Herein we present an innovative approach to produce biocompatible, degradable, and stealth polymeric nanoparticles based on poly(lipoic acid), stabilized by a PEG-ended surfactant. Taking advantage of the well-known thiol-induced polymerization of lipoic acid, a universal and nontoxic nanovector consisted of a solid cross-linked polymeric matrix of lipoic acid monomers was prepared and loaded with active species with a one-step protocol. The biological studies demonstrated a high stability in biological media, the virtual absence of "protein" corona in biological fluids, the absence of acute toxicity in vitro and in vivo, complete clearance from the organism, and a relevant preference for short-term accumulation in the heart. All these features make these nanoparticles candidates as a promising tool for nanomedicine.