CD44 and CD221 directed magnetic cubosomes for the targeted delivery of helenalin to rhabdomyosarcoma cells  

作　　者：Hakmin Mun Yuriy Chaban Tanveer A.Tabish Nanasaheb Thorat Nathan Cowieson CDavid Owen Helen E.Townley 

机构地区：[1]Nuffield Department of Women’s and Reproductive health,University of Oxford,Oxford OX39DU,UK [2]Electron Bio-Imaging Centre,Diamond Light Source,Didcot OX110DE,UK [3]Radcliffe Department of Medicine,University of Oxford,Oxford OX37BN,UK [4]B21,Diamond Light Source,Didcot OX110DE,UK [5]Department of Engineering Science,University of Oxford,Oxford OX13PJ,UK

出　　处：《Nano Research》2023年第2期2915-2926,共12页纳米研究（英文版）

基　　金：supported by the Pyongyang University of Science and Technology(PUST)-UK scholarship,the Williams Fund(Oxford Hospitals Charity,No.0085);the UK national electron bio-imaging centre(No.NT32452);the Marie Sklodowska–Curie Grant Agreement(No.840964).

摘　　要：Confining chemotherapy to tumour sites by means of active targeting nanoparticles(NPs)may increase the treatment effectuality while reducing potential side effects.Cubosomes are one of the next-generation drug delivery nanocarriers by virtue of their biocompatibility and bioadhesion,sizeable payload encapsulation and high thermostability.Herein,an active tumour targeting system towards rhabdomyosarcoma(RMS)cells was evaluated.Cubosomes were loaded with helenalin(a secondary metabolite from Arnica plants),which we have previously shown to induce apoptosis in RMS cells.The functionalization of the cubosomes was accomplished to enable binding to membrane receptors and translocation under a magnetic field.RMS cells overexpress CD44 and CD221 on their membrane surface and,therefore,hyaluronic acid(HA,a ligand for CD44)and antibodies(Abs)against CD221 were coupled to cubosomes via electrostatic attraction and the thiol-Michael reaction,respectively.Magnetization of the cubic phase NPs was achieved by embedding superparamagnetic iron oxide NPs(SPIONPs)into the cubic matrix.Single-function and multi-function cubosomes had Im3m cubic phase structures with well-organized lattice patterns.Conjugation with 2%HA or anti-CD221 half Abs and/or 1%SPIONPs showed significantly higher uptake into RMS cells compared to unfunctionalized cubosomes.CD44 and CD221 directed magnetic(triple-function)cubosomes were capable of internalizing into RMS cells in an energy-independent mechanism.Helenalin-laden triple functionalized cubosomes showed limited impact on the viability of control fibroblast cells,while they induced a high degree cytotoxicity against RMS cells.Profound tumour cell death was observed in both two-dimensional(2D)culture and three-dimensional(3D)tumour spheroids.

关 键 词：CUBOSOME active targeting RHABDOMYOSARCOMA helenalin nanoparticle functionalization 

分 类 号：R730.5[医药卫生—肿瘤]