Anticancer Activity of Dendriplexes against Advanced Prostate Cancer from Protumoral Peptides and Cationic Carbosilane Dendrimers

Abstract

The interaction of neuropeptides, vasoactive intestinal peptide (VIP), or growth hormone-releasing hormone (GHRH), with a cationic carbosilane dendrimer forms dendriplexes with antitumoral behavior in advanced prostate cancer cells PC3. At the concentrations used for dendriplexes formation, the free peptides were protumoral and prometastatic in advanced prostate cancer, while dendrimer only showed low cytotoxicity, but did not avoid the metastatic behavior of PC3 cells. However, these nanoplexes favored also cell adhesion and avoided cell migration. Also, the dendriplexes were not toxic for no tumoral prostate cells (RPWE-1) or fibroblasts. The use of labeled GHRH peptide (rhodamine labeled) and a dendrimer (fluorescein labeled) allowed us to observe that both systems reach the intracellular milieu after dendriplex formation. The treatment of PC3 cells with the nanoplexes reduced expression of vascular endothelial growth factor (VEGF) and cyclic adenosine monophosphate (cAMP). Molecular modeling analysis highlights the important contribution of the carbosilane framework in the stabilization of the dendriplex, since dendrimer interacts with a peptide region where hydrophobic amino acids are presented.

Cationic Carbosilane Dendrimers Prevent Abnormal α-Synuclein Accumulation in Parkinson’s Disease Patient-Specific Dopamine Neurons

“…For the present studies, we focused on carbosilane dendrimers as they have been proven to be effective in a variety of biomedical applications in a topology-dependent manner ,− and non-toxic at concentrations below 5 μM when used as transfecting or anti-cancer agents. , One of the main properties of carbosilane dendrimers is their inherent hydrophobicity, provided by their characteristic skeleton, which allows interaction with biological membranes in an efficient manner and the presence of a permanent number of charges. For this reason, low generations of carbosilane dendrimers are effective for most applications, unlike the case of other dendritic skeletons.…”

pH-Sensitive Dendrimersomes of Hybrid Triazine-Carbosilane Dendritic Amphiphiles-Smart Vehicles for Drug Delivery

“…Dendritic molecules, dendrimers and dendrons, are versatile platforms to design supramolecular nanoconstructions for robust drug delivery [ 4 , 5 , 6 , 7 , 8 ]. In particular, carbosilane dendrimers are efficient tools for antibacterial [ 9 ] and antiviral therapy [ 10 ], nucleic acid delivery [ 11 ], cancer treatment [ 12 ], imaging [ 13 ], functional nanomaterials [ 14 , 15 ], and so on. It should be noted that dendritic architectures give room to design various types of supramolecular constructions based on the molecular topology of building blocks.…”

Silver (I) N-Heterocyclic Carbenes Carbosilane Dendritic Systems and Their Imidazolium-Terminated Analogues as Antibacterial Agents: Study of Their Mode of Action

“…Carbosilane dendrimers are one type of dendritic structures based on silicon-carbon bonds, providing thermal and chemical stability. These properties as well as the biocompatibility showed for these systems are really advantageous for medical application [ 25 , 26 ].…”