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Prostate-Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer.
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.
Afiliação
  • Meher N; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Ashley GW; National Institute of Pharmaceutical Education and Research, Raebareli, Lucknow, UP, 226002, India.
  • Bobba KN; ProLynx Inc., San Francisco, CA, 94158, USA.
  • Wadhwa A; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Bidkar AP; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Dasari C; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Mu C; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 94143-0981, USA.
  • Sankaranarayanan RA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Serrano JAC; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Raveendran A; Division of Vascular and Endovascular Surgery, University of California, San Francisco, CA, 94143-0957, USA.
  • Bulkley DP; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Aggarwal R; Department of Pathology, University of California, San Francisco, CA, 94143, USA.
  • Greenland NY; Division of Vascular and Endovascular Surgery, University of California, San Francisco, CA, 94143-0957, USA.
  • Oskowitz A; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158-2517, USA.
  • Wilson DM; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 94143-0981, USA.
  • Seo Y; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Santi DV; Division of Vascular and Endovascular Surgery, University of California, San Francisco, CA, 94143-0957, USA.
  • VanBrocklin HF; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA.
  • Flavell RR; Division of Vascular and Endovascular Surgery, University of California, San Francisco, CA, 94143-0957, USA.
Adv Healthc Mater ; 13(19): e2304618, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38700450
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polietilenoglicóis / Neoplasias da Próstata / Tomografia Computadorizada de Emissão de Fóton Único / Glutamato Carboxipeptidase II Limite: Animals / Humans / Male Idioma: En Revista: Adv Healthc Mater Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polietilenoglicóis / Neoplasias da Próstata / Tomografia Computadorizada de Emissão de Fóton Único / Glutamato Carboxipeptidase II Limite: Animals / Humans / Male Idioma: En Revista: Adv Healthc Mater Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos