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Dendrimer nanoclusters loaded with gold nanoparticles for enhanced tumor CT imaging and chemotherapy via an amplified EPR effect.
- Source :
-
Journal of materials chemistry. B [J Mater Chem B] 2024 Oct 02; Vol. 12 (38), pp. 9524-9532. Date of Electronic Publication: 2024 Oct 02. - Publication Year :
- 2024
-
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.
- Subjects :
- Animals
Humans
Mice
Female
Mice, Inbred BALB C
Antibiotics, Antineoplastic chemistry
Antibiotics, Antineoplastic pharmacology
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Cell Proliferation drug effects
Drug Liberation
Drug Carriers chemistry
Drug Screening Assays, Antitumor
Particle Size
Dendrimers chemistry
Gold chemistry
Doxorubicin chemistry
Doxorubicin pharmacology
Metal Nanoparticles chemistry
Tomography, X-Ray Computed
Subjects
Details
- Language :
- English
- ISSN :
- 2050-7518
- Volume :
- 12
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- Journal of materials chemistry. B
- Publication Type :
- Academic Journal
- Accession number :
- 39301737
- Full Text :
- https://doi.org/10.1039/d4tb01747a