O 7 azabenzotriazol 1 yl n n n n tetramethyluronium hexafluorophosphate hatu

Hydrogenated soybean phospholipids (HSPC), cholesterol (Chol), and distearoyl phosphoethanolamine-PEG₂₀₀₀-Acrylamide (DSPE-PEG₂₀₀₀-ACA) were purchased from Shanghai Ponsure Biotech, Inc. Four-arm poly(ethylene glycol) amine (Tetra-PEG-amine) was provided by Xiamen Sinopeg company. Dibenzocyclooctyne-acid (DBCO acid, ≥95%) was supplied by Xi’an ruixi Biological Technology Co., Ltd. O-(7-azabenzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (HATU, 99%) and glutathione (GSH, 99%) were purchased from J&K Scientific Ltd. N,N-diisopropylethylamine (≥99%, DIEA), N,N’-methylenebisAcrylamide (99%, MBAA), N,N,N’,N’-tetramethylethylenediamine (99%, TEMED), and anhydrous N,N-dimethylformamide (99.8%, DMF) were provided by Sigma. Ammonium persulfate (99.99%, APS) and 1,11-diazido-3,6,9-trioxaundecane (≥95%, N₃-PEG₃-N₃) were supplied by Aladdin. Acrylamide (99%, AM) was purchased from Adamas. Ethyl ether (≥99.7%, Et₂O) and chloroform (≥99%, CHCl₃) were provided by Sinopharm chemical reagent Co., Ltd. Ammonium sulfate (≥99%, (NH₄)₂SO₄) and PBS buffer (10×, pH 7.4) were supplied by Sangon Biotech company. The PBS buffer used in all experiments was diluted ten times. Deionized water was used to prepare all aqueous solutions. Other reagents and solvents were used as received.

Amantadine hydrochloride (Ada), and dithiodiglycolic acid (DTGA, ≥98%) 4′,6-diamidino-2-phenylindole (DAPI) were obtained from Sigma-Aldrich (St. Louis, MO, USA) and used without further purification. Doxorubicin hydrochloride (DOX·HCl) and sorafenib (SF) base was purchased from Dalian Meilun Biotech Co., Ltd. (Dalian, China). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl), 1-hydroxybenzotriazole hydrate (HOBt, 99%), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 99%), and N,N-diisopropylethylamine (DIPEA, 99%) was purchased from J&K Scientific (Beijing, China). Methoxypoly(ethylene glycol) succinimidyl succinate (PEG-NHS, M_n = 2000) was purchased from JenKem Technology Co., Ltd (Beijing, China). Other chemical reagents in the study were analytical grade and obtained from commercial sources. PEG-CD was synthesized according to the previous study (Peng et al., 2014 (link)) and the synthetic route was described in the supplementary data (Figure S1A). The ¹H NMR spectrum of PEG-CD was displayed in Figure S1B.