Brain tumors represent an aggressive form of
cancer, posing significant challenges in achieving complete remission. Development of advanced
therapies is crucial for improving clinical outcomes in
cancer patients. This study aimed to create a novel treatment approach using dual-targeted
transferrin (TF) and
AS1411 conjugated
micelles, designed to enhance therapeutic effectiveness of
docetaxel (DTX) and facilitate
gadolinium (Gd) based imaging in
brain cancer.
Micelles were prepared using a slightly modified
solvent-casting method, and the dual-targeting
ligands were attached to the
micelle's surface through a physical adsorption process. Average particle size of
micelles ranged from 117.49 ± 3.90-170.38 ± 3.39 nm, with a low polydispersity index. Zeta potential ranged from - 1.5 ± 0.02 to - 18.7 ± 0.04 mV. Encapsulation efficiency of DTX in
micelles varied from 92.64 ± 4.22-79.77 ± 4.13 %. Simultaneously, encapsulation of Gd in
micelles was found to be 48.27 ± 3.18-58.52 ± 3.17, respectively. In-vitro drug release studies showed a biphasic sustained release profile, with DTX and Gd release continuing up to 72 h with their t50 % at 4.95, 11.29, and 24.14 h for GDTP, GDTP-TF and GDTP-TF-AS1411
micelles, respectively. Cytotoxicity effect of GDTP-TF-AS1411
micelles has shown significant improvement (P < 0.001) and reduced IC50 value up to 0.19 ± 0.14 μg/ml compared to Taxotere® (2.73 ± 0.73 μg/ml).
Theranostic study revealed higher accumulation of GDTP-TF and GDTP-TF-AS1411
micelles free GD treated animal brains. The AUC of GDTP-TF-AS1411
micelles exhibited 23.79 ± 17.82 μg.h/ml higher than Taxotere® (14.14 ± 10.59 μg.h/ml). These findings direct enhanced effectiveness in
brain cancer therapy leading to improved
therapeutics in
brain cancer patients. The combined targeted
ligands and therapeutic agents strategy can direct advancement in
brain cancer therapy and offer improved therapy for patients.