Functionalized turmeric nanovesicles for precision delivery of doxorubicin in colorectal carcinoma treatment

Abstract

Nanoscale vesicles have emerged as promising biocompatible vehicles for precision drug delivery, owing to their inherent therapeutic properties and versatile structural configurations. This study introduces an innovative biomanufacturing strategy utilizing curcumin-extracted nanovesicles (TNVs) conjugated with a cancer-selective peptide and encapsulated with doxorubicin to optimize therapeutic outcomes in colorectal malignancies. TNVs were purified through refined ultracentrifugation protocols, demonstrating uniform saucer-shaped morphology with an average size of 162.42 ± 3.67 nm and stable bilayer architecture dominated by triglyceride (30%) and ceramide (11.8%) constituents. Peptide-mediated surface functionalization substantially improved intracellular internalization efficiency in HCT-116 colon carcinoma models. The engineered TNV-P-D formulation exhibited potent tumoricidal activity (IC₅₀ = 54.8 μg/ mL), outperforming both unbound doxorubicin (IC₅₀ = 795.2 ng/mL) and nonfunctionalized TNV-DOX counterparts (IC₅₀ = 129.7 μg/mL). Cell cycle profiling revealed G1-phase blockade (91.3% G1-phase occupancy), corroborating the platform's proliferation-inhibiting capacity. In murine CT26. WT xenograft models, TNV-P-D administration achieved significant tumor regression (65% volume reduction, p< 0.001) while preserving hepatobiliary function and demonstrating negligible multiorgan toxicity. These results position peptide-augmented phytovesicles as a multifunctional therapeutic system capable of dual-action tumor targeting and systemic toxicity mitigation in colorectal oncology.

Keywords: biocompatible chemotherapy; colorectal carcinoma; drug encapsulation; tumor-homing peptide; turmeric nanocarriers.

FIGURE 1

A Transmission electron microscopy of TNVs,TVN-P,TNV-D,TVN-P-D.

FIGURE 2

NTA particle size distribution map of TNVs,TVN-P,TNV-D,TVN-P-D.

FIGURE 3

(A) Infrared pattern of TNVs; (B) Pie chart of lipid composition ratios.

FIGURE 4

Histogram of cytotoxicity at each concentration of (A) DOX; (B) Histogram of cytotoxicity of each concentration of TNVs; (C) Histogram of cytotoxicity of each concentration of TNV-P; (D) Histograms of cytotoxicity at each concentration of TNV-D (E); Histogram of cytotoxicity at each concentration of TNVs-P-D (Blank group VS Administration group *p < 0.05, **p < 0.01, ***p < 0.001) All values were expressed as mean ± SD (n = 3).

FIGURE 5

A Uptake of DOX cells; B TNV-D cell uptake map; C TNV-P-D cell uptake map; D TNVs cell uptake; E TNV-P cell uptake map.

FIGURE 6

(A) green fluorescence intensity; (B) red fluorescence intensity.

FIGURE 7

(A) Control cell cycle distribution; (B) DOX cell cycle distribution; (C) TNVs cell cycle distribution; (D) TNV-P cell cycle distribution; (E) TNV-D cell cycle distribution; (F) Cell cycle distribution of TNV-P-D.

FIGURE 8

(A) Tumor size between groups after the end of treatment; (B) Changes in body weight of mice during administration; (C) Change in tumor volume in each group; (D) Change in tumor weight in each group (Blank group VS Administration group *p < 0.05,**p < 0.01,***p < 0.001) All values were expressed as mean ± SD (n = 3).

FIGURE 9

In vivo imaging of small animals was used to detect the drug distribution of tumor-bearing mice after tail vein injection for 24 h.

FIGURE 10

Drug was distributed within the organ within 8 hours of administration.

FIGURE 12

HE staining of major organs.

FIGURE 11

(A) HE staining was used to detect the structural changes of tumor tissues after treatment with tumor-bearing mice; (B) Biochemical experiments were performed to detect the changes in liver function after treatment of tumor-bearing mice (AST) and (ALT) (Blank group VS Administration group *p < 0.05,**p < 0.01,***p < 0.001) All values were expressed as mean ± SD (n = 3).