pH-Sensitive Long-Circulating Nanoliposomes with CU1 for Effective Against Lung Cancer.

INTRODUCTION

To address the poor water solubility and low bioavailability of the curcumin derivative CU1, this study constructed a long-circulating pH-sensitive nanoliposome (CU1-LCpHL) as its delivery system.

METHODS

The physicochemical properties, stability, and anti-lung cancer efficacy of CU1-LCpHL were systematically evaluated, including in vitro cellular assays (cellular uptake, apoptosis, proliferation, and migration), in vivo pharmacokinetics and pharmacodynamics, mechanistic studies, and immunohistochemical analysis.

RESULTS

CU1-LCpHL presented a spherical morphology with uniform particle size. Its lyophilized powder remained stable for at least three months at 25°C and exhibited sustained-release characteristics. In vitro experiments demonstrated that, compared to free curcumin (CU), free CU1, and long-circulating stable nanoliposomes (CU1-LSLN), CU1-LCpHL promoted more efficient cellular uptake, induced apoptosis, and significantly inhibited the proliferation and migration of lung cancer cells. Pharmacokinetic studies revealed that the area under the curve (AUC0-t) of CU1-LCpHL was 9.52-fold and 9.47-fold higher than that of CU and CU1, respectively, while its mean residence time (MRT0-t) was 3.37-fold and 7.69-fold longer, respectively. In vivo pharmacodynamic results indicated that the tumor-inhibition rate of CU1-LCpHL was 2.42-, 2.17-, and 1.37-fold higher than those of CU, CU1, and CU1-LSLN, respectively, with no significant organ toxicity or hemolysis observed. Mechanistic studies showed that CU1-LCpHL significantly upregulated Caspase-3, Caspase-9, and Bax, while downregulating the p-AKT/AKT ratio and Bcl-2 levels. Immunohistochemical analysis further confirmed that CU1-LCpHL markedly reduced the positive expression of Ki67, CD34, and VEGFR2, outperforming all other treatment groups.

CONCLUSION

CU1-LCpHL significantly enhances the delivery efficiency and antitumor efficacy of CU1, representing a promising nano-drug delivery system for lung cancer therapy.