MiR-197 Inhibitor Loaded AbCD133@MSNs@GNR Affects the Development of Prostate Cancer Through Targeting ITGAV

Abstract

Prostate cancer is one of the most severe male malignant tumors, which ranks second in mortality rate among all tumors. Traditional methods of treatment for prostate cancer produce obvious side effects and a high recurrence rate. Cancer stem cells are considered to be a group of cells that determine the proliferation, metastasis, and drug resistance of tumor. Prostate cancer therapy based on microRNAs and prostate cancer stem cells (PCSCs) has been a research hot spot in this field. Previous studies have reported that miR-197 plays an important role in the occurrence and development of prostate cancer, but the molecular mechanism of miR-197 on the development of prostate cancer has not been reported yet. In this study, we verified that miR-197 is significantly overexpressed in prostate cancer tissues and prostate cancer cells. Then, we verified that miR-197 expression affects the proliferation, invasion, and metastasis of prostate cancer cells by regulating integrin subunit alpha V (ITGAV) expression through STAT5 pathway, and the results indicated that the miR-197 inhibitor can be a prostate cancer suppressor. Then we synthesized the AbCD133@GNR@MSNs@miR-197 inhibitor drug carrier, in which 35.42 μg of the miR-197 inhibitor could be loaded in 1 mg of AbCD133@GNR@MSNs. The AbCD133@GNR@MSNs@miR-197 inhibitor demonstrated good photothermal properties and photothermal controlled-release properties. The modified CD133 antibodies on the surface of the nano drug carrier helped more drug carriers to enter the PCSCs. The pharmacodynamic effects of the AbCD133@GNR@MSNs@miR-197 inhibitor on PCSCs in vivo and in vitro were studied under near-infrared radiation. The results showed that the AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could not only significantly suppress the development of PCSCs through ITGAV/STAT5 pathway but also significantly suppress the growth of PCSC solid tumors. In short, our study verified that miR-197 regulates the development of PCSCs through STAT5 pathway by targeting ITGAV, and the AbCD133@MSNs@GNR@miR-197 inhibitor could be a potential suppressor used in prostate cancer treatment. In short, our study found that miR-197 affected the development of prostate cancer by regulating ITGAV. The AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could suppress the development and growth of PCSCs in vitro and in solid tumors not only by targeting the ITGAV but also through photothermal therapy. Our study not only provides a theoretical basis for the clinical treatment of prostate cancer but also provides a research scheme of drug loading and microRNA-based photothermal controlled therapy for prostate cancer.

Gene and Photothermal Combination Therapy: Principle, Materials, and Amplified Anticancer Intervention

“…Adapted with permission. [ 85 ] Copyright 2019, Frontiers Media S.A. c) AFM (left) and TEM (right) images of Bi@PP (upper), and the release profile of Cy5‐siRNA (bottom). Adapted with permission.…”

“…Compared to free ICG molecules, HMM-siRNA NCs exhibited high tumor accumulation at 24 h post-injection and contributed to significant tumor growth suppression via combined low-temperature PTT and Yes1 Associated Transcriptional Regulator (YAP1) siRNA-induced GT. In another study, Ju et al [85] prepared GNR@MSNs core-shell NPs by coating golden nanorods (GNRs) with mesoporous silica and modifying them with CD133 antibodies to target prostate cancer stem cells. The mesoporous AbCD133@GNR@MSNs were sealed with tetradecanol as a phase-changing material (PCM) (Figure 7b).…”

“…b) TEM image of GNR@MSNs (upper), and release of miR197 from AbCD133@GNR@MSNs under different conditions (bottom). Adapted with permission [85]. Copyright 2019, Frontiers Media S.A. c) AFM (left) and TEM (right) images of Bi@PP (upper), and the release profile of Cy5-siRNA (bottom).…”

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1

“…miR-197 and miR-200a-c positively correlated to PD-L1 mRNA levels and were inversely associated with mPD-L1 in a large PC series, suggesting that mPD-L1 was associated with lower mRNA levels destabilizing miR-197 and miR-200a-c [90]. miR-197 expression was rarely investigated in PC: it seems involved in the proliferation, invasion, and metastatic potential of PC cells by regulating integrin subunit alpha V (ITGAV) expression through the STAT5 pathway [197]. miR-197-3p is apparently involved in PI3K/AKT3 signaling, possibly favoring castration-resistance by targeting RAS, RHO, and the SCF complex [198].…”

Lipid nanomaterials-based RNA therapy and cancer treatment

“…These therapies have exhibited remarkable clinical efficacy. However, the life quality of patients receiving these traditional therapies is impacted seriously by multiple side effects, such as those from surgical or chemical castration 103 . While prostate cancer can be induced by various risk factors, such as race, age, family history, and geneticity.…”