A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growth<i>in vivo</i>

Yanjun, Diao; Liu, Jiayun; Ma, Yue; Su, Ming-quan; Zhang, Hongyi; Hao, Xiaoke

doi:10.1080/15384047.2016.1156266

Cited by 23 publications

(11 citation statements)

References 43 publications

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“…Targeting ligands, aptamers and antibodies coupled to nucleotides not only shield miR-interfering drugs from fast renal clearance, but also allow targeting of specific cell types. Thus, hapten-binding bi-specific antibodies were shown to facilitate the knockdown of the target gene by delivering haptenylated siRNA complexed with dynamic polyconjugates (180)(181)(182)(183)(184)(185)(186)(187)(188)(189)(190). Upon internalization, release of RNA can be facilitated by conjugates coupled via acid-sensitive or protease cleavable linkers within the acidic endosome (191,192).…”

Section: Therapeutic Aspectsmentioning

confidence: 99%

The Functional Role of Prostate Cancer Metastasis-related Micro-RNAs

Weidle

Epp

Birzele

et al. 2018

Cancer Genomics Proteomics

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The mortality of patients with hormone-resistant prostate cancer can be ascribed to a large degree to metastasis to distant organs, predominantly to the bones. In this review, we discuss the contribution of micro-RNAs (miRs) to the metastatic process of prostate cancer. The criteria for selection of miRs for this review were the availability of preclinical in vivo metastasis-related data in conjunction with prognostic clinical data. Depending on their function in the metastatic process, the corresponding miRs are up-or downregulated in prostate cancer tissues when compared to matching normal tissues. Up-regulated miRs preferentially target suppressors of cytokine signaling or tumor suppressorrelated genes and metastasis-inhibitory transcription factors. Down-regulated miRs promote epithelial-mesenchymal transition or mesenchymal-epithelial transition and diverse pro-metastatic signaling pathways. Some of the discussed miRs exert their function by simultaneously targeting epigenetic pathways as well as cell-cycle-related, antiapoptotic and signaling-promoting targets. Finally, we discuss potential therapeutic options for the treatment of prostate cancer-related metastases by substitution or inhibition of miRs. In 2017, 160,000 new cases of prostate cancer (PC) were diagnosed in the US and an equal number in the EU with 27,000 patients dying due to metastatic PC in the US and the EU (1). Localized disease can be potentially cured by therapies such as surgery and radiation, but in some patients, the disease progresses despite these therapies (2). Androgendeprivation therapy leads to long-lasting responses between 2 and 3 years, however the disease inevitably progresses to castration-resistant prostate cancer (CRPC) that is associated with metastatic disease and poor prognosis. Over the past 5 years, five drugs have been approved for treatment of CRPC (2). These are cabazitaxel, a taxane-based cytostatic; radium 223, an α-emitter; enzalutamide, a small-molecule androgen receptor (AR) antagonist; abiraterone, a blocker of de novo synthesis of androgens; and Sipuleucel, a dendritic cell-based immunotherapy (3). The recent genetic classification of PC has revealed seven subtypes and new molecular targets for molecular intervention such as vets erythroblastosis virus E26 homolog (ETS) family transcription factor-based fusion proteins as well as mutations in speckle-type POZ protein (SPOP), forkhead protein A1 (FOXA1) and isocitrate dehydrogenase 1 (IDH1) (4). The serine protease inhibitor Kazal-type 1 (SPINK), which is up-regulated in ETSrearrangement-negative tumors, is also being pursued as a new target for treatment of CRPC (5). Nucleic acid-based therapy is another approach for treatment of CRPC. Custirsen, a second-generation phosphorothioate antisense oligonucleotide targeting clusterin mRNA is presently undergoing phase III clinical studies in combination with chemotherapy in patients with CRPC (6, 7). Clusterin is upregulated in patients with CRPC and functions as an ATPindependent molecular chaperone with anti-a...

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Section: Therapeutic Aspectsmentioning

confidence: 99%

The Functional Role of Prostate Cancer Metastasis-related Micro-RNAs

Weidle

Epp

Birzele

et al. 2018

Cancer Genomics Proteomics

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“…One possibility is to perform the conjugation of chimeras to short cell penetration cationic peptides (CPPs) that are important for the efficiency in intracellular transport of a variety of macromolecules [42]. Another possibility is the conjugation of the chimeras with peptides from the transactivator of transcription (TAT)region; Diao et al demonstrated that the survivin siRNA was delivering specifically and efficiently and suppressed tumor growth in prostate cancer in vivo [43]. Inclusion of endosome-disrupting molecules, including PEI and poly (histidine), as well as fusogenic lipids and pH-sensitive lipids in aptamer-siRNA chimeras, have been useful for enhancing siRNA endosomal evasion [24,44,45].…”

Section: Aptamer In the Delivery Of Therapeutic Nanoparticles Containmentioning

confidence: 99%

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

Almeida

et al. 2019

Pharmaceutics

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Both aptamers and siRNA technologies have now reached maturity, and both have been validated with a product in the market. However, although pegaptanib reached the market some time ago, there has been a slow process for new aptamers to follow. Today, some 40 aptamers are in the market, but many in combination with siRNAs, in the form of specific delivery agents. This combination offers the potential to explore the high affinity and specificity of aptamers, the silencing power of siRNA, and, at times, the cytotoxicity of chemotherapy molecules in powerful combinations that promise to delivery new and potent therapies. In this review, we report new developments in the field, following up from our previous work, more specifically on the use of aptamers as delivery agents of siRNA in nanoparticle formulations, alone or in combination with chemotherapy, for the treatment of cancer.

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“…When low-molecular-weight protamine (LMWP) was combined with human fibroblast growth factor 2 (hFGF2) or human vascular endothelial growth factor, cell permeability was significantly increased, suggesting that it could be used as an effective percutaneous delivery system [15]. The anticancer effect in vivo was confirmed using a fusion complex composed of triplicated Tat, siRNA, and target-specific aptamers [16]. In addition, the efficiency of CRISPR was increased by delivering Cas9 complexed with guide RNA intracellularly using a Tat adaptor system [17].…”

Section: Introductionmentioning

confidence: 99%

Cell-Penetrating Peptides Enhance the Activity of Human Fibroblast Growth Factor 2 by Prolonging the Retention Time: A New Vision for Drug-Delivery Systems

Lee¹,

Kwon

et al. 2020

IJMS

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Cell-penetrating peptides (CPPs) are defined by their ability to deliver cargo into cells and have been studied and developed as a promising drug-delivery system (DDS). However, the issue of whether the CPPs that have already entered the cells can be re-released or reused has not been studied. The purpose of this research was to construct CPP-conjugated human fibroblast growth factor 2 (hFGF2) and investigate whether they can be re-released from the cell membrane for reuse. This study combined hFGF2 with Tat or Ara27, a newly developed CPP derived from the zinc knuckle (CCHC-type) family protein of Arabidopsis. Human dermal fibroblast (HDF) was treated with Tat-conjugated hFGF2 (tFGF2) and Ara27-conjugated hFGF2 (NR-FGF2) for both long and short durations, and the effects on cell growth were compared. Furthermore, tFGF2 and NR-FGF2 re-released from the cells were quantified and the effects were evaluated by culturing HDF in a conditioned medium. Interestingly, the proliferation of HDF increased only when NR-FGF2 was treated for 1 h in endocytosis-independent manner. After 1 h, NR-FGF2 was significantly re-released, reaching a maximum concentration at 5 h. Furthermore, increased proliferation of HDF cultured in the conditioned medium containing re-released NR-FGF2 was discovered. While previous studies have focused on the delivery of cargo and its associated applications, this study has revealed that combinations of superior CPPs and therapeutics can be expected to prolong both the retention time and the cell-penetrating capacity, even in the presence of external factors. Therefore, CPPs can be applied in the context of topical drugs and cosmetics as a new DDS approach.

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A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growthin vivo

Cited by 23 publications

References 43 publications

The Functional Role of Prostate Cancer Metastasis-related Micro-RNAs

The Functional Role of Prostate Cancer Metastasis-related Micro-RNAs

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

Cell-Penetrating Peptides Enhance the Activity of Human Fibroblast Growth Factor 2 by Prolonging the Retention Time: A New Vision for Drug-Delivery Systems

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