The clinical utility of 7-ethyl-10-hydroxycamptothecin (SN-38) is hampered by its low water solubility and reduced bioactivity at neutral or alkaline conditions. The rational design of an effective drug delivery system that can significantly enhance the therapeutic index of SN-38 and achieve complete tumor regression still remains a challenge. Herein, chitosan-based hybrid nanoparticles system co-loading with chemotherapeutic drug SN-38 and gold nanorods (AuNRs) was engineered for effective combinational photothermal-chemotherapy. To increase the solubility of SN-38, soluble polymeric prodrug poly (l-glutamic acid)-SN38 (l-PGA-SN38) was firstly synthesized and then complexed with chitosan to form stable nanomedicine via a mild and facile way without using any organic solvent or surfactant. Upon introducing AuNRs into chitosan-based nanomedicine by coordination interaction between the amine group of chitosan and AuNRs, the hybrid nanoparticles exhibited distinct synergistic therapeutic effect compared with single chemotherapy or photothermal treatment in vitro and in vivo. Almost complete tumor regression was achieved after 21-day treatment of the developed hybrid nanoparticles and showed no recurrence for at least 60 days.
Keywords: Chitosan; Combination therapy; Gold nanorod; Nanocomplexes; SN-38.
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