Polypeptide-Based Molecular Platform and Its Docetaxel/Sulfo-Cy5-Containing Conjugate for Targeted Delivery to Prostate Specific Membrane Antigen

Abstract

A strategy for stereoselective synthesis of molecular platform for targeted delivery of bimodal therapeutic or theranostic agents to the prostate-specific membrane antigen (PSMA) receptor was developed. The proposed platform contains a urea-based, PSMA-targeting Glu-Urea-Lys (EuK) fragment as a vector moiety and tripeptide linker with terminal amide and azide groups for subsequent addition of two different therapeutic and diagnostic agents. The optimal method for this molecular platform synthesis includes (a) solid-phase assembly of the polypeptide linker, (b) coupling of this linker with the vector fragment, (c) attachment of 3-aminopropylazide, and (d) amide and carboxylic groups deprotection. A bimodal theranostic conjugate of the proposed platform with a cytostatic drug (docetaxel) and a fluorescent label (Sulfo-Cy5) was synthesized to demonstrate its possible sequential conjugation with different functional molecules.

Magnetic Mesoporous Silica Nanorods Loaded with Ceria and Functionalized with Fluorophores for Multimodal Imaging

“…78 This fluorophore emitting in the red region is often used in biomedical research for cell and tissue labeling, as in this spectral range biological objects show low absorption and many detectors exhibit maximum sensitivity. 79 To attach the Cy5 dye to the MSR surface, N-hydroxysuccinimide (NHS) ester derivative of Cy5 ( Figure 7 a) was used and reacted with amine groups of APTES-functionalized silica surface, forming an amide bond ( Figure 7 b). 80 After the reaction of MSRs-NH 2 with Cy5, a blue product was observed.…”

“…MSRs were then functionalized with Cyanine5 (also described as Cy5, where Cy stands for cyanine, and the number 5 refers to the number of carbon atoms between the indolenine groups) . This fluorophore emitting in the red region is often used in biomedical research for cell and tissue labeling, as in this spectral range biological objects show low absorption and many detectors exhibit maximum sensitivity . To attach the Cy5 dye to the MSR surface, N-hydroxysuccinimide (NHS) ester derivative of Cy5 (Figure a) was used and reacted with amine groups of APTES-functionalized silica surface, forming an amide bond (Figure b) .…”

Synthesis and Preclinical Evaluation of Urea-Based Prostate-Specific Membrane Antigen-Targeted Conjugates Labeled with 177Lu

“…27,33 These ligand conjugates are already wellestablished for the delivery of fluorescent dyes as well as the therapeutic agents abiraterone, 34 docetaxel, 35 and monomethylauristatin E 36 and as a platform for bimodal conjugates. 37 DOTA chelating agent was chosen due to its excellent chelating properties toward both 68 Ga (PET/CT diagnostics) and 177 Lu (radionuclide therapy) radioisotopes and its numerous examples of successful biomedical applications. 38−43 Based on the binding specificity test, [ 177 Lu]Lu-13B, [ 177 Lu]Lu-13E, [ 177 Lu]Lu-13C, [ 177 Lu]Lu-13A, and [ 177 Lu]Lu-13F variants are specific for PSMA (Figure 1).…”

A Novel Docetaxel-Biotin Chemical Conjugate for Prostate Cancer Treatment

“…To improve its therapeutic outcomes and evade associated side effects, delivery strategies for DTX have been widely investigated [17,22]. As for treatment of prostate cancer, the prostate specific membrane antigen (PSMA), a transmembrane protein expressed by virtually all prostate cancers, has been suggested to be an important target for DTX treatment [23]. PSMA-targeted small-molecule DTX conjugates were found in in vitro and in vivo studies to have highly increased solubility with less toxic effects [24].…”