N n 0 dicyclohexylcarbodiimide

Anhydrous 1,4-dioxane, dichloromethane, sodium bicarbonate (NaHCO 3 ), sodium sulfate (Na 2 SO 4 ), and triphenylphosphine were purchased from Acros Organics (Geel, Belgium). Boc-6aminohexanoic acid was purchased from Bachem (Weil am Rhein, Germany). Diethyl ether was obtained from CSC Ja ¨cklechemie (Nuremberg, Germany). Eight-armed poly(ethylene glycol) with a molecular mass of 40 000 Da (8armPEG40k-OH) was purchased from JenKem Technology (Allen, TX, USA). Ceteareth-20 was obtained from Kolb Distribution Ltd (Hedingen, Switzerland). Acetyl chloride, 12-aminododecanoic acid, anhydrous dimethylformamide, anhydrous tetrahydrofuran, deuterated chloroform (CDCl 3 ), N,N 0 -dicyclohexylcarbodiimide (DCC), diisopropyl azodicarboxylate, N,N-diisopropylethylamine, di-tert-butyl dicarbonate, fluorescamine, 3-(2-furyl)propanoic acid, N-hydroxysuccinimide (NHS), N-methoxycarbonylmaleimide, piperidine, and pyrene were received from Sigma-Aldrich (Taufkirchen, Germany). All other chemicals were obtained from Merck KGaA (Darmstadt, Germany). Bevacizumab (Avastin s , 25 mg mL À1 , Roche Ltd, Basel, Switzerland) was kindly provided by the hospital pharmacy of the University of Regensburg (Germany). Purified water was freshly prepared using a Milli-Q water purification system (Millipore, Schwalbach, Germany).

The PLGA copolymer with a free carboxylic acid (LA/ GA = 50:50 M ratio Resomer RG 502H, weight average MW:12,000 g/mol) was obtained from Boehringer-Ingelheim (Ingelheim, Germany). Poly (ethylene glycol) (PEG)-bis-amine [NH2-PEG-NH2] (weight average MW: 3350 g/mol), N,N 0 -Dicyclo hexylcarbodiimide (DCC), sulfo-N-hydroxysuccinimide (NHS), Polyvinyl alcohol (PVA) (weight average MW: 9000-10,000 g/mol) and Didodecyldimethylammonium bromide (DMAB) were purchased from Sigma Aldrich (St. Louise, MO, USA). Nile red with 99% purity was obtained from ACROS Organic (Geel-Belgium). Enzymatic agents for protein digestiondithiothreitol (DTT) and trypsin (proteomics grade) were purchased from sigma Aldrich (St. Louise, MO, USA). Ethyl acetate and acetone with purity of 99.5% were purchased from Merck (Darmstadt, Germany). LC-MS grade acetonitrile and formic acid were obtained from Fisher Scientific (Ottawa, ON, Canada). High quality water (Millipore, USA) was used throughout the experiment. All other utilized materials and analytical grade chemicals were purchased from Sigma Aldrich (St. Louise, MO, USA) without further purification.