Hybrid curcumin–phospholipid complex-near-infrared dye oral drug delivery system to inhibit lung metastasis of breast cancer

Abstract

Background:

Oral route of administration is preferred for treating breast cancer, especially when continued disease management with good tolerability is required; however, orally administered chemotherapeutics combined with near-infrared (NIR) dyes are hindered by the low bioavailability, insufficient for the desired therapeutic efficacy. In this study, we developed a hybrid self-microemulsifying drug delivery system for co-loading curcumin–phospholipid complex and NIR dye IR780 (CUR/IR780@SMEDDS), to achieve combined phototherapeutic and chemotherapeutic effects against lung metastasis of breast cancer.

Methods:

CUR/IR780@SMEDDS were characterized. The efficacy against breast cancer metastasis was evaluated by photothermal and photodynamic assessment, cytotoxicity, invasion, and migration in metastatic 4T1 breast cancer cells in vitro, and in vivo oral bioavailability study in rats and pharmacodynamics studies in tumor-bearing nude mice.

Results:

CUR/IR780@SMEDDS improved oral bioavailability of curcumin and IR780 in rats compared with curcumin and IR780 suspensions. CUR/IR780@SMEDDS exhibited remarkable photothermal and photodynamic effects in vitro. In metastatic 4T1 breast cancer cells, CUR/IR780@SMEDDS combined with localized NIR laser irradiation induced significant cytotoxicity and inhibited invasion and migration of 4T1 cells, an outcome attributable to cumulative effects of IR780-induced hyperthermia and pharmacological effects of curcumin. In orthotopic 4T1 tumor-bearing nude mice, combination of oral administration of CUR/IR780@SMEDDS with local NIR laser irradiation inhibited tumor progression and suppressed lung metastasis.

Keywords:

• curcumin
• IR780
• oral drug delivery
• lung metastasis of breast cancer
• photo/chemotherapy

Acknowledgment

This work was supported by the National Natural Science Foundation of China [Grant No. 81773913 and 81303232].

Disclosure

The authors report no conflicts of interest in this work.

Supplemental materials

Figure S1 FTIR spectra of (A) Raw IR780, (B) PC, (C) physical mixture of IR780 and PC, and (D) IR780 PC formed by the phospholipid complex preparing process.

Figure S2 Confocal images of ROS generation by control under NIR irradiation (808 nm, 0.8 W/cm², 5 mins) and CUR@SMEDDS in 4T1 cells.

Figure S3 Confocal images of cellular uptake for CUR/IR780@SMEDDS in Caco-2 cells.

Figure S4 Confocal images of cellular uptake for CUR/IR780@SMEDDS in (A) 4T1 cells and (B) 4T1 cells under NIR irridiation (808 nm, 0.8 W/cm², 5 mins).

Figure S5 Photographs of the wound healing assay with 4T1 cells treated with control, IR780, CUR@SMEDDS, CUR/IR780@SMEDDS, control+NIR, IR780+NIR, and CUR/IR780@SMEDDS+NIR.

Figure S6 Histological examination of heart, liver, spleen, and kidney in tumor-bearing nude mice treated with control and CUR/IR780@SMEDDS+NIR.