Smart design and preclinical evaluation of folate-functionalized mesoporous nanoparticles for targeted paclitaxel delivery in cancer therapy

This work aims to assess mechanisms of synthesis of folate-conjugated mesoporous silica nanoparticles (MNPs) for targeted delivery of paclitaxel in cancer treatment. Paaclitaxel, while potent, suffers from poor solubility and severe side effects due to off-target toxicity. The important factors including particle size (140 ± 6 nm), zeta potential (-29.2 ± 1.5 mV), drug loading (11.3 ± 0.8%), and entrapment efficiency (89.5 ± 1.7%) were determined by response surface methodology (RSM) by employing polynomial equations derived from factorial design. In biological fluids, optimised MNPs had good stability, low degree of aggregation (≤5%) and low drug release (≤4%). <i>In vitro</i> cytotoxicity analysis established higher anti-cancer efficacy, the optimised formulation depicted 78.5% tumour cell mortality to contrast with the 58% with free paclitaxel. <i>In vivo</i>, the MNPs containing paclitaxel enhanced the tumour targeting effect with the 87% of tumours observed with the treatment, while Taxol^® was effective in only 65% of the cases, and free paclitaxel in 58%. These results highlight the promise of folate-decorated MNPs as an advanced nanocarrier for safer and more effective paclitaxel chemotherapy, with significantly reduced systemic toxicity compared to commercial Taxol^®. However, further studies assessing drug penetration in larger tumour volumes and addressing scalability for clinical are warranted.