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. 2024 Nov:375:438-453.
doi: 10.1016/j.jconrel.2024.09.014. Epub 2024 Sep 19.

Combination non-targeted and sGRP78-targeted nanoparticle drug delivery outperforms either component to treat metastatic ovarian cancer

Jenna N Sjoerdsma  1 , Emily K Bromley  1 , Jaeho Shin  1 , Tyvette Hilliard  2 , Yueying Liu  2 , Caitlin Horgan  3 , Gyoyeon Hwang  1 , Michael Bektas  2 , David Omstead  4 , Tanyel Kiziltepe  1 , M Sharon Stack  5 , Basar Bilgicer  6
Affiliations

Combination non-targeted and sGRP78-targeted nanoparticle drug delivery outperforms either component to treat metastatic ovarian cancer

Jenna N Sjoerdsma et al. J Control Release. 2024 Nov.

Abstract

Metastatic ovarian cancer (MOC) is highly deadly, due in part to the limited efficacy of standard-of-care chemotherapies to metastatic tumors and non-adherent cancer cells. Here, we demonstrated the effectiveness of a combination therapy of GRP78-targeted (TNPGRP78pep) and non-targeted (NP) nanoparticles to deliver a novel DM1-prodrug to MOC in a syngeneic mouse model. Cell surface-GRP78 is overexpressed in MOC, making GRP78 an optimal target for selective delivery of nanoparticles to MOC. The NP + TNPGRP78pep combination treatment reduced tumor burden by 15-fold, compared to untreated control. Increased T cell and macrophage levels in treated groups also suggested antitumor immune system involvement. The NP and TNPGRP78pep components functioned synergistically through two proposed mechanisms of action. The TNPGRP78pep targeted non-adherent cancer cells in the peritoneal cavity, preventing the formation of new solid tumors, while the NP passively targeted existing solid tumor sites, providing a sustained release of the drug to the tumor microenvironment.

Keywords: Antitumor immune response; Lipid nanoparticle; Metastasis; Ovarian cancer; Targeted drug delivery; women's health.

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Conflict of interest statement

Declaration of competing interest Patent application is pending.

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