A Dual‐Targeting Octaguanidine–Doxorubicin Conjugate Transporter for Inducing Caspase‐Mediated Apoptosis on Folate‐Expressing Cancer Cells

Abstract

An efficient synthetic framework was assembled (G8-FKE-FA-Dox), consisting of a lysosome-targeting octaguanidine molecular transporter with a cathepsin B (cath B)-specific peptide substrate, folic acid, and the potent chemotherapeutic drug doxorubicin (Dox). Because the folate receptor (FR) and cath B are overexpressed in malignant cells, this transporter conjugate successfully executed lysosome-mediated transport of Dox to FR-positive tumor cells, illustrating this framework as an excellent targeted drug delivery system (TDDS). G8-FKE-FA-Dox was shown to exhibit selective toxicity toward FR-overexpressing cancer cells, with an IC50 value superior to that of the USFDA-approved Lipodox(TM) and proportional to that of free Dox via selective induction of apoptosis by the activation of caspases 8, 9, and 3. This TDDS was observed to be nontoxic to red blood cells and lymphocytes at neutral pH. Furthermore the tumor-targeting dissemination pattern of this system was revealed by monitoring the in vivo biodistribution of the carrier (G8-FKE-FA-FL) in normal and FR-overexpressing tumor-bearing mice.

Emergence of Gold‐Mesoporous Silica Hybrid Nanotheranostics: Dox‐Encoded, Folate Targeted Chemotherapy with Modulation of SERS Fingerprinting for Apoptosis Toward Tumor Eradication

“…This superior therapeutic effect could be due to the optimal drug loading and targeting efficiency of the TNEDS for more intensive localized applications without causing any nonspecific toxicity, especially in the case of easily accessible solid malignancies and potentiates the future preclinical investigations. The efficiency of tumor targeting by Au@SiO 2 ‐FL‐CS‐FA was notable, particularly considering that the mice used in this study were fed with a regular diet rather than a folate‐free diet, which is usually necessary to increase the detection sensitivity of the FR‐targeted delivery systems …”

“…The cytotoxicity was further confirmed with BrdU assay kit (colorimetric – 11647229001, Roche Diagnostics, IN, USA), and the experiments were carried out with the instructions given in the kit and the measurements were made at 450/690 nm. Evaluation of the effect of folic acid on the growth inhibitory capacity of the constructs was also carried out by MTT assay after the addition of 2 × 10 −3 m folic acid to the medium for 2 h as reported …”

Biogenic Cluster-Encased Gold Nanorods as a Targeted Three-in-One Theranostic Nanoenvelope for SERS-Guided Photochemotherapy against Metastatic Melanoma

“…Since any externally administrated agents face an initial encounter with blood components, it is necessary to evaluate the toxicity of the carriers toward red blood cells (RBCs). , In order to confirm the role of BSA-AuNC in increasing the biocompatibility, we conducted hemolysis assay using isolated peripheral RBCs. As evident from Figure S11, the CTAB-coated AuNR exhibited concentration-dependent and pH-independent lysis behavior.…”

Exploration of Biogenic Nano-chemobiotics Fabricated by Silver Nanoparticle and Galactoxyloglucan with an Efficient Biodistribution in Solid Tumor Investigated by SERS Fingerprinting

“…Acridine orange-ethidium bromide dual staining was performed as described earlier , and the cells were observed under a FITC filter (Olympus 1X51, Singapore). Observation of nuclei for any apoptosis-related changes was done with Hoechst 33342 staining using a 4’,6-diamidino-2-phenylindole filter (Olympus 1X51, Singapore) as described before . TUNEL assay (DeadEnd fluorometric TUNEL system, Promega, USA) was used to detect the incorporation of the fluorescein-12-dUTP in the fragmented DNA of apoptotic cells, using the terminal-deoxynucleotidyl-transferase recombinant (rTdT) enzyme as per the manufacturer’s instructions using propidium iodide as counterstain.…”