Solanesol Modified Pluronic F127 Triblock Copolymeric Micelles for Anticancer Drug Delivery

Pluronic F127 is widely used in micelle formulations, yet its application is limited by its poor stability and low drug loading capacity. Structural modification of F127 is therefore necessary to overcome these drawbacks. Carrier materials with intrinsic pharmacological activity can reduce metabolism-related toxicity and exert synergistic effects with loaded drugs, offering broad application prospects. Solanesol (SOL), a long-chain unsaturated polyisoprenoid, exhibits antitumor activity and favorable lipophilicity. In this study, a solanesol derivative, monosolanesyl succinate (MSS), was synthesized and conjugated via an amide bond to Pluronic F127 as a hydrophobic segment, forming a pH-sensitive therapeutic nanocarrier. The critical micelle concentration (CMC) of F127-MSS was 10-fold lower than that of F127, indicating a significantly improved stability. The resulting doxorubicin-loaded F127-MSS micelles (F127-MSS-DOX) had an average particle size of approximately 130 nm and a drug loading capacity of ∼ 6.2%, which was about 4 times higher than those of F127-DOX micelles. The F127-MSS-DOX micelles exhibited pH-responsive drug release, promoting drug accumulation at tumor sites while reducing the toxicity in normal tissues. They also demonstrated excellent dilution, plasma, and storage stability. Blank F127-MSS micelles showed inherent inhibitory effects on HepG-2 and MCF-7 cells, attributed to the pharmacological activity of MSS. Furthermore, F127-MSS-DOX micelles displayed potent antitumor activity, comparable to that of free DOX at high concentrations. In vivo studies confirmed that blank F127-MSS micelles moderately suppressed tumor growth, while F127-MSS-DOX micelles significantly inhibited tumor progression and markedly reduced the systemic toxicity of free DOX, owing to their high drug loading, superior stability, pH sensitivity, and synergistic antitumor effect. These findings highlight the great potential of F127-MSS-DOX micelles for tumor treatment.