Endogenous Targeting of Lipid Nanoparticles to Kidney Tumors
Although the delivery of genetic therapies to tumors using nanoparticles remains challenging, targeting may be enabled via plasma membrane receptors overexpressed on certain cancer cells. Here, we developed an endogenous targeting strategy for trafficking intravenously administered mRNA (and siRNA) lipid nanoparticles (LNPs) to clear cell renal cell carcinoma (ccRCC) kidney tumors. LNPs were engineered to adsorb circulating plasma vitronectin (Vtn), the ligand for α<sub>V</sub>β<sub>3</sub> integrin/vitronectin receptor (Vtn-R), which is overexpressed in ccRCC. Functional mRNA delivery to human ccRCC cells was enhanced 952-fold <i>in vitro</i> and 42-fold in patient-derived ccRCC tumor fragments orthotopically transplanted in mice. This proof-of-concept study represents a new direction in the cancer nanomedicine field by modulating the physicochemical properties of LNPs to achieve <i>in situ</i> ligand binding and tumor targeting.
Authors
- Sean A. Dilliard (ORCID: https://orcid.org/0000-0002-5884-8392)
- Daniel J. Siegwart (ORCID: https://orcid.org/0000-0003-3823-1931)
- Vanina Toffessi Tcheuyap (ORCID: https://orcid.org/0000-0002-6817-9241)
- Ramesh Butti (ORCID: https://orcid.org/0000-0002-6011-7791)
- Amogh Vaidya (ORCID: https://orcid.org/0000-0003-0712-659X)
- Jeffrey Miyata (ORCID: https://orcid.org/0000-0001-8278-3026)
- Gopinath Prakasam (ORCID: https://orcid.org/0000-0003-1839-7969)
- Yun‐Chieh Sung (ORCID: https://orcid.org/0000-0001-7525-0694)
- James Brugarolas (ORCID: https://orcid.org/0000-0002-8575-499X)
- Yufen Xiao (ORCID: https://orcid.org/0000-0002-5604-7479)
- Priyanka Patel (ORCID: https://orcid.org/0009-0009-1953-7709)
- Payal Kapur (ORCID: https://orcid.org/0000-0002-4239-0495)
- Arijit Mal (ORCID: https://orcid.org/0000-0002-3960-2805)
- Stephen D. Moore (ORCID: https://orcid.org/0000-0002-4207-7941)
- Sumanta Chatterjee (ORCID: https://orcid.org/0000-0002-6832-0073)
- Julien Santelli (ORCID: https://orcid.org/0000-0001-5546-5831)
- Erick Guerrero (ORCID: https://orcid.org/0000-0002-2076-3537)
- Jing Liu (ORCID: https://orcid.org/0000-0002-5281-9769)
- Cheng Cheng Zhang (ORCID: https://orcid.org/0000-0003-4763-3887)
- Eunwoo Song (ORCID: https://orcid.org/0000-0003-0642-7083)
Institutions
- Simmons University (US)
- Maryland Oncology Hematology (US)
- Genetic Resources Center (JP)
- Palmetto Hematology Oncology (US)
- Hematology Oncology Associates (US)
- Harold C. Simmons Comprehensive Cancer Center
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- ACS Nano
- Published
- 2025-08-20
- DOI
- https://doi.org/10.1021/acsnano.5c05370
- Citations
- 3
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 1.79
Funders
- Welch Foundation
- National Cancer Institute
- National Institute of Biomedical Imaging and Bioengineering
- Congressionally Directed Medical Research Programs