Cross-linking Poly(caprolactone)–Polyamidoamine Linear Dendritic Block Copolymers for Theranostic Nanomedicine

Authors

Indika Chandrasiri, University of MississippiFollow
Mahesh Loku Yaddehige, University of MississippiFollow
Bo Li, Southern Methodist UniversityFollow
Yuzhe Sun, Auburn University
William E. Meador, University of MississippiFollow
Austin Dorris, University of Mississippi
Mohammad Farid Zia, University of Southern MississippiFollow
Nathan I. Hammer, University of MississippiFollow
Alex Flynt, University of Southern MississippiFollow
Jared H. Delcamp, University of MississippiFollow
Edward Davis, Auburn UniversityFollow
Alexander Lippert, Southern Methodist University

Document Type

Article

Publication Date

1-6-2022

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

Abstract

This study represents a comparative analysis of the solution behavior and self-assembly pattern of two linear dendritic block copolymers (LDBCs) composed of a generation 3 polyamidoamine (PAMAM) dendron as the dendritic block and poly(caprolactone) (PCL) as the linear block, the latter of which is modified with pendant phenyl groups. Phenyl substituents were introduced to induce physical cross-linking in LDBC nanoparticles via π–π stacking. A synthetic strategy was developed to access phenyl substituted LDBCs through an ε-caprolactone monomer derivative followed by ring-opening polymerization to form a library of LDBCs with yields above 83%. Polymersome-like nanoparticles were observed in water with a 74.4 nm average diameter. Cross-linked LDBC nanoparticles demonstrated a 37.1% relative decrease in the critical aggregation concentration (CAC) and a 27.3–41.2% relative increase of hydrophobic loading efficiency relative to unsubstituted LDBCs. Nanoparticles loaded with a potential photothermal agent (phenyl indolizine-C5 (C5)) showed a photothermal efficiency of 49.4% with a heating temperature of 44.4 °C. These nanoparticles were efficiently loaded into HEK293 cells with cell viability above 87.5% at the highest concentration. Upon illumination with red light, nanoparticles loaded with photothermal agent were able to induce cell death in cancer cells. This work suggests that the phenyl substituted LDBCs form nanoparticles with enhanced stability and loading efficiencies compared to conventional nonphenylated systems and display a greater potential to be used as nanocarriers in theranostic nanomedicine.

Publication Title

ACS Applied Polymer Materials

Volume

4

Issue

5

First Page

2972

Last Page

2986

Recommended Citation

Chandrasiri, I., Yaddehige, M. L., Li, B., Sun, Y., Meador, W. E., Dorris, A., Zia, M. F., Hammer, N. I., Flynt, A., Delcamp, J. H., Davis, E., Lippert, A. (2022). Cross-linking Poly(caprolactone)–Polyamidoamine Linear Dendritic Block Copolymers for Theranostic Nanomedicine. ACS Applied Polymer Materials, 4(5), 2972-2986.
Available at: https://aquila.usm.edu/fac_pubs/19886