{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:57:43Z","timestamp":1781326663090,"version":"3.54.1"},"reference-count":62,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R21CA245343"],"award-info":[{"award-number":["R21CA245343"]}]},{"name":"Quantitative Bio-Element Analysis and Mapping (QBEAM) Center at Michigan State University","award":["P41GM135018"],"award-info":[{"award-number":["P41GM135018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Normal prostate epithelial cells accumulate high intracellular zinc levels that maintain optimum mitochondrial metabolism and proliferation. Prostate cancer cells lose this zinc-accumulating capacity, enabling metabolic reprogramming that supports tumor progression. Restoring intracellular zinc selectively in prostate tumors represents a promising therapeutic strategy; however, systemic zinc administration is limited by the inability of prostate cancer cells to take up free zinc resulting from ZIP1 transporter downregulation. To overcome this challenge, we developed a formulation of prostate-specific membrane antigen (PSMA)-targeted, zinc-loaded liposomes (Zn-TL) to enable tumor-selective intracellular zinc delivery. Zn-TL was prepared with uniform nanoscale size, low polydispersity, and negative surface charge. The formulation showed minimal zinc leakage during storage and sustained retention in vitro. In prostate cancer cells, Zn-TL demonstrated receptor-mediated uptake, resulting in increased cytotoxicity and apoptosis. In vivo, we performed proof-of-principle studies showing prolonged circulation and tumor accumulation of Zn-TL in mice bearing PSMA-positive tumors. While tumor growth was delayed during early and intermediate stages of tumor development, this effect diminished at later stages. The stage-dependent efficacy suggests that Zn-TL may be most effective when used earlier in disease progression. These results also suggest that Zn-TL represents a promising platform for metabolic intervention and may benefit from combination strategies to enhance efficacy in advanced disease.<\/jats:p>","DOI":"10.3390\/nano16120705","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:43:54Z","timestamp":1780965834000},"page":"705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of PSMA-Targeted Liposomal Zinc for Prostate Cancer Therapy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3241-2504","authenticated-orcid":false,"given":"Sujan Kumar","family":"Mondal","sequence":"first","affiliation":[{"name":"Precision Health Program, Michigan State University, 766 Service Road, East Lansing, MI 48824, USA"},{"name":"Department of Radiology, College of Human Medicine, Michigan State University, 846 Service Road, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kenyon","sequence":"additional","affiliation":[{"name":"Precision Health Program, Michigan State University, 766 Service Road, East Lansing, MI 48824, USA"},{"name":"Department of Radiology, College of Human Medicine, Michigan State University, 846 Service Road, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9061-9971","authenticated-orcid":false,"given":"Alexander L.","family":"Klibanov","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Virginia, Davis Wing, Hospital Drive, Suite 5357, Charlottesville, VA 22904, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-7204","authenticated-orcid":false,"given":"Anna","family":"Moore","sequence":"additional","affiliation":[{"name":"Precision Health Program, Michigan State University, 766 Service Road, East Lansing, MI 48824, USA"},{"name":"Department of Radiology, College of Human Medicine, Michigan State University, 846 Service Road, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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