{"title":"Dendrimer nanoclusters loaded with gold nanoparticles for enhanced tumor CT imaging and chemotherapy via an amplified EPR effect","authors":"Shewaye Lakew Mekuria, Gaoming Li, Zhiqiang Wang, Wubshet Mekonnen Girma, Aiyu Li, Meijuan He, Han Wang, Meera Moydeen Abdul Hameed, Mohamed EL-Newehy, Xiangyang Shi, Mingwu Shen","doi":"10.1039/d4tb01747a","DOIUrl":null,"url":null,"abstract":"The design of efficient multifunctional nanomedicines to overcome adverse side effects within biological systems and to achieve desirable computed tomography (CT) imaging and therapeutics of tumors remains challenging. Herein, we report the design of multifunctional nanoclusters (NCs) based on generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers. In brief, G3 dendrimers were crosslinked with 4,4′-dithiodibutryic acid (DA) to generate disulfide-bond-containing dendrimer nanoclusters (DNCs), functionalized with 1,3-propane sultone (1,3-PS) to be zwitterionic, <em>in situ</em> loaded with gold nanoparticles (Au NPs), and finally encapsulated with the drug doxorubicin (DOX). The designed DOX/Au@DNCs-PS possess a favorable colloidal stability with a hydrodynamic size of 249.4 nm, a redox-responsive drug release profile, and enhanced cellular uptake <em>in vitro</em>. We show that DOX/Au@DNCs-PS have a greater DOX penetration and growth inhibition of three-dimensional (3D) tumor spheroids than the single dendrimer counterpart in vitro. Furthermore, the developed Au@DNCs-PS enable a better Au-mediated X-ray attenuation property than the single dendrimer counterpart material. Likely due to the amplified enhanced permeability and retention (EPR) effect, the created Au@DNCs-PS and DOX/Au@DNCs-PS enable better CT imaging and chemotherapeutic effect of a mouse breast tumor model, respectively, than the single dendrimer counterparts. With its proven biocompatibility, the constructed formulation may hold promising potential for development for different cancer nanomedicine applications.","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Materials Chemistry B","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1039/d4tb01747a","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
The design of efficient multifunctional nanomedicines to overcome adverse side effects within biological systems and to achieve desirable computed tomography (CT) imaging and therapeutics of tumors remains challenging. Herein, we report the design of multifunctional nanoclusters (NCs) based on generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers. In brief, G3 dendrimers were crosslinked with 4,4′-dithiodibutryic acid (DA) to generate disulfide-bond-containing dendrimer nanoclusters (DNCs), functionalized with 1,3-propane sultone (1,3-PS) to be zwitterionic, in situ loaded with gold nanoparticles (Au NPs), and finally encapsulated with the drug doxorubicin (DOX). The designed DOX/Au@DNCs-PS possess a favorable colloidal stability with a hydrodynamic size of 249.4 nm, a redox-responsive drug release profile, and enhanced cellular uptake in vitro. We show that DOX/Au@DNCs-PS have a greater DOX penetration and growth inhibition of three-dimensional (3D) tumor spheroids than the single dendrimer counterpart in vitro. Furthermore, the developed Au@DNCs-PS enable a better Au-mediated X-ray attenuation property than the single dendrimer counterpart material. Likely due to the amplified enhanced permeability and retention (EPR) effect, the created Au@DNCs-PS and DOX/Au@DNCs-PS enable better CT imaging and chemotherapeutic effect of a mouse breast tumor model, respectively, than the single dendrimer counterparts. With its proven biocompatibility, the constructed formulation may hold promising potential for development for different cancer nanomedicine applications.
期刊介绍:
Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive:
Antifouling coatings
Biocompatible materials
Bioelectronics
Bioimaging
Biomimetics
Biomineralisation
Bionics
Biosensors
Diagnostics
Drug delivery
Gene delivery
Immunobiology
Nanomedicine
Regenerative medicine & Tissue engineering
Scaffolds
Soft robotics
Stem cells
Therapeutic devices