A multifunctional liposomal nanoplatform co-delivering hydrophobic and hydrophilic doxorubicin for complete eradication of xenografted tumors

Abstract

In the war against cancer, tremendous efforts have been made by using a nanoparticle-based anticancer drug system. However, it is still a great challenge to achieve complete cure and eradication of cancer through chemotherapy. Here, we present a new multifunctional liposomal nanoplatform simultaneously loaded with hydrophilic doxorubicin hydrochloride in the aqueous core and hydrophobic debydrochlorination doxorubicin in the lipid bilayer. Compared with the traditional nanoparticle-based drug delivery system, this nanocarrier has three unique functions including a high payload of the same therapeutic agents with different water-solubilities, highly selective delivery of cargos to tumor cells and long-acting time with tumors. An excellent in vitro antitumor potency can be achieved with an IC₅₀ of 0.91 μg mL⁻¹ for this liposome, which is only half the IC₅₀ of free doxorubicin. More importantly, extremely good antitumor efficacy in vivo is achieved since the mean tumor volume of all xenografted tumors is respectively ∼20% and ∼10% of that of the commercial liposomal doxorubicin formulation and the single doxorubicin liposomes on day 17 after being intravenously injected with the liposome nanoformulation 4 times. Moreover, the tumors were completely cured and eradicated on day 60 with no recurrence and the survival rate still remained at 70% after 365 days. Therefore, this multifunctional binary-drug loaded liposome provides a great potential platform for winning the war against cancer.