Multifunctional Self-assembled Nanoparticles For Targeted Delivery And Tumor Therapy

With the development of nanomedicine and supramolecular chemistry,more and more functions have been integrated into one nanosystem to improve the therapeutic effect of cancer and other serious diseases.Therefore,how to efficiently and flexibly construct a multifunctional nanosystem has become the focus in the related research fields.In supramolecular chemistry,various noncovalent interactions contribute to the acquisition of functional nanomaterials under mild conditions.Especially,it is favourable to precisely control the targeted release of drugs or prodrugs when introducing thermosensitive biomolecules,which could overcome the limitations of traditional therapies.Hence,in the dissertation,cyclodextrin polymer,drugs and aptamer are used to form multifunctional nanoparticles through hydrophilic interactions and host-guest interactions,which have functions of multiple drugs loading,cell imaging and drug targeted delivery.The research work of this dissertation included the following two parts:1.Self-assembled nanoparticles loaded multidrug based on β-cyclodextrin polymer for synergistic cancer therapyA self-assembled supramolecular nanoparticle(DOX/HCPT/DTX@poly-β-CD)was formulated by combining multidrug(DOX: doxorubicin;HCPT: 10-hydroxycamptothecine;DTX: docetaxel)into β-cyclodextrin polymer(poly-β-CD)through host-guest interactions,which was a flexible nanoplatform for synergistic cancer therapy.The scanning electron microscopy showed that the DOX/HCPT/DTX@poly-β-CD nanoparticle was in the shape of sphere.The hydraulic diameter of nanoparticle was about 140 nm by dynamic light scattering.The flow cytometry results showed that intracellular fluresencence intensity was gradually enhanced with culture time in cells treated with nanoparticles,and the fluresencence intensity of nanoparticles was stronger than that of free DOX under the same conditions.MCF-7 cells and SMMC-7721 cells were selected to investigate the synergistic effect of the three drugs,and MTS analysis indicated the three drugs had a good synergistic effect.Moreover,the poly-β-CD exhibited an excellent biocompatibility,which concentration increased to 2.5 mM and the cell viability was still above 90%.2.Multifunctional self-assembled nanoparticles based on β-cyclodextrin polymer as nanocarrier for targeted delivery and combination chemotherapyOn the basis of the above research work,a multifunctional self-assembled supramolecular nanoparticle(T-SSNP)based on β-cyclodextrin polymer as carrier was constructed by introducing aptamer for targeted delivery and selective cytotoxicity.T-SSNP was formed by self-assembled interactions among three elements:(1)β-cyclodextrin polymer(poly-β-CD),as the nanocarrier;(2)two kinds of antitumor drugs-doxorubicin(DOX)and docetaxel(DTX);(3)aptamers labeled with adamantane and fluorescein(Ad-aptamer-FAM),as the recognition elements.The hydrophobic DTX and DOX were combined into nanoparticles via host-guest interactions to prepare self-assembled supramolecular nanoparticles(SSNPs).Finally,the Ad-aptamer-FAM was labeled on the surface of nanoparticles.The flow cytometry results showed that the T-SSNPs could specifically recognize targeted cells and the signal-to-background ratio of T-SSNPs was 6.6,which was about 1.5 times than that of the free aptamers(the signal-to-background ratio was 4.5).The synergistic effect of the two drugs was confirmed by MTS,and the results indicated that combination drugs had a good synergistic effect with a combination index(CI)of 0.43 under the condition of 50% cell viability.As evidenced by MTS assay,the T-SSNPs exhibited significant selective cytotoxicity toward targeted cells.Moreover,the poly-β-CD exhibited excellent biocompatibility,which was almost no toxicity to cells in a certain concentration range.Thus,an effective and simple drug delivery system was constructed for targeted delivery and combination chemotherapy.