Prostate cancer (PCa) accounts for a high number of deaths in males with no available curative treatments. Patients with PCa are commonly diagnosed in advanced stages due to the lack of symptoms in the early stages. Recently, the research focus was directed toward gene editing in cancer therapy. Small interfering RNA (siRNA) intervention is considered as a powerful tool for gene silencing (knockdown), enabling the suppression of oncogene factors in cancer. This strategy is applied to the treatment of various cancers including PCa. The siRNA can inhibit proliferation and invasion of PCa cells and is able to promote the anti-tumor activity of chemotherapeutic agents. However, the off-target effects of siRNA therapy remarkably reduce its efficacy in PCa therapy. To date, various carriers were designed to improve the delivery of siRNA and, among them, nanoparticles are of importance. Nanoparticles enable the targeted delivery of siRNAs and enhance their potential in the downregulation of target genes of interest. Additionally, nanoparticles can provide a platform for the co-delivery of siRNAs and anti-tumor drugs, resulting in decreased growth and migration of PCa cells. The efficacy, specificity, and delivery of siRNAs are comprehensively discussed in this review to direct further studies toward using siRNAs and their nanoscale-delivery systems in PCa therapy and perhaps other cancer types.

The development of novel magnetic nanoparticles (MNPs) with satisfactory biocompatibility for biomedical applications has been the subject of extensive exploration over the past two decades. In this work, we synthesized superparamagnetic iron oxide MNPs coated with polystyrene sulfonic acid (PSS-MNPs) and with a conventional co-precipitation method. The core size and hydrodynamic diameter of the PSS-MNPs were determined as 8–18 nm and 50–200 nm with a transmission electron microscopy and dynamic light scattering, respectively. The saturation magnetization of the particles was measured as 60 emu g⁻¹ with a superconducting quantum-interference-device magnetometer. The PSS content in the PSS-MNPs was 17 % of the entire PSS-MNPs according to thermogravimetric analysis. Fourier-transform infrared spectra were recorded to detect the presence of SO₃ ⁻ groups, which confirmed a successful PSS coating. The structural properties of the PSS-MNPs, including the crystalline lattice, composition and phases, were characterized with an X-ray powder diffractometer and 3D nanometer-scale Raman microspectrometer. MTT assay and Prussian-blue staining showed that, although PSS-MNPs caused no cytotoxicity in both NIH-3T3 mouse fibroblasts and SK-HEP1 human liver-cancer cells up to 1000 μg mL⁻¹, SK-HEP1 cells exhibited significantly greater uptake of PSS-MNPs than NIH-3T3 cells. The low cytotoxicity and high biocompatibility of PSS-MNPs in human cancer cells demonstrated in the present work might have prospective applications for drug delivery.

Hormone-refractory prostate cancer frequently relapses from therapy and inevitably progresses to a bone-metastatic status with no cure. Understanding of the molecular mechanisms conferring resistance to androgen deprivation therapy has the potential to lead to the discovery of novel therapeutic targets for type of prostate cancer with poor prognosis. Progression to castration-resistant prostate cancer (CRPC) is characterized by aberrant androgen receptor (AR) expression and persistent AR signaling activity. Alterations in metabolic activity regulated by oncogenic pathways, such as c-Myc, were found to promote prostate cancer growth during the development of CRPC. Non-coding RNAs represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer and various other cancers by their hyperactivity or diminished function. A number of studies have examined differentially expressed non-coding RNAs in each stage of prostate cancer. Herein, we highlight the emerging impacts of microRNAs and long non-coding RNAs linked to reactivation of the AR signaling axis and reprogramming of the cellular metabolism in prostate cancer. The translational implications of non-coding RNA research for developing new biomarkers and therapeutic strategies for CRPC are also discussed.

Mesenchymal stem cells (MSCs) that display homing and infiltration properties towards tumor cells are a promising cellular targeting vector for brain tumor therapy but are limited to local-regional delivery in current preclinical models. Here, we investigated whether placenta-derived MSCs (P-MSCs) are a superior cellular vector for systemic targeting of glioblastoma stem-like cells (GSCs), with an imaging modality to real-time monitor the trafficking P-MSCs to glioblastoma sites. Results demonstrated that P-MSCs had greater migratory activity towards GSCs and across blood–brain barrier compared with bone marrow-derived MSCs, and this activity was enhanced by hypoxia precondition. Chemokine ligand 5 was identified as a chemoattractant responsible for the glioblastoma tropism of P-MSCs. Polyethylene glycol-coated superparamagnetic iron oxide (PEG–SPIO) was synthesized for cellular labelling and imaging P-MSCs, displaying high cellular uptake and no cytotoxic effect on P-MSCs cell proliferation or stemness property. The homing effects of intravenously administered PEG–SPIO-labelled P-MSCs towards intracerebral GSCs were able to be detected in mice models through T2-weighted magnetic resonance imaging (MRI). This study suggests the possibility of innovative systemic P-MSC-based cell therapy for aggressive GSCs, developing a state-of-the-art theranostic technique for real-time tracking of therapeutic P-MSCs tumor infiltration through cellular MRI.

Human beta-defensin-1 (hBD-1) is one of a number of small cationic host-defense peptides. Besides its well-known broad-spectrum antimicrobial function, hBD-1 has recently been identified as a chromosome 8p tumor-suppressor gene. The role of hBD-1 in modulating the host immune response to oncogenesis, associated with cell signaling and potential therapeutic applications, has become increasingly appreciated over time. In this study, multiple approaches were used to illustrate hBD-1 anti-tumor activities. Results demonstrate that hBD-1 peptide alters human epidermal growth factor receptor 2 (HER2) signal transduction and represses retroviral-mediated transgene expression in cancer cells. Loss of orthologous murine defense-1 (mBD1) in mice enhances nickel sulfate-induced leiomyosarcoma and causes mouse kidney cells to exhibit increased susceptibility to HPV-16 E6/7-induced neoplastic transformation. Furthermore, for the first time, a novel function of the urine-derived hBD-1 peptide was discovered to suppress bladder cancer growth and this may lead to future applications in the treatment of malignancy.

The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in prostate cancer and its application in targeted gene therapy have not been investigated. Herein, we demonstrated that the L1CAM was expressed in androgen-insensitive and highly metastatic human prostate cancer cell lines. The correlation between L1CAM expression and prostate cancer metastasis was also validated in serum samples of prostate cancer patients. Knockdown of L1CAM expression in prostate cancer cells by RNA interference significantly decreased their aggressive behaviors, including colony formation, migration and invasion in vitro, and tumor formation in a metastatic murine model. These anti-malignant phenotypes of L1CAM-knockdown cancer cells were accompanied by G0/G1 cell cycle arrest and suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression and nuclear factor NF-κB activation. In vivo targeting of L1CAM expression using liposome-encapsulated L1CAM siRNAs effectively inhibited prostate cancer growth in mouse bone, which was associated with decreased L1CAM expression and cell proliferation by tumor cells. These results provide the first evidence for L1CAM being a major contributor to prostate cancer metastasis and translational application of siRNA-based L1CAM-targeted therapy.