Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy

Figures & data

Figure 1 Synthesis scheme of block copolymer MPEG-b-PCL.

Abbreviations: CL, caprolactone; MPEG, methoxy poly(ethylene glycol); MPEG-b-PCL, methoxy poly(ethylene glycol)-b-poly(ε-caprolactone); Sn(Oct)₂, stannous octoate.

Figure 2 Typical ¹H-NMR spectra of block copolymer MPEG-b-PCL.

Notes: ¹H-NMR in CDCl₃ was used, with following results: peak a (δ=4.06 parts per million [ppm], CL repeating unit: –CO–CH₂–CH₂–CH₂–CH₂–CH₂–O–), b (δ=2.32 ppm, CL repeating unit: –CO–CH₂–CH₂–CH₂–CH₂–CH₂–O–), c (δ=1.62–1.67 ppm, CL repeating unit: –CO–CH₂–CH₂–CH₂–CH₂–CH₂–O–), and d (δ=1.38 ppm, CL repeating unit: –CO–CH₂–CH₂–CH₂–CH₂–CH₂–O–). Peak e is the solvent CDCl₃. The peak f at 3.65 ppm was assigned to the (–CH₂–CH₂) protons of the initiator MPEG.

Abbreviations: ¹H-NMR, proton nuclear magnetic resonance; MPEG, methoxy poly(ethylene glycol); MPEG-b-PCL, methoxy poly(ethylene glycol)-b-poly(ε-caprolactone); ppm, parts per million.

Figure 3 Schematic representation of the preparation techniques of PTX-loaded NPs and PTX-loaded NPs@PDA.

Abbreviations: NP, nanoparticle; PDA, polydopamine; PTX, paclitaxel; PTX-loaded NPs@PDA, PTX-loaded methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-b-PCL) NPs that had their surfaces modified with PDA; TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.

Table 1 Characterization of PTX-loaded NPs and PTX-loaded NPs@PDA

Sample	Size (nm)	PDI	ZP (mV)	LC (%)	EE (%)
PTX-loaded NPs	122.6±3.9	0.136	−21.4±4.7	17.5±1.28	97.3±5.0
PTX-loaded NPs@PDA	141.8±5.8	0.121	10.9±1.5	16.8±1.05	94.1±3.6

Note: Size indicates particle diameter; n=3.

Abbreviations: EE, encapsulation efficiency; LC, loading content; NP, nanoparticle; NPs@PDA, NPs that had their surfaces modified with PDA; PDA, polydopamine; PDI, polydispersity index; PTX, paclitaxel; ZP, zeta potential.

Figure 4 (A) DLS size distribution and (B) FESEM images of PTX-loaded MPEG-b-PCL NPs@PDA.

Abbreviations: DLS, dynamic light scattering; FESEM, field-emission scanning electron microscopy; NP, nanoparticle; PDA, polydopamine; PTX, paclitaxel; PTX-loaded MPEG-b-PCL NPs@PDA, PTX-loaded methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) NPs that had their surfaces modified with PDA.

Figure 5 The in vitro drug release profile of PTX-loaded NPs and PTX-loaded NPs@PDA.

Note: Data represent mean ± SEM (n=3).

Abbreviations: NP, nanoparticle; PDA, polydopamine; PTX, paclitaxel; PTX-loaded NPs@PDA, PTX-loaded NPs that had their surfaces modified with PDA; SEM, standard error of the mean.

Figure 6 CLSM images of A875 cells after 2-hour incubation with C6-loaded NPs and C6-loaded NPs@PDA.

Notes: The NPs and NPs@PDA were green (EGFP channel) and the cells were blue (stained by DAPI).

Abbreviations: C6, coumarin-6; CLSM, confocal laser scanning microscopy; DAPI, 4′,6-diamidino-2-phenylindole dihydrochloride; EGFP, enhanced green fluorescent protein; NP, nanoparticle; NPs@PDA, NPs that had their surfaces modified with PDA; PDA, polydopamine.

Figure 7 The cellular uptake efficiency of C6-loaded NPs and C6-loaded NPs@PDA at different NP concentrations.

Note: Data represent mean ± SEM (n=3; *P<0.05).

Abbreviations: C6, coumarin-6; NP, nanoparticle; NPs@PDA, NPs that had their surfaces modified with PDA; PDA, polydopamine; SEM, standard error of the mean.

Figure 8 Viability of A875 cells after incubation with PTX-loaded NPs and PTX-loaded NPs@PDA in comparison with viability after treatment with Taxol^® at the same PTX dose and drug-free NPs@PDA with the same amount of nanoparticles.

Notes: Incubation for (A) 12 hours; (B) 24 hours; and (C) 48 hours. Data represent mean ± SEM (n=3; *P<0.05, **P<0.01, ***P<0.001).

Abbreviations: NP, nanoparticle; NPs@PDA, NPs that had their surfaces modified with PDA; PDA, polydopamine; PTX, paclitaxel; SEM, standard error of the mean.

Figure 9 Tumor growth curve and weights of nude mice bearing A875 cell xenografts.

Notes: (A) Tumor growth curve of nude mice bearing A875 cell xenografts after injection with PTX-loaded NPs, PTX-loaded NPs@PDA, Taxol^®, and saline; (B) weights of the nude mice bearing A875 cell xenografts after injection with PTX-loaded NPs, PTX-loaded NPs@PDA, Taxol^®, and saline. Data represent mean ± SEM (n=5; *P<0.05, **P<0.01).

Abbreviations: NP, nanoparticle; NPs@PDA, NPs that had their surfaces modified with PDA; PDA, polydopamine; PTX, paclitaxel; SEM, standard error of the mean.