Self-Assembled
STING-Activating Coordination Nanoparticles
for Cancer Immunotherapy and Vaccine Applications
Posted on 2024-04-03 - 13:09
The
cGAS-STING pathway plays a crucial role in innate immune activation
against cancer and infections, and STING agonists based on cyclic
dinucleotides (CDN) have garnered attention for their potential use
in cancer immunotherapy and vaccines. However, the limited drug-like
properties of CDN necessitate an efficient delivery system to the
immune system. To address these challenges, we developed an immunostimulatory
delivery system for STING agonists. Here, we have examined aqueous
coordination interactions between CDN and metal ions and report that
CDN mixed with Zn2+ and Mn2+ formed distinctive
crystal structures. Further pharmaceutical engineering led to the
development of a functional coordination nanoparticle, termed the
Zinc–Mn–CDN Particle (ZMCP), produced by a simple aqueous
one-pot synthesis. Local or systemic administration of ZMCP exerted
robust antitumor efficacy in mice. Importantly, recombinant protein
antigens from SARS-CoV-2 can be simply loaded during the aqueous one-pot
synthesis. The resulting ZMCP antigens elicited strong cellular and
humoral immune responses that neutralized SARS-CoV-2, highlighting
ZMCP as a self-adjuvant vaccine platform against COVID-19 and other
infectious pathogens. Overall, this work establishes a paradigm for
developing translational coordination nanomedicine based on drug–metal
ion coordination and broadens the applicability of coordination medicine
for the delivery of proteins and other biologics.
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Sun, Xiaoqi; Huang, Xuehui; Park, Kyung Soo; Zhou, Xingwu; Kennedy, Andrew A.; Pretto, Carla D.; et al. (1753). Self-Assembled
STING-Activating Coordination Nanoparticles
for Cancer Immunotherapy and Vaccine Applications. ACS Publications. Collection. https://doi.org/10.1021/acsnano.3c11374