Targeted Lymphoma Therapy Using a Gold Nanoframework-Based Drug Delivery System

Manpreet Bariana, Beilu Zhang, Jingyu Sun, Weiwei Wang, Jinping Wang, Elena Cassella, Faith Myint, Shaina A. Anuncio, Samedy Ouk, Hsiou Chi Liou, Ming Tan, Hongjun Wang, Johannes L. Zakrzewski

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Precision nanomedicine can be employed as an alternative to chemo- or radiotherapy to overcome challenges associated with the often narrow therapeutic window of traditional treatment approaches, while safely inducing effective, targeted antitumor responses. Herein, we report the formulation of a therapeutic nanocomposite comprising a hyaluronic acid (HA)-coated gold nanoframework (AuNF) delivery system and encapsulated IT848, a small molecule with potent antilymphoma and -myeloma properties that targets the transcriptional activity of nuclear factor kappa B (NF-κB). The porous AuNFs fabricated via a liposome-templated approach were loaded with IT848 and surface-functionalized with HA to formulate the nanotherapeutics that were able to efficiently deliver the payload with high specificity to myeloma and lymphoma cell lines in vitro. In vivo studies characterized biodistribution, pharmacokinetics, and safety of HA-AuNFs, and we demonstrated superior efficacy of HA-AuNF-formulated IT848 vs free IT848 in lymphoma mouse models. Both in vitro and in vivo results affirm that the AuNF system can be adopted for targeted cancer therapy, improving the drug safety profile, and enhancing its efficacy with minimal dosing. HA-AuNF-formulated IT848 therefore has strong potential for clinical translation.

Original languageEnglish
Pages (from-to)6312-6325
Number of pages14
JournalACS Applied Materials and Interfaces
Volume15
Issue number5
DOIs
StatePublished - 8 Feb 2023

Keywords

  • CD44
  • gold nanoparticles
  • hyaluronic acid
  • lymphoma
  • nuclear factor-κB inhibitor
  • targeted drug delivery

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