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

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-kappa B). 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.

Automated summary

Precision nanomedicine can effectively and safely induce targeted antitumor responses, overcoming challenges associated with traditional treatment approaches. In this study, a therapeutic nanocomposite was formulated using a hyaluronic acid-coated gold nanoframework (AuNF) delivery system loaded with IT848, a small molecule with potent anti-lymphoma and -myeloma properties. The research demonstrated that the HA-AuNF-formulated IT848 showed superior efficacy in lymphoma mouse models compared to free IT848, confirming the potential of the AuNF system for targeted cancer therapy.