Invertible Micellar Polymer Nanoassemblies Target Bone Tumor Cells But Not Normal Osteoblast Cells

Figures & data

Figure 1.  Chemical structure and characteristics of the PEG600PTHF650 used in the study.

The chemical structure of the PEG₆₀₀PTHF₆₅₀ used in this study, and the molecular weight, polydispersity index, hydrophilic lipophilic balance and critical micelle concentration of the polymer sample. The chemical structure of the PEG₆₀₀PTHF₆₅₀ was confirmed by proton nuclear magnetic resonance (¹H NMR) spectroscopy and Fourier transform infrared spectroscopy [28]. To confirm the formation of micelles from PEG₆₀₀PTHF₆₅₀ in aqueous solution, CMC was measured via solubilization of a fluorescent probe, pyrene, to study the association behavior of amphiphilic polymers [28].

CMC: Critical micelle concentration; HLB: Hydrophilic lipophilic balance; m: Number of PEG fragments in amphiphilic invertible polymers macromolecules; Mw: Weight average molecular weight; n: Number of PTHF fragments in amphiphilic invertible polymers macromolecules; PDI: Polydispersity index.

Figure 2.  Physico-chemical properties of invertible micellar polymer nanoassemblies.

(A) The intensity ratio (I_336.5/I₃₃₃) of the excitation spectra of pyrene in PEG₆₀₀PTHF₆₅₀ solutions versus polymer concentration. (B) The sizes of blank and curcumin-loaded polymer micellar nanoassemblies as determined by dynamic light scattering.

IMA: Invertible micellar polymer nanoassembly.

Figure 3.  Osteosarcoma cell survival.

MG63 osteosarcoma cells were treated with IMAs and IMA-loaded curcumin at different concentrations for 48h (A). Effect of curcumin delivery on MG63 KHOS, LM7 and HOB cells at 72 h (B). IMAs: I, III, V, VII; curcumin-loaded IMAs: II, IV, VI, VIII.

HOB: Human osteoblast; IMA: Invertible micellar polymer nanoassembly.

Figure 4.  Effect of invertible micellar polymer nanoassemblies-delivered curcumin on cell cycle.

MG63 osteosarcoma cells were analyzed by fluorescence-activated cell sorting analysis after 24 h: (A) untreated, (B) IMAs and (C) curcumin-loaded IMAs.

IMA: Invertible micellar polymer nanoassembly.

Figure 5.  IMA-delivered curcumin uptake in bone cells; 20 μM IMAs (I) and IMA-loaded curcumin (II–IV) were exposed to MG63 osteosarcoma cells and normal human osteoblasts (HOB) for 30 min (I, II); 1 h (III) and 2 h (IV). No fluorescence was observed in HOB at 1 and 2 h.

HOB: Human osteoblast; IMA: Invertible micellar polymer nanoassembly.

Table 1.  Physical properties of blank and curcumin-loaded invertible micellar polymer nanoassemblies from PEG₆₀₀ PTHF₆₅₀ (1% w/v).

AIP	Drug loading (wt.%/wt. polymer)	Size (nm; blank)	Size (nm; loaded)	ζ-potential (mV; blank)	ζ-potential (mV; loaded)
PEG600PTHF650	10.8 ± 0.3	14.4 ± 0.3	19.9 ± 2.4	-28.2 ± 3.6	-19.4 ± 0.3

AIP: Amphiphilic invertible polymer; wt: Weight.

Hevus I , ModgilA, DanielsJ, KohutA, SunC, StafslienS, VoronovA. Invertible micellar polymer assemblies for delivery of poorly water-soluble drugsBiomacromolecules13(8), 2537–2545 (2012).

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