TY - JOUR
T1 - Targeted Lymphoma Therapy Using a Gold Nanoframework-Based Drug Delivery System
AU - Bariana, Manpreet
AU - Zhang, Beilu
AU - Sun, Jingyu
AU - Wang, Weiwei
AU - Wang, Jinping
AU - Cassella, Elena
AU - Myint, Faith
AU - Anuncio, Shaina A.
AU - Ouk, Samedy
AU - Liou, Hsiou Chi
AU - Tan, Ming
AU - Wang, Hongjun
AU - Zakrzewski, Johannes L.
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/2/8
Y1 - 2023/2/8
N2 - 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.
AB - 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.
KW - CD44
KW - gold nanoparticles
KW - hyaluronic acid
KW - lymphoma
KW - nuclear factor-κB inhibitor
KW - targeted drug delivery
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U2 - 10.1021/acsami.2c17214
DO - 10.1021/acsami.2c17214
M3 - Article
C2 - 36701696
AN - SCOPUS:85147160522
SN - 1944-8244
VL - 15
SP - 6312
EP - 6325
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 5
ER -