journal article·2023-02-08Open access

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

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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: RNA Interference and Gene Delivery · Immunotherapy and Immune Responses · Multiple Myeloma Research and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey 07110, United States

Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States

Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07303, United States

ImmuneTarget Inc., San Diego, California 92121, United States

Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University, Washington, District of Columbia 20057, United States

Center for Healthcare Innovation, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States

Department of Oncology, Georgetown University, Washington, District of Columbia 20057, United States

Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

Funding

National Cancer Institute · International Myeloma Society · Children?s Leukemia Research Association · National Institute of Arthritis and Musculoskeletal and Skin Diseases · American Society of Hematology · HMH Foundation · HMH MSK Immunology Collaboration · Tackle Kids Cancer · Hackensack Meridian School of Medicine

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