Development and characterization of micelles for nucleolin-targeted co-delivery of docetaxel and upconversion nanoparticles for theranostic applications in brain cancer therapy

Despite the existence of several treatment modalities and advancements in cancer research, brain cancer is still incurable. Over-expression of nucleolin receptors on cancer cells has been explored in several studies. The study aimed to develop and characterize nucleolar-targeted theranostic pluronic F127-TPGS micelles for brain cancer therapy. The theranostic agents i.e., Docetaxel; DTX as a therapeutic agent, and the upconversion nanoparticles; UCNP as a diagnostic agent, were loaded into micelles by a slightly-modified solvent casting method. Micelles were further decorated with synthesized TPGS-AS1411 aptamer conjugate for targeting brain cancer cells. The prepared micelles were found between 90 and 165 nm, with a uniform homogeneous and narrow distribution in formulations. DTX and UCNP encapsulation efficiencies of micelles were found 74-88% and 38-40%, respectively. Micelles have depicted sustained release of DTX for as long as 72 h. Hemolytic assay confirmed that DUTPAS1411 aptamer micelles were found more biocompatible than Taxotere (R). The cytotoxicity results revealed that DTP, DUTP, and DUTP-AS1411 aptamer micelles achieved 4.20, 11.70, and 17.54-fold more effectiveness than Taxotere (R), after 24 h of therapy, respectively. In addition, DUTP-AS1411 aptamer micelles achieved higher tmax and Cmax of DTX up to 8-and 1.5-fold, respectively, compared to Taxotere (R) treated group. A similar trend was observed for the brain-distribution study as DUTP-AS1411 aptamer micelles were found more efficacious than Taxotere (R). The histopathology studies showed no toxicity and cellular damage even after the 14th and 28th day post i.v. administration of normal saline, DTP, DUTP, and DUTP-AS1411 aptamer micelles formulations whereas Taxotere (R) has reported to cause toxicity in brain tissues. The study revealed that DUTP-AS1411 aptamer micelles inherit promising and improved therapeutic efficacy, reduced toxicity, dosing frequency, and sustained drug release behavior which can be further exploited as a potential therapeutic approach for brain cancer.