotherapy</p>

“…The folic acid linked-nanocarriers could further enhance the accumulation level and drug release rate in tumor area reported in a previous study by Daglioglu. 32 Therefore, folic acid conjugated polymers can be used to increase the specificity and cellular uptake of anti-cancer drugs in tumor cells through receptor-mediated endocytosis by folate receptors. 33 , 34 Doxorubicin (DOX) is one of the most effective antitumor drugs for solid tumors including breast, ovarian, lung and prostatic cancers.…”

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.…”

tLyP-1 Peptide Functionalized Human H Chain Ferritin for Targeted Delivery of Paclitaxel

“…Due to their unique properties such as the inherent biological origins, bioactivity, biocompatibility and biodegradability, peptides have promising applications in the fields of drug delivery. [22][23][24][25][26] The modification of nanocarriers with cell-penetrating peptides (CPPs) provides an alternative strategy to solve the problem of impermeable tumor tissue. The modified CPPs can dramatically improve the drug penetration efficiency, promote endosomal escape, enhance the stability of the drug in the blood, improve the specific targeting of the tumor, and provide the controlled drug release by using the stimulation response mechanism in tumor microenvironments.…”