Abstract
In the present work, hydroxyethyl starch-new indocyanine green (HES-IR-820) conjugates were developed for enhanced cancer photodynamic therapy. HES-IR-820 conjugates were prepared by the condensation reaction between IR-820 and amino groups modified HES. HES-IR-820 conjugates with IR-820 loading content of 2.0% (HES-IR-8202.0) and 3.2% (HES-IR-8203.2) were prepared and characterized by 1H NMR, FT-IR, HPLC, and UV–Vis. HES-IR-8202.0 and HES-IR-8203.2 are monomolecular nanosized particles with hydrodynamic diameters of around 10 nm. HES-IR-8202.0 and HES-IR-8203.2 exhibit significantly enhanced stability in pH 7.4 PBS buffer and pH 7.4 PBS buffer containing 10% fetal bovine serum as compared to free IR-820. HES-IR-8202.0 and HES-IR-8203.2 show limited drug release in pH 7.4 and pH 5.0 PBS buffer. HES-IR-8202.0 and HES-IR-8203.2 exhibit enhanced singlet oxygen generation under 808 nm laser irradiation and reduced cellular uptake amount as compared to free IR-820. The cellular uptake pathway study reveals that the lipid raft-mediated endocytosis and macropinocytosis are involved in the cellular uptake of HES-IR-8202.0 and HES-IR-8203.2. Compared to free IR-820, HES-IR-8202.0 and HES-IR-8203.2 show reduced cytotoxicity, enhanced in vitro antitumor effect under 0.3 W/cm2 808 nm laser irradiation, and similar in vitro antitumor effect under 0.6 W/cm2 808 nm laser irradiation. HES-IR-820 conjugates show significant potential for cancer photodynamic therapy.
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