Photoresponsive hyaluronate nanogel as an anticancer drug carrier

Abstract

In this study, we introduced photolabile 4-(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy)butyric acid (HMNB) to prepare photoresponsive nanogels. Hyaluronate (HA) grafted with 4-(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy) butyric acid (HA-g-HMNB) was self organized in aqueous solution. Interestingly, HA-g-HMNB nanogels exhibited caging and photo-uncaging properties for an encapsulated antitumor drug. Photoactivation allowed accelerated antitumor drug release from uncaged nanogels. We found a significant improvement in KB tumor-cell-killing efficacy when this system was associated with local light irradiation.

Chlorin e6‐embedded starch nanogels for improved photodynamic tumor ablation

“…Cell Counting Kit‐8 (CCK‐8) was obtained from Dojindo Molecular Technologies Inc. (Japan). Mono‐carboxylated methoxy poly (ethylene glycol) (mPEG‐COOH, M w = 2 kDa) or poly ( L ‐lactic acid) (PLLA, M w = 1 kDa)‐ b ‐poly (ethylene glycol) (PEG, M w = 2 kDa) was prepared as described in our previous reports …”

“…Potato starch (200 mg) was pre‐activated using succinic anhydride (10 mg), DMAP (10 mg), DCC (40 mg), and NHS (40 mg) in DMSO (20 mL) containing TEA (1 mL) and pyridine (1 mL) at 25°C for 1 day and reacted with excess cystamine (250 mg) at 25°C for 1 day, producing the aminated starch (Starch‐NH 2 , Figure A). After that, the solution was dialyzed (using a Spectra/Por® MWCO 8 kDa dialysis membrane tube) against fresh DMSO for 2 days to remove the non‐reacted chemicals . The dialyzed solution was lyophilized.…”

“…Starch‐NH 2 (200 mg) was reacted with Ce6 (70 mg, pre‐activated using DCC [15 mg] and NHS [15 mg] in DMSO [5 mL] at 25°C for 4 h) at 25°C for 1 day, producing Ce6‐conjugated starch (Starch [Ce6], Figure A). The resulting solution was dialyzed (using a Spectra/Por® MWCO 8‐kDa dialysis membrane tube) against fresh DMSO for 2 days Then, the residual hydroxyl group of Starch (Ce6) was reacted with the carboxyl terminal group of mPEG‐COOH in DMSO (25 mL) containing DCC (900 mg) and DMAP (500 mg), TEA (1 mL), and pyridine (1 mL) at 25°C for 1 day, producing PEG‐conjugated Starch (Ce6) (Starch [PEG/Ce6]). The resulting solution was transferred to a pre‐swollen dialysis membrane tube (Spectra/Por® MWCO 8 kDa) against fresh DMSO to remove any unconjugated chemicals for 2 days, and additionally against deionized water for 2 days, and then lyophilized .…”

“…The resulting solution was dialyzed (using a Spectra/Por® MWCO 8‐kDa dialysis membrane tube) against fresh DMSO for 2 days Then, the residual hydroxyl group of Starch (Ce6) was reacted with the carboxyl terminal group of mPEG‐COOH in DMSO (25 mL) containing DCC (900 mg) and DMAP (500 mg), TEA (1 mL), and pyridine (1 mL) at 25°C for 1 day, producing PEG‐conjugated Starch (Ce6) (Starch [PEG/Ce6]). The resulting solution was transferred to a pre‐swollen dialysis membrane tube (Spectra/Por® MWCO 8 kDa) against fresh DMSO to remove any unconjugated chemicals for 2 days, and additionally against deionized water for 2 days, and then lyophilized . In addition, the terminal hydroxyl group of the PLLA block in PLLA‐ b ‐PEG (175 mg) was reacted with Ce6 (100 mg) in DMSO (25 mL) containing DCC (100 mg) and DMAP (100 mg), TEA (1 mL), and pyridine (1 mL) at 25°C for 1 day, producing Ce6‐conjugated PLLA‐ b ‐PEG (PLLA [PEG/Ce6]).…”

“…In addition, the terminal hydroxyl group of the PLLA block in PLLA‐ b ‐PEG (175 mg) was reacted with Ce6 (100 mg) in DMSO (25 mL) containing DCC (100 mg) and DMAP (100 mg), TEA (1 mL), and pyridine (1 mL) at 25°C for 1 day, producing Ce6‐conjugated PLLA‐ b ‐PEG (PLLA [PEG/Ce6]). The resulting solution was dialyzed using a pre‐swollen dialysis membrane tube (Spectra/Por® MWCO 1 kDa) in fresh DMSO for 2 days and additionally against deionized water for 2 days, and then lyophilized . The obtained PLLA (PEG/Ce6) was utilized as a starch‐lacking control particle group.…”