Aptamer-conjugated and doxorubicin-loaded unimolecular micelles for targeted therapy of prostate cancer

Abstract

In the absence of effective therapy for prostate cancer, there is an immense need for developing improved therapeutic options for the management of this disease. This study has demonstrated that aptamer-conjugated unimolecular micelles can improve the in vivo tumor biodistribution of systemically administered anti-cancer drugs in prostate cancer expressing prostate-specific membrane antigen (PSMA). The aptamer-conjugated unimolecular micelles were formed by individual hyperbranched polymer molecules consisting of a hyperbranched H40 polymer core and approximately 25 amphiphilic polylactide–poly(ethlyene glycol) (PLA–PEG) block copolymer arms (H40-PLA-PEG-Apt). The unimolecular micelles with an average hydrodynamic diameter of 69 nm exhibited a pH-sensitive and controlled drug release behavior. The targeted unimolecular micelles (i.e., DOX-loaded H40-PLA-PEG-Apt) exhibited a much higher cellular uptake in PSMA positive CWR22Rν1 prostate carcinoma cells than non-targeted unimolecular micelles (i.e., DOX-loaded H40-PLA-PEG), thereby leading to a significantly higher cytotoxicity. The DOX-loaded unimolecular micelles up-regulated the cleavage of PARP and Caspase 3 proteins and increased the protein expression of Bax along with a concomitant decrease in Bcl2. These micelles also increased the protein expression of cell cycle regulation marker P21 and P27. In CWR22Rν1 tumor-bearing mice, DOX-loaded H40-PLA-PEG-Apt micelles (i.e., targeted) also exhibited a much higher level of DOX accumulation in the tumor tissue than DOX-loaded H40-PLA-PEG micelles (i.e., non-targeted). These findings suggest that aptamer-conjugated unimolecular micelles may potentially be an effective drug nanocarrier to effectively treat prostate cancer.

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

“…In addition, because the aptamer is a gene fragment in itself, it can be intercalated with anthracyclines or can be connected to other gene fragments, which can lay the foundation for future construction of targeted NBs carrying drugs (or genes) in targeted therapy under ultrasound irradiation. [41][42][43][44] …”

The effect of dual-functional hyaluronic acid-vitamin E succinate micelles on targeting delivery of doxorubicin

“…5,6 Therefore, active tumor-targeted PMs, which could be internalized by specific receptor-mediated endocytosis in tumor cells, and achieve a higher chemotherapy efficacy and are beneficial in reducing the side effects in normal tissues, have been extensively focused toward cancer treatment. 7,8 To achieve active targeting, various specific targeting ligands, such as folic acid, 9,10 peptide, [11][12][13] hyaluronic acid, [14][15][16] and other ligands, 17 have been grafted onto the surface of PMs, and then the PMs specifically interact with the receptor expressed on target cancer cells.…”

Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy

“…CH., chitosan; miR-inh, miRNA inhibitor. has been conjugated to doxorubicin micelles, which led to an increased uptake by PSMA-positive CWR22R-nu1 prostate cancer cells and resulted in higher cytotoxicity than that achieved using nontargeting micelles (25). More recently, a similar strategy was used in constructing 225 Ac-loaded liposomes to target and selectively kill PSMA-expressing cells such as LNCaP, Mat-Lu, and HUVEC using radiation (26).…”