Chondroitin Sulfate-Derived Paclitaxel Nanocrystal via π–π Stacking with Enhanced Stability and Tumor Targetability

• DOI: 10.1021/acsami.2c15881
• Publication Date: 2022-11-09T17:58:17Z
• Authors: Dandan Huang; Jiajia Gui; Xue Chen; Ruilian Yu; Tao Gong; Zhirong Zhang; Yao Fu
• Keywords: Mice; Drug Carriers; Paclitaxel; Cell Line, Tumor; Chondroitin Sulfates; Animals; Nanoparticles; 02 engineering and technology; 0210 nano-technology; Antineoplastic Agents, Phytogenic; Micelles; Polyethylene Glycols

Nanocrystals with high drug loading have become a viable strategy for solubilizing drugs poor aqueous solubility. It remains challenging, however, to synthesize nanocrystals sufficient stability and targeting potential. Here, we report novel nanocrystal platform synthesized using paclitaxel (PTX) Fmoc-8-amino-3,6-dioxaoctanoic acid (Fmoc-AEEA)-conjugated chondroitin sulfate (CS) (CS-Fmoc) via π-π stacking afford stable formulation CD44 targetability (PTX NC@CS-Fmoc). The PTX NC@CS-Fmoc exhibited rodlike shapes an average hydrodynamic size of 173.6 ± 0.7 nm (PDI = 0.11 0.04) up 31.3 0.6%. Next, was subjected lyophilization in the absence cryoprotectants long-term storage, after redispersion, displayed 205.3 2.9 0.15 0.01). In murine Panc02 cells, showed higher internalization efficiency than that without CS modification NC@F127) (P < 0.05) or CS-Fmoc micelles 0.05). Moreover, appeared accumulate both lysosomes Golgi apparatus, while accumulated specifically apparatus. orthotopic tumor-bearing mice model, tumor-specific accumulation micelles, which also demonstrated comparable tumor growth inhibition as Nab-PTX. Overall, CS-Fmoc-derived represent neat targeted chemotherapy great potential translational studies.