Hybrid Nanoparticle System Integrating Tumor-Derived Exosomes and Poly(amidoamine) Dendrimers: Implications for an Effective Gene Delivery Platform

Ashita Nair, Kaila Javius-Jones, Jason Bugno, Michael J. Poellmann, Narsimha Mamidi, In San Kim, Ick Chan Kwon, Heejoo Hong, Seungpyo Hong

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Nanoscale drug delivery systems for cancer treatment have demonstrated promising results in enhancing the selectivity of therapeutic agents while reducing their toxic side effects. However, several biological and physical barriers, such as the immunogenicity and undesirable biodistributions of such delivery systems, have hindered their fast translation. To address these issues, we have developed an exosome-dendrimer hybrid nanoparticle (NP) platform to combine the advantageous biological properties of natural exosomes and synthetic dendrimers into a single NP system. The novel hybrid NPs, consisting of exosomes derived from MCF7 cells and functionalized poly(amidoamine) (PAMAM) dendrimers, were prepared using sonication and characterized in terms of loading efficiency, size, cytotoxicity, and cellular interactions. Our results indicate that the loading of dendrimers into exosomes is dependent on dendrimer size and charge. The hybrid NPs inherited the size (∼150 nm), surface charge (−10 mV), and surface protein markers (CD81 and CD63) of exosomes. Importantly, the hybrid NPs enhanced the cellular internalization of amine-terminated PAMAM dendrimers (p < 0.05) while exhibiting substantially lower cytotoxicity than the free positively charged dendrimers (113.3 vs 35.6% of cell viability at 500 nM, p < 0.05). These advantageous properties of hybrid NPs were leveraged for use as a gene delivery vehicle, resulting in enhanced oligonucleotide delivery (over 2-fold) to cancer cells, compared to dendrimers alone. Furthermore, the hybrid NPs effectively delivered small interfering RNA (siRNA) as well, downregulating programmed death-ligand 1 (PD-L1) expression significantly more (3.8-fold) than dendrimers alone (p < 0.05). Our results demonstrate that the individual characteristics of both exosomes and dendrimers can be integrated to generate a multifaceted NP platform, proposing a novel NP design strategy.

Original languageEnglish
Pages (from-to)3138-3150
Number of pages13
JournalChemistry of Materials
Volume35
Issue number8
DOIs
Publication statusPublished - 2023 Apr 25
Externally publishedYes

Bibliographical note

Funding Information:
This study was partially supported by National Science Foundation (NSF) under grants # DMR-1741560 and 1808251 and Milton J Henrichs Chair Fund.

Publisher Copyright:
© 2023 American Chemical Society.

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering
  • Materials Chemistry

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