PEGylated Oxidized Alginate-DOX Prodrug Conjugate Nanoparticles Cross-Linked with Fluorescent Carbon Dots for Tumor Theranostics

Abstract

Theranostic nanomedicine has recently emerged as an appealing approach for tumor chemotherapy. Here, for the first time, fluorescent carbon dots (Cdots) were used as cross-linker for tumor theranostic nanoparticles. Novel theranostic nanoparticles of approximately 27 nm with a doxorubicin (DOX) content of 0.2532 mg/mg (mPEG-OAL-DOX/Cdots) were designed by conjugating DOX onto mPEG-OAL/Cdots nanoparticles that were prepared by cross-linking the PEGylated oxidized alginate (mPEG-OAL) with Cdots. Due to the acid-labile Schiff base conjugating linkage, the theranostic prodrug nanoparticles showed low levels of DOX release in the simulated physiological media, which indicated premature drug leakage could be reduced during body circulation. Interestingly, the <i>in vitro</i> DOX release was triggered in the simulated tumor microenvironment without burst release. MTT assay and CLSM analysis showed that the mPEG-OAL/Cdots nanoparticles were noncytotoxic, but that the mPEG-OAL-DOX/Cdots theranostic nanoparticles exhibited high degrees of inhibition of cancer cells due to their nucleus-targeting DOX delivery. In addition, their cellular fluorescence characteristic demonstrated a potential application for imaging-guided drug delivery in tumor treatment.