Folate-modified lipid–polymer hybrid nanoparticles for targeted paclitaxel delivery

Figures & data

Figure 1 (A) The formation of PTX-loaded polymeric nanoparticles from PCL-PEG-PCL. (B) TEM image of PTX-loaded PCEP NPs.

Notes: Left scale bar =500 nm, right scale bar =200 nm.

Abbreviations: TEM, transmission electron microscopy; PCL-PEG-PCL, poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone); PTX, paclitaxel; PCEP NPs, polymeric nanoparticles formed from PCL-PEG-PCL; PEG, poly(ethylene glycol); PCL, poly(ε-caprolactone).

Figure 2 Characterization of PTX-loaded folate targeted nanoparticles of mixed lipid-shell and polymer core (FLPNPs).

Notes: (A) Schematic illustration of the formulation of PTX-loaded FLPNPs. (B) TEM image of PTX-loaded FLPNPs (left scale bar =200 nm, right scale bar =100 nm). (C) Confocal laser scanning fluorescence image of rhodamine-PE labeled PTX-loaded FLPNPs (scale bar =2 μm): (a) Rhodamine channel, (b) Transmitted light, (c) Merged.

Abbreviations: FLPNPs, folate modified lipid-shell and polymer-core nanoparticles; PCL-PEG-PCL, poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone); DSPE-PEG2000, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000]; PTX, paclitaxel; TEM, transmission electron microscopy.

Table 1 Physicochemical characterization of PTX-loaded PCEP NPs, LPNPs, and FLPNPs

Samples	Particle size (nm)	Polydispersity	Zeta potential (mV)	Drug loading content (%)	Encapsulation efficiency (%)
PCEP NPs	235.2±12.6	0.233±0.028	−12.5±0.6	26.52±0.86	90.33±1.25
LPNPs	271.5±7.2	0.146±0.017	−14.2±0.8	27.71±0.97	92.24±1.54
FLPNPs	279.9±8.7	0.173±0.021	−17.5±1.1	27.36±0.91	91.16±1.12

Notes: Data represent mean ± SD, n=3.

Abbreviations: PTX, paclitaxel; PCEP NPs, polymeric nanoparticles formed from PCL-PEG-PCL; LPNPs, lipid–polymer hybrid nanoparticles; FLPNPs, folate modified lipid-shell and polymer-core nanoparticles; PCL-PEG-PCL, poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone).

Figure 3 In vitro PTX release profiles from LPNPs and FLPNPs in 1.0 M sodium salicylate solutions (n=3).

Abbreviations: PTX, paclitaxel; LPNPs, lipid–polymer hybrid nanoparticles; FLPNPs, folate modified lipid-shell and polymer-core nanoparticles.

Figure 4 CLSM images of FR-positive EMT6 cells and FR-negative L929 cells after incubation with Nile Red-loaded LPNPs and FLPNPs for 2 h.

Notes: Row 1 and 2: EMT6 cells were used. Row 3 and 4: L929 cells were used. In row 1 and 3, LPNPs were used while in row 2 and 4, FLPNPs were used.

Abbreviations: FITC, fluorescein isothiocyanate; CLSM, confocal laser scanning microscopy; FR, folate receptor; LPNPs, lipid–polymer hybrid nanoparticles; FLPNPs, folate modified lipid-shell and polymer-core nanoparticles; h, hours.

Figure 5 The in vitro cellular uptake efficiency of EMT6 cells after incubation with Nile Red-loaded LPNPs and FLPNPs for 0.5, 2, and 24 h (n=6). *P<0.05.

Abbreviations: PTX, paclitaxel; LPNPs, lipid–polymer hybrid nanoparticles; FLPNPs, folate modified lipid-shell and polymer-core nanoparticles; h, hours.

Figure 6 The in vitro cell viability of EMT6 cells at various concentrations of the drug under 24, 48, and 72 h treatment with Taxol, PTX-loaded LPNPs, and PTX-loaded FLPNPs (n=6). *P<0.05.

Abbreviations: PTX, paclitaxel; LPNPs, lipid–polymer hybrid nanoparticles; FLPNPs, folate modified lipid-shell and polymer-core nanoparticles; h, hours.

Figure 7 In vivo antitumor efficacy (A) and body weight changes (B) after intratumoral injection of PTX-loaded LPNPs, PTX-loaded FLPNPs, Taxol injection, and saline on EMT6 tumor-bearing BALB/c mice. Each point represents the mean of tumor size ± SEM (n=10).

Abbreviations: PTX, paclitaxel; LPNPs, lipid–polymer hybrid nanoparticles; FLPNPs, folate modified lipid-shell and polymer-core nanoparticles; SEM, standard error of the mean.