Alsevirone-NF Reduces Serum Testosterone and Inhibits Prostate Cancer Xenograft Growth in Balb/c Nude Mice

Pokrovsky, Vadim S.; Zolottsev, Vladimir A.; Latysheva, Alexandra S.; Kudinov, Vasiliy A.; Anisimova, Natalia; Алманза, Р.Л. М.; Alekseeva, Olga Yu; Baskaev, K. K.; Smirnova, G. P.; Borisova, Yulia A.; Ipatova, O. M.

doi:10.2174/2212697x07999200511082225

Cited by 1 publication

(1 citation statement)

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“…The findings fairly matched the earlier reports by Fernanda da Luz Efe. 2019, and Pokrovsky et al 2020 (Pokrovsky et al 2020;Wang et al 2019). The investigation suggests that PSMA binding and inhibition of androgen production had predominant role in the cellular internalization and cellular function mediated through Apt-ABR-NP.…”

Section: In Vitro Cytotoxicity Assaymentioning

confidence: 98%

ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation

Al Hoque,

Dutta,

Paul

et al. 2023

Cancer Nano

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Prostate cancer (PCa) is one of the fatal illnesses among males globally. PCa-treatment does not include radiotherapy. Chemotherapy eventually causes drug resistance, disease recurrence, metastatic advancement, multi-organ failure, and death. Preclinical data on PCa-induced by carcinogens are truly scarce. Although some data on xenograft-PCa in animals are available, they mostly belonged to immuno-compromised animals. Here, we developed ΔPSap4#5 aptamer surface-functionalized abiraterone-loaded biodegradable nanoparticle (Apt-ABR-NP) to investigate its targeting ability to prostate-specific membrane antigen (PSMA) in carcinogen-induced PCa mice and the therapeutic efficacy of the formulation. Aptamers are called synthetic monoclonal antibodies for their target specificity. However, they are devoid of the toxicity problem generally associated with the antibody. Abiraterone is a testosterone and androgen inhibitor, a new drug molecule that shows good therapeutic efficacy in PCa. The developed nanoparticles were physicochemically characterized and used for various in vitro and in vivo investigations. Nanoparticles had an average size of 149 nm with sustained drug release that followed Korsmeyer–Peppas kinetics. In vitro investigation showed that Apt-ABR-NP produced 87.4% apoptotic cells and 95.3% loss of mitochondrial membrane potential in LNCaP cells after 48 h of incubation. In vivo gamma scintigraphy, live imaging, and biodistribution studies in prostate cancer animal models showed the predominant targeting potential of Apt-ABR-NP. Histopathological investigation showed the remarkable therapeutic efficacy of the formulation. The pharmacokinetic study showed an increased biological half-life and enhanced blood residence time of Apt-ABR-NP. Apt-ABR-NP therapy can thus minimize off-target cytotoxicity, reduce drug loss due to site-specific delivery, and deliver abiraterone in a sustained manner to the organ of interest. Thus, the present study brings new hope for better therapeutic management of PCa in the near future. Graphical Abstract

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Section: In Vitro Cytotoxicity Assaymentioning

confidence: 98%