Prostate‐Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer

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Abstract: The tumor uptake of large non‐targeted nanocarriers primarily occurs through passive extravasation, known as the enhanced permeability and retention (EPR) effect. Prior studies demonstrated improved tumor uptake and retention of 4‐arm 40 kDa star polyethylene glycol (StarPEG) polymers for cancer imaging by adding prostate‐specific membrane antigen (PSMA) targeting small molecule ligands. To test PSMA‐targeted delivery and therapeutic efficacy, StarPEG nanodrugs with/without three copies of PSMA‐targeting ligands, ACUPA, are designed and synthesized. For single‐photon emission computed tomography (SPECT) imaging and therapy, each nanocarrier is labeled with 177Lu using DOTA radiometal chelator. The radiolabeled nanodrugs, [177Lu]PEG‐(DOTA) 1 and [177Lu]PEG‐(DOTA) 1 (ACUPA) 3, are evaluated in vitro and in vivo using PSMA+ PC3‐Pip and/or PSMA– PC3‐Flu cell lines, subcutaneous xenografts and disseminated metastatic models. The nanocarriers are efficiently radiolabeled with 177Lu with molar activities 10.8–15.8 MBq/nmol. Besides excellent in vitro PSMA binding affinity (kD = 51.7 nM), the targeted nanocarrier, [177Lu]PEG‐(DOTA) 1 (ACUPA) 3, demonstrated excellent in vivo SPECT imaging contrast with 21.3% ID/g PC3‐Pip tumors uptake at 192 h. Single doses of 18.5 MBq [177Lu]PEG‐(DOTA) 1 (ACUPA) 3 showed complete resolution of the PC3‐Pip xenografts observed up to 138 days. Along with PSMA‐targeted excellent imaging contrast, these results demonstrated high treatment efficacy of [177Lu]PEG‐(DOTA) 1 (ACUPA) 3 for prostate cancer, with potential for clinical translation.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Prostate‐Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer ; day:17 ; month:05 ; year:2024 ; extent:15
Advanced healthcare materials ; (17.05.2024) (gesamt 15)

Creator
Meher, Niranjan
Ashley, Gary W.
Bobba, Kondapa Naidu
Wadhwa, Anju
Bidkar, Anil P.
Dasari, Chandrashekhar
Mu, Changhua
Sankaranarayanan, Ramya Ambur
Serrano, Juan A. Camara
Raveendran, Athira
Bulkley, David P.
Aggarwal, Rahul
Greenland, Nancy Y.
Oskowitz, Adam
Wilson, David M.
Seo, Youngho
Santi, Daniel V.
VanBrocklin, Henry F.
Flavell, Robert R.

DOI
10.1002/adhm.202304618
URN
urn:nbn:de:101:1-2405171435362.846005310905
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:48 AM CEST

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Associated

  • Meher, Niranjan
  • Ashley, Gary W.
  • Bobba, Kondapa Naidu
  • Wadhwa, Anju
  • Bidkar, Anil P.
  • Dasari, Chandrashekhar
  • Mu, Changhua
  • Sankaranarayanan, Ramya Ambur
  • Serrano, Juan A. Camara
  • Raveendran, Athira
  • Bulkley, David P.
  • Aggarwal, Rahul
  • Greenland, Nancy Y.
  • Oskowitz, Adam
  • Wilson, David M.
  • Seo, Youngho
  • Santi, Daniel V.
  • VanBrocklin, Henry F.
  • Flavell, Robert R.

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