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Functionalized nanoparticles targeting biomarkers for prostate cancer imaging and therapy.

ABSTRACT: Nanomedicine is an evolving field of scientific research with unique advantages and challenges for the detection and treatment of medical diseases. Since 1995, the FDA has approved the administration of nanoparticle-based therapies. The initial generation of nanoparticles relied on an enhanced permeability and retention effect, associated with an increased penetrability of tumor related blood vessels. With increasing knowledge of biomarkers and molecular targets, active targeting of circulating tumor cells by nanoparticles provides an exciting area for application. The selective targeting of prostate cancer cells using a nanotechnology-based mechanism has the potential to optimize the delivery of therapeutic payloads directly to prostate cancer cells while minimizing systemic toxicities. The molecular targets that have been studied include prostate specific membrane antigen, gastrin-releasing peptide protein, glucose related protein, CD44, claudin, C-X-C chemokine receptor type 4 (CXCR-4), and adenosine. The clinical potential for nanoparticle-based therapies is supported by several studies that have progressed past the preclinical stage into clinical trials. In this review, we present the molecular biomarkers that have been targeted by ligands conjugated to the surface of nanoparticles for prostate cancer imaging and therapy.

SUBMITTER: Choksi AU

PROVIDER: S-EPMC9301064 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeSilver nanoparticles (AgNPs) have shown great potential as anticancer agents, namely in therapies' resistant forms of cancer. The progression of prostate cancer (PCa) to resistant forms of the disease (castration-resistant PCa, CRPC) is associated with poor prognosis and life quality, with current limited therapeutic options. CRPC is characterized by a high glucose consumption, which poses as an opportunity to direct AgNPs to these cancer cells. Thus, this study explores the effect of glucose functionalization of AgNPs in PCa and CRPC cell lines (LNCaP, Du-145 and PC-3).MethodsAgNPs were synthesized, further functionalized, and their physical and chemical composition was characterized both in water and in culture medium, through UV-visible spectrum, dynamic light scattering (DLS), transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR). Their effect was assessed in the cell lines regarding AgNPs' entering pathway, cellular proliferation capacity, ROS production, mitochondrial membrane depolarization, cell cycle analysis and apoptosis evaluation.ResultsAgNPs displayed an average size of 61nm and moderate monodispersity with a slight increase after functionalization, and a round shape. These characteristics remained stable when redispersed in culture medium. Both AgNPs and G-AgNPs were cytotoxic only to CRPC cells and not to hormone-sensitive ones and their effect was higher after functionalization showing the potential of glucose to favor AgNPs' uptake by cancer cells. Entering through endocytosis and being encapsulated in lysosomes, the NPs increased the ROS, inducing mitochondrial damage, and arresting cell cycle in S Phase, therefore blocking proliferation, and inducing apoptosis.ConclusionThe nanoparticles synthesized in the present study revealed good characteristics and stability for administration to cancer cells. Their uptake through endocytosis leads to promising cytotoxic effects towards CRPC cells, revealing the potential of G-AgNPs as a future therapeutic approach to improve the management of patients with PCa resistant to hormone therapy or metastatic disease.

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Functionalized nanoparticles targeting biomarkers for prostate cancer imaging and therapy.

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