GRPr-mediated photothermal and thermodynamic dual-therapy for prostate cancer with synergistic anti-apoptosis mechanism

Xu, Hang; Sheng, Gang; Lu, Lu; Wang, Cuirong; Zhang, Yu; Feng, Lili; Meng, Lingsen; Min, Pengxiang; Zhang, Li; Wang, Yijun; Han, Feng

doi:10.1039/d0nr07196j

Cited by 21 publications

(15 citation statements)

References 39 publications

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“…C-Jun is a representative member of the immediate early genes responding and adapting to a variety of stimuli and also participating in the transcription process of the effector enzymes of the signal transmission system [ 41 ]. P-JNK acts as key proteins involved in the cells' stress responses [ 42 ]. NMDA is involved in calcium influx of nerve cells and induced excitotoxicity, thereby increasing the level of P-JNK protein [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Total Panax Notoginseng Saponins on Retinal Ganglion Cells of an Optic Nerve Crush Injury Rat Model

Huang

Chen

et al. 2021

BioMed Research International

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Irreversible loss of retinal ganglion cells (RGCs) is a common pathological feature of various optic nerve degenerative diseases such as glaucoma and ischemic optic neuropathy. Effective protection of RGCs is the key to successful treatment of these diseases. Total Panax notoginseng saponins (TPNS) are the main active component of Panax notoginseng, which has an inhibitory effect on the apoptosis pathway. This study is aimed at assessing the protective effect of TPNS on RGCs of the optic nerve crush (ONC) model of rats and exploring the underlying mechanisms. The intraperitoneal or intravitreal injection of TPNS was used based on the establishment of the rat ONC model. Fifteen days after the injury, the cell membrane fluorescent probe (Fluoro-Gold) was applied to retrograde RGCs through the superior colliculus and obtain the number of surviving RGCs. TUNEL assay was also used to detect the number and density of RGC apoptosis after the ONC model. The expression and distribution of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK in the retina were demonstrated by Western blot analysis. After the intervention of TPNS, the rate of cell survival increased in different retinal regions ( p < 0.05 ) and the number of apoptosis cells decreased. Regarding the expression of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK-related apoptotic proteins, TPNS can reduce the level of apoptosis and play a role in protecting RGCs ( p < 0.05 ). These findings indicate that topical administration of TPNS can inhibit cell apoptosis and promote RGC survival in the crushed optic nerve.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Total Panax Notoginseng Saponins on Retinal Ganglion Cells of an Optic Nerve Crush Injury Rat Model

Huang

Chen

et al. 2021

BioMed Research International

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“…This approach led to the successful targeting of GRPR-positive breast cancer and Ehrlich tumor cells [71][72][73]. [35] polymeric micelles glioma Coumarin-6 Camptothecin (CPT) [61] prostate cancer Monomethyl auristatin F (MMAF) [65] elastin-like micelles prostate cancer - [63] Docetaxel (DTX) [74] nanostructured lipid carriers lung cancer Doxorubicin (DOX) [17] solid lipid nanoparticles breast cancer Doxorubicin (DOX) [59] PLGA nanoparticles breast cancer Docetaxel (DTX) [14] prostate cancer Docetaxel (DTX) [75] gold nanoparticles cervical cancer RAF peptide analog (Ac-Cys-Ahx-RAF) [69] prostate cancer 99m Tc [24] 99m Tc, 177 Lu [31] - [76] Gallic acid (GA) [47] prostate cancer, colon cancer 68 Ga [25] gold nanorods breast cancer Photothermal therapy -use of NIR laser irradiation [39] prostate cancer Heat-labile cytotoxic free radical donor -AIPH [77] graphene oxide glioblastoma Magnetic targeting, doxorubicin (DOX), NIR laser irradiation…”

Section: Ligand Incorporationmentioning

confidence: 99%

Nanostrategies for Therapeutic and Diagnostic Targeting of Gastrin-Releasing Peptide Receptor

Rurarz¹,

Bukowczyk²,

Gibka³

et al. 2023

Preprint

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Advances in nanomedicine bring the attention of researchers to the molecular targets which can play a major role in the development of novel therapeutic and diagnostic modalities for cancer management. The choice of a proper molecular target can decide on the efficacy of the treatment and endorse the personalized medicine approach. Gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled membrane receptor, well known to be overexpressed in numerous malignancies including pancreatic, prostate, breast, lung, colon, cervical and gastrointestinal cancers. Therefore, many research groups express a deep interest in targeting GRPR with their nanoformulations. A broad spectrum of the GRPR ligands has been described in the literature, which allows tuning of the properties of the final formulation, particularly in the field of the ligand affinity to the receptor and internalization possibilities. Hereby the recent advances in the field of applications of various nanoplatforms which are able to reach the GRPR expressing cells are reviewed.

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“…These non-radiolabeled cytotoxic BnR ligands are almost entirely directed at tumor overexpression of GRPRs and are composed of both GRPR agonists and antagonists ( 13 , 14 ). Furthermore, the non-radiolabeled BnR tumoral cytotoxic analogs described have utilized a wide range of cytotoxic agents ( 10 , 11 , 90 ), including coupling to established chemotherapeutic agents (doxorubicin, paclitaxel/other taxol analogs, camptothecin, epigallocatechin) ( 23 , 24 , 79 , 167 , 168 , 278 – 280 ) ( Table 1 ); various marine toxins (hemiasterlin, dolastatin) ( 281 , 282 ); to various photosensitizing/photothermal agents for administration of cytotoxic photodynamic therapy ( 10 , 283 ); to various cell-penetrating cytotoxic agents ( 74 , 175 , 284 ); to the antimicrobial peptide magainin ( 285 ); to various siRNA constructs ( 10 , 176 , 286 , 287 ); to various mitochondrial disruptive agents ( 10 , 13 ); and to various cytotoxins such as diphtheria toxin ( 10 , 13 , 288 ). Recently, an effective cytotoxic agent in vitro and in vivo in rats with intracranial orthotropic C6-glioblastoma tumors ( 175 ) was described, which was made by conforming micelles containing the cell-penetrating agent Tat, which has been shown to enhance treatment of brain tumors in experimental studies ( 249 ), with a BnR agonist peptide.…”

Section: Possible Role Of Bnr Ectopic/overexpression By Cns/neural Tumors For Tumor Imaging and For Treatment By Receptor-mediated Therapmentioning

confidence: 99%

Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy

et al. 2021

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G-protein-coupled receptors (GPCRs) are increasingly being considered as possible therapeutic targets in cancers. Activation of GPCR on tumors can have prominent growth effects, and GPCRs are frequently over-/ectopically expressed on tumors and thus can be used for targeted therapy. CNS/neural tumors are receiving increasing attention using this approach. Gliomas are the most frequent primary malignant brain/CNS tumor with glioblastoma having a 10-year survival <1%; neuroblastomas are the most common extracranial solid tumor in children with long-term survival<40%, and medulloblastomas are less common, but one subgroup has a 5-year survival <60%. Thus, there is an increased need for more effective treatments of these tumors. The Bombesin-receptor family (BnRs) is one of the GPCRs that are most frequently over/ectopically expressed by common tumors and is receiving particular attention as a possible therapeutic target in several tumors, particularly in prostate, breast, and lung cancer. We review in this paper evidence suggesting why a similar approach in some CNS/neural tumors (gliomas, neuroblastomas, medulloblastomas) should also be considered.

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GRPr-mediated photothermal and thermodynamic dual-therapy for prostate cancer with synergistic anti-apoptosis mechanism

Abstract: Conventional prostate cancer treatment strategies, including chemotherapy and radiotherapy, cannot effectively eradicate prostate cancer, especially castration resistance prostate cancer. Herein, we developed a novel nano therapy platform that consists of...

Cited by 21 publications

References 39 publications

Protective Effect of Total Panax Notoginseng Saponins on Retinal Ganglion Cells of an Optic Nerve Crush Injury Rat Model

Protective Effect of Total Panax Notoginseng Saponins on Retinal Ganglion Cells of an Optic Nerve Crush Injury Rat Model

Nanostrategies for Therapeutic and Diagnostic Targeting of Gastrin-Releasing Peptide Receptor

Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy

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