Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core.

作者: Xia Li , Manpreet Sambi , Alexandria DeCarlo , Sergey V. Burov , Roman Akasov

DOI: 10.3390/NANO8080588

关键词:

摘要: Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront cancer research, having engineered for safer, more efficient and effective use chemotherapy treatment cancer. However, selective targeting choosing right surface biomarker are critical targeted work. Currently, available systems two-dimensional monolayer test efficacy system, but designing be specific in vivo penetrate inner core remains major design challenge. These challenges can overcome by using study model that integrates three-dimensional aspect culture system. Here, we tested functionalized folic acid-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via biodegradable linker 2,4-diaminobutyric acid (DABA) avascular human pancreatic breast spheroids culture. The was quantitatively analyzed its hydrophobic encapsulation efficiency three different chemical structures with molecular weights. Their release profiles properties various concentrations pH environments were also characterized. Using anticancer curcumin two standard clinical chemotherapeutic drugs, paclitaxel 5-fluorouracil, ability FA-DABA-SMA nanoparticles encapsulate differently sized drugs deliver them kill WST-1 cell proliferation assay. findings this revealed shows unique as an active tumor-targeting internalize chemotherapeutics killing cells. novelty is first demonstrate encapsulated effectively penetrating reducing their volumes dose- time-dependent manner.

参考文章(39)
Hilary Shmeeda, Lidia Mak, Dina Tzemach, Peleg Astrahan, Mark Tarshish, Alberto Gabizon, Intracellular uptake and intracavitary targeting of folate-conjugated liposomes in a mouse lymphoma model with up-regulated folate receptors. Molecular Cancer Therapeutics. ,vol. 5, pp. 818- 824 ,(2006) , 10.1158/1535-7163.MCT-05-0543
Kavirayani Priyadarsini, The Chemistry of Curcumin: From Extraction to Therapeutic Agent Molecules. ,vol. 19, pp. 20091- 20112 ,(2014) , 10.3390/MOLECULES191220091
PengWei Dong, XiuHong Wang, YingChun Gu, YuJun Wang, YingJing Wang, ChangYang Gong, Feng Luo, Gang Guo, Xia Zhao, YuQuan Wei, ZhiYong Qian, Self-assembled biodegradable micelles based on star-shaped PCL-b-PEG copolymers for chemotherapeutic drug delivery Colloids and Surfaces A: Physicochemical and Engineering Aspects. ,vol. 358, pp. 128- 134 ,(2010) , 10.1016/J.COLSURFA.2010.01.037
Carolyn L. Waite, Charles M. Roth, PAMAM-RGD conjugates enhance siRNA delivery through a multicellular spheroid model of malignant glioma. Bioconjugate Chemistry. ,vol. 20, pp. 1908- 1916 ,(2009) , 10.1021/BC900228M
Vanda Boshnjaku, Kyu-Won Shim, Takao Tsurubuchi, Shunsuke Ichi, Elise V. Szany, Guifa Xi, Barbara Mania-Farnell, David G. McLone, Tadanori Tomita, C. Shekhar Mayanil, Nuclear localization of folate receptor alpha: a new role as a transcription factor. Scientific Reports. ,vol. 2, pp. 980- 980 ,(2012) , 10.1038/SREP00980
C. Malardier-Jugroot, T. G. M. van de Ven, T. Cosgrove, R. M. Richardson, M. A Whitehead, Novel self-assembly of amphiphilic copolymers into nanotubes: characterization by small-angle neutron scattering. Langmuir. ,vol. 21, pp. 10179- 10187 ,(2005) , 10.1021/LA050888A
Wadih Arap, Renata Pasqualini, Erkki Ruoslahti, Cancer Treatment by Targeted Drug Delivery to Tumor Vasculature in a Mouse Model Science. ,vol. 279, pp. 377- 380 ,(1998) , 10.1126/SCIENCE.279.5349.377