Synthesis and Preliminary Biological Assessment of Carborane-Loaded Theranostic Nanoparticles to Target Prostate-Specific Membrane Antigen.

Autor: Meher N; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States., Seo K; Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143, United States., Wang S; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States., Bidkar AP; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States., Fogarty M; Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143, United States., Dhrona S; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States., Huang X; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94158, United States., Tang R; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States., Blaha C; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94158, United States., Evans MJ; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143-0981, United States.; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California 94158-2517, United States., Raleigh DR; Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143, United States.; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California 94143, United States., Jun YW; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143-0981, United States.; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California 94158-2517, United States.; Department of Otolaryngology, University of California, San Francisco, San Francisco, California 94158, United States., VanBrocklin HF; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143-0981, United States., Desai TA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94158, United States., Wilson DM; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143-0981, United States., Ozawa T; Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143, United States., Flavell RR; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143, United States.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143-0981, United States.; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California 94158-2517, United States.
Jazyk: angličtina
Zdroj: ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2021 Nov 24; Vol. 13 (46), pp. 54739-54752. Date of Electronic Publication: 2021 Nov 09.
DOI: 10.1021/acsami.1c16383
Abstrakt: Boron neutron capture therapy (BNCT) is an encouraging therapeutic modality for cancer treatment. Prostate-specific membrane antigen (PSMA) is a cell membrane protein that is abundantly overexpressed in prostate cancer and can be targeted with radioligand therapies to stimulate clinical responses in patients. In principle, a spatially targeted neutron beam together with specifically targeted PSMA ligands could enable prostate cancer-targeted BNCT. Thus, we developed and tested PSMA-targeted poly(lactide- co -glycolide)-block-poly(ethylene glycol) (PLGA- b -PEG) nanoparticles (NPs) loaded with carborane and tethered to the radiometal chelator deferoxamine B (DFB) for simultaneous positron emission tomography (PET) imaging and selective delivery of boron to prostate cancer. Monomeric PLGA- b -PEGs were covalently functionalized with either DFB or the PSMA ligand ACUPA. Different nanoparticle formulations were generated by nanoemulsification of the corresponding unmodified and DFB- or ACUPA-modified monomers in varying percent fractions. The nanoparticles were efficiently labeled with 89 Zr and were subjected to in vitro and in vivo evaluation. The optimized DFB(25)ACUPA(75) NPs exhibited strong in vitro binding to PSMA in direct binding and competition radioligand binding assays in PSMA(+) PC3-Pip cells. [ 89 Zr]DFB(25) NPs and [ 89 Zr]DFB(25)ACUPA(75) NPs were injected to mice with bilateral PSMA(-) PC3-Flu and PSMA(+) PC3-Pip dual xenografts. The NPs demonstrated twofold superior accumulation in PC3-Pip tumors to that of PC3-Flu tumors with a tumor/blood ratio of 25; however, no substantial effect of the ACUPA ligands was detected. Moreover, fast release of carborane from the NPs was observed, resulting in a low boron delivery to tumors in vivo . In summary, these data demonstrate the synthesis, characterization, and initial biological assessment of PSMA-targeted, carborane-loaded PLGA- b -PEG nanoparticles and establish the foundation for future efforts to enable their best use in vivo .
Databáze: MEDLINE
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