Ac 500

The copolymers of PLA-PEG–COOH were synthesized by ring-opening polymerization using previously reported with some modifications (Fig. 1)^{55 (link)}. Glassware were salinized by rinsing with a 5% methyl trichlorosilane solution in toluene, followed by rinsing with acetone, and left overnight to dry at 130 °C. Carboxylated PEG (0.02 g) and lactide monomers (0.1 g) were added to a round bottom flask and dissolved in 7 ml dried toluene and stannous octoate as a catalyst was then added to the solution and the reaction was carried out 6 h at 120 °C under nitrogen. The organic solvent was evaporated under vacuum condition by rotary evaporator. Unreacted lactide monomers were hydrolyzed by adding cold water and PLA-PEG–COOH copolymers crystalized by adding acetonitrile and chilled methanol under stirrer in room temperature. The mixture was then centrifuged for 30 min at 10,000 rpm. The resulting PLA-PEG–COOH was characterized by ¹H-NMR (500 MHz spectrometer, Bruker Ac 500, Germany) and FTIR spectrophotometry (Nicolet 550 A, USA).Figure 1

Schematic illustration of synthesizing PLA-PEG–COOH and preparing aptamer conjugated nanoparticles.

All reactions were carried out in dried flasks under an atmosphere of dry nitrogen unless otherwise specified. The reactions monitored either on HPLC or TLC for completion. All reagents and solvents used were used as received without further purification unless otherwise stated. Chemical purity of the intermediates and final compound was determined on Agilent 1100 series instrument. LC-MS was performed on Agilent 1100 instrument with Zorbax column (4.6 × 150 mm) eluted with 0.1% trifluoroacetic acid water/0.1% trifluoroacetic acid acetonitrile at 1 mL/min flow rate. Column chromatography was performed on silica gel 60 (40-63 μm). Nuclear magnetic resonance (NMR) spectra were recorded on a Varian 300 instrument operating at 300 MHz (¹H) or Bruker AC 500 instrument operating at 500 MHz (¹H), 125 MHz (¹³C). Chemical shifts δ were reported in parts per million (ppm) from tetramethylsilane (TMS) as internal standards (0.00 ppm). Abbreviations for signal coupling are as follows: s = singlet, d = doublet, t = triplet, q = quartet, dd = double doublet, m = multiplet. High resolution mass spectrum (ES, positive) was determined on a Thermo LTQ FT Ultra Mass Spectrometer.
PDOX was synthesized according to the previously reported chemical process [16 (link)-18 (link)], with the following 7 major steps.

¹H NMR (500 MHz) spectra were recorded in CDCl₃ at 25 °C on a Bruker AC-500 (Bruker, Karlsruhe, Germany) spectrometer calibrated relative to the residual solvent resonance. The ¹H NMR spectra of sample I and sample II are presented in Figure A1 (see Appendix A).