Publication: Quantifaction of polymer-cell adhesion force using atomic force microscopy for tumor targeting
Abstract
TÜMÖR HEDEFLEME İÇİN ATOMİK KUVVET MİKROSKOBU KULLANARAK POLİMER-HÜCRE ADEZYON KUVVETİNİN ÖLÇÜMÜ Yeni tasarlanan ilaç taşıyıcı sistemler ve Atomik Kuvvet Mikroskobu (AFM) uygulamaları inanılmaz ilgi görmektedir. İlaç taşıyıcı sistemlerde (DDS), aktif/ pasif DDS hazırlamak için FDA onaylı bileşikler tercih edilir. Bu çalışmada, lipit bazlı çekirdek-kabuk yapılı bir nano-ilaç taşıyıcı sistem (NDDS) hazırlanmıştır. İlk olarak, bir katyon değiştirme mekanizması kullanılarak lesitin (Lec) ve sodyum asetat (NaOAc) kompleksleri hazırlandı. Katyonik polimerler (kabuk) oluşturmak için hyaluronik asit (Ha), kitosan (Ch) ve inülin (In), GTMAC ajanı ile kuaternizasyon reaksiyonları yoluyla reaksiyona sokuldu. Lec-OAc kompleksi (çekirdek), çekirdek-kabuk yapılı miseller üretmek için katyonik polimerlerle (QHa, QCh ve QIn) kaplandı. Antikanser ilaçları olarak, Paklitaksel (PTX) ve kurkumin (Cur), çekirdek-kabuk yapılı misellere dahil edildi. İlaç yüklü çekirdek-kabuk yapılı miseller, FTIR, DSC, NMR, Dinamik Işık Saçılımı (DLS) ve SEM&TEM kullanılarak karakterize edildi. DLS sonuçları, üretilen çekirdek-kabuk yapılı misellerin 100 nm ila 800 nm arasında uygun bir parçacık boyutu aralığına ve uygun zeta değerlerinin -5.0 mV ila-25.6 mV arasında olduğunu göstermiştir. Zeta değerleri katyonik polimer kaplama aşamasının başarılı olduğunu göstermiştir. DSC sonuçları, ilaçların başarılı bir şekilde dahil edilmesiyle Cur ve Ptx'in erime noktalarının kaybolduğunu göstermektedir. İlaç salım kinetiği sonuçlarına göre oluşturulan NDDS, ilaç salımının difüzyon yoluyla gerçekleştiğini öne süren Korsmeyer-Peppas matematiksel modeline uymaktadır. MDA-MB231 kanser hattı in vitro sitotoksisite değerlendirmesine göre, katyonik polimer kabuklar, tasarlanmış lipid bazlı çekirdek-kabuk yapılı miseller için başarılı hücre alımı ve üstün toksik profil sağlamaktadır. Bu nedenle üretilen NDDS, kanser tedavisi için potansiyel bir adaydır. Polimer-hücre adezyon kuvveti ölçümü, polimer hücre etkileşimlerini aydınlatmak ve kansere karşı hedeflenen DDS'yi tasarlamak için çok önemlidir. Ha, Ch ve In, tiyomerlerin güçlü adezif özelliklerinden dolayı tiyollenme reaksiyonları ile tiyolleştirilmiştir. Altın AFM kentilevırını kaplamak için tiyomerler kullanıldı. Modifiye AFM kentilevırı ve çeşitli kanser hücreleri arasında kuvvet-mesafe ölçümleri yapıldı. Sonuçlar, artan polimer hücre adezyonlarının hücre tipine, reseptöre, polimerik moleküler ağırlığa ve polimer tipine bağlı olduğunu göstermektedir.
QUANTIFACTION OF POLYMER-CELL ADHESION FORCE USING ATOMIC FORCE MICROSCOPY FOR TUMOR TARGETING Newly designed drug delivery systems and Atomic Force Microscopy (AFM) applications have gained incredible attention. In drug delivery systems (DDS), FDA-approved compounds are preferable to preparation active/ passive DDS. In this study, a lipid-based core-shell structured nano-drug delivery system (NDDS) was prepared. Firstly, Lecithin (Lec) and sodium acetate (NaOAc) complexes were prepared using a cation exchange mechanism. In order to generate cationic polymers (shell), hyaluronic acid (Ha), chitosan (Ch), and inulin (In) were reacted with the GTMAC agent via quaternization reactions. The Lec-OAc complex (core) was coated with cationic polymers (QHa, QCh, and QIn) to produce core-shell structured micelles. As anticancer drugs, Paclitaxel (PTX) and cur (Cur) were incorporated in core-shell structured micelles. The drug-loaded core-shell structured micelles were characterized using FTIR, DSC, NMR, Dynamic Light Scattering (DLS), and SEM&TEM. DLS results showed that the produced core-shell structured micelles have a suitable particle size range of 100 nm to 800 nm and suitable zeta values range from -5.0 mV to -25.6 mV. The zeta values showed that the cationic polymer coating stage was successful. The DSC results showed that the melting peaks of Cur and Ptx disappeared due to the successful incorporation of drugs. According to the drug release kinetics results, the generated NDDS fits Korsmeyer-Peppas mathematical model, which suggests that drug release occurs via diffusion. According to the in vivo cytotoxicity assessment of the MDA-MB231 cancer line, cationic polymer coatings provided successful cell internalization and superior toxic profile to designed lipid-based core-shell structured micelles. Therefore, the produced NDDS was a potential candidate for cancer therapy. Polymer-cell adhesion force measurement is crucial to enlighten polymer-cell attractions, and design targeted DDS against cancer. Ha, Ch, and In were thiolated via thiolation reactions due to the strong adhesive properties of thiomers. Thiomers were used to coat the golden AFM cantilever. Force-distance measurements were performed between the modified AFM cantilever and various cancer cells. The results showed that increasing polymer-cell adhesions mainly depended on cell type, receptor, polymeric molecular weight, and polymer type.
QUANTIFACTION OF POLYMER-CELL ADHESION FORCE USING ATOMIC FORCE MICROSCOPY FOR TUMOR TARGETING Newly designed drug delivery systems and Atomic Force Microscopy (AFM) applications have gained incredible attention. In drug delivery systems (DDS), FDA-approved compounds are preferable to preparation active/ passive DDS. In this study, a lipid-based core-shell structured nano-drug delivery system (NDDS) was prepared. Firstly, Lecithin (Lec) and sodium acetate (NaOAc) complexes were prepared using a cation exchange mechanism. In order to generate cationic polymers (shell), hyaluronic acid (Ha), chitosan (Ch), and inulin (In) were reacted with the GTMAC agent via quaternization reactions. The Lec-OAc complex (core) was coated with cationic polymers (QHa, QCh, and QIn) to produce core-shell structured micelles. As anticancer drugs, Paclitaxel (PTX) and cur (Cur) were incorporated in core-shell structured micelles. The drug-loaded core-shell structured micelles were characterized using FTIR, DSC, NMR, Dynamic Light Scattering (DLS), and SEM&TEM. DLS results showed that the produced core-shell structured micelles have a suitable particle size range of 100 nm to 800 nm and suitable zeta values range from -5.0 mV to -25.6 mV. The zeta values showed that the cationic polymer coating stage was successful. The DSC results showed that the melting peaks of Cur and Ptx disappeared due to the successful incorporation of drugs. According to the drug release kinetics results, the generated NDDS fits Korsmeyer-Peppas mathematical model, which suggests that drug release occurs via diffusion. According to the in vivo cytotoxicity assessment of the MDA-MB231 cancer line, cationic polymer coatings provided successful cell internalization and superior toxic profile to designed lipid-based core-shell structured micelles. Therefore, the produced NDDS was a potential candidate for cancer therapy. Polymer-cell adhesion force measurement is crucial to enlighten polymer-cell attractions, and design targeted DDS against cancer. Ha, Ch, and In were thiolated via thiolation reactions due to the strong adhesive properties of thiomers. Thiomers were used to coat the golden AFM cantilever. Force-distance measurements were performed between the modified AFM cantilever and various cancer cells. The results showed that increasing polymer-cell adhesions mainly depended on cell type, receptor, polymeric molecular weight, and polymer type.