Identification of protein kinase C beta as a therapeutic target for neuroendocrine prostate cancer and development of a nanoparticle-based therapeutic strategy

Qie, Yunkai; Cheng, Zhaoxia; Wu, Zhouliang; Qi, Feng; Li, Bozhao; Wu, Suying; Chu, Tianjiao; Lu, Zefang; Li, Suping; Nie, Guangjun

doi:10.1016/j.nantod.2022.101705

Cited by 3 publications

(3 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Qie et al fabricated a thrombin-binding aptamer and a functional polymer nanoparticle altered with SSTR2-targeted octreotide to deliver enzastaurin for neuroendocrine prostate cancer treatment in order to solve these problems. According to in vitro and in vivo results, the specially formulated nanomedicine effectively inhibited the growth of tumors and the frequency of coagulation disorders [ 174 ].…”

Section: Aptamers (Novel) Mediated Drug Delivery Systemsmentioning

confidence: 99%

Emerging Trends of Nanomedicines in the Management of Prostate Cancer: Perspectives and Potential Applications

Deshmukh,

Singh,

Harwansh

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

Prostate cancer is one of the most life-threatening disorders that occur in males. It has now become the third most common disease all over the world, and emerging cases and spiking mortality rates are becoming more challenging day by day. Several approaches have been used to treat prostate cancer, including surgery, radiation therapy, chemotherapy, etc. These are painful and invasive ways of treatment. Primarily, chemotherapy has been associated with numerous drawbacks restricting its further application. The majority of prostate cancers have the potential to become castration-resistant. Prostate cancer cells exhibit resistance to chemotherapy, resistance to radiation, ADT (androgen-deprivation therapy) resistance, and immune stiffness as a result of activating tumor-promoting signaling pathways and developing resistance to various treatment modalities. Nanomedicines such as liposomes, nanoparticles, branched dendrimers, carbon nanotubes, and quantum dots are promising disease management techniques in this context. Nanomedicines can target the drugs to the target site and enhance the drug’s action for a prolonged period. They may also increase the solubility and bioavailability of poorly soluble drugs. This review summarizes the current data on nanomedicines for the prevention and treatment of prostate cancer. Thus, nanomedicine is pioneering in disease management.

show abstract

Section: Aptamers (Novel) Mediated Drug Delivery Systemsmentioning

confidence: 99%

Emerging Trends of Nanomedicines in the Management of Prostate Cancer: Perspectives and Potential Applications

Deshmukh,

Singh,

Harwansh

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…For instance, the expression level of SSTR2 was found to be elevated following hormone depletion therapy [ 22 ], and high uptake of 68 Ga-DOTATATE was observed in biochemically relapsed prostate cancer [ 1 , 31 ]. Most recently, targeting of SSTR2 was reported as a practical strategy to develop a polymeric nanoparticle system for NEPC therapy [ 32 ]. Therefore, we chose SSTR2 as a model NEPC target for the design of our T-SMPDC, DOTA-PEG 3 -TZ(PEG 4 -Octr)-PEG 2 -Trz-PEG 3 -Val-Cit-pABOC-FTY720.…”

Section: Introductionmentioning

confidence: 99%

A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer

et al. 2023

View full text Add to dashboard Cite

After androgen deprivation therapy, a significant number of prostate cancer cases progress with a therapy-resistant neuroendocrine phenotype (NEPC). This represents a challenge for diagnosis and treatment. Based on our previously reported design of theranostic small-molecule prodrug conjugates (T-SMPDCs), herein we report a T-SMPDC tailored for targeted positron emission tomography (PET) imaging and chemotherapy of NEPC. The T-SMPDC is built upon a triazine core (TZ) to present three functionalities: (1) a chelating moiety (DOTA: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for PET imaging when labeled with 68Ga (t1/2 = 68 min) or other relevant radiometals; (2) an octreotide (Octr) that targets the somatostatin receptor 2 (SSTR2), which is overexpressed in the innervated tumor microenvironment (TME); and (3) fingolimod, FTY720—an antagonist of sphingosine kinase 1 that is an intracellular enzyme upregulated in NEPC. Polyethylene glycol (PEG) chains were incorporated via conventional conjugation methods or a click chemistry reaction forming a 1,4-disubstituted 1,2,3-triazole (Trz) linkage for the optimization of in vivo kinetics as necessary. The T-SMPDC, DOTA-PEG3-TZ(PEG4-Octr)-PEG2-Trz-PEG3-Val-Cit-pABOC-FTY720 (PEGn: PEG with n repeating ethyleneoxy units (n = 2, 3, or 4); Val: valine; Cit: citrulline; pABOC: p-amino-benzyloxycarbonyl), showed selective SSTR2 binding and mediated internalization of the molecule in SSTR2 high cells. Release of FTY720 was observed when the T-SMPDC was exposed to cathepsin B, and the released FTY720 exerted cytotoxicity in cells. In vivo PET imaging showed significantly higher accumulation (2.1 ± 0.3 %ID/g; p = 0.02) of [68Ga]Ga-DOTA-PEG3-TZ(PEG4-Octr)-PEG2-Trz-PEG3-Val-Cit-pABOC-FTY720 in SSTR2high prostate cancer xenografts than in the SSTR2low xenografts (1.5 ± 0.4 %ID/g) at 13 min post-injection (p.i.) with a rapid excretion through the kidneys. Taken together, these proof-of-concept results validate the design concept of the T-SMPDC, which may hold a great potential for targeted diagnosis and therapy of NEPC.

show abstract

“…Protein kinase inhibitors have gained significant interest as potential kinase-targeted drugs due to their ability to inhibit protein kinase activity. , Therefore, screening protein kinase inhibitors is of great importance. We selected H-89, a PKA inhibitor, to assess the potential of our proposed biosensor in exploring the mechanism of PKA inhibition.…”

mentioning

confidence: 99%

Graphene Oxide-Mediated Regulation of Volume Exclusion and Wettability in Biomimetic Phosphorylation-Responsive Ionic Gates

Shi,

Nie,

Sha

et al. 2023

Nano Lett.

View full text Add to dashboard Cite

Replicating phosphorylation-responsive ionic gates via artificial fluidic systems is essential for biomolecular detection and cellular communication research. However, current approaches to governing the gates primarily rely on volume exclusion or surface charge modulation. To overcome this limitation and enhance ion transport controllability, we introduce graphene oxide (GO) into nanochannel systems, simultaneously regulating the volume exclusion and wettability. Moreover, inspired by (cAMP)-dependent protein kinase A (PKA)-regulated L-type Ca2+ channels, we employ peptides for phosphorylation which preserves them as nanoadhesives to coat nanochannels with GO. The coating boosts steric hindrance and diminishes wettability, creating a substantial ion conduction barrier, which represents a significant advancement in achieving precise ion transport regulation in abiotic nanochannels. Leveraging the mechanism, we also fabricated a sensitive biosensor for PKA activity detection and inhibition exploration. The combined regulation of volume exclusion and wettability offers an appealing strategy for controlled nanofluidic manipulation with promising biomedical applications in diagnosis and drug discovery.

show abstract

Identification of protein kinase C beta as a therapeutic target for neuroendocrine prostate cancer and development of a nanoparticle-based therapeutic strategy

Cited by 3 publications

References 50 publications

Emerging Trends of Nanomedicines in the Management of Prostate Cancer: Perspectives and Potential Applications

Emerging Trends of Nanomedicines in the Management of Prostate Cancer: Perspectives and Potential Applications

A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer

Graphene Oxide-Mediated Regulation of Volume Exclusion and Wettability in Biomimetic Phosphorylation-Responsive Ionic Gates

Contact Info

Product

Resources

About