Water-Soluble Single-Chain Polymeric Nanoparticles for Highly Selective Cancer Chemotherapy

Functionalized amphiphilic polymers consisting of hydrophilic poly(ethylene glycol) pendant groups and a hydrophobic poly(epichlorohydrin) backbone can spontaneously self-organize into single-chain polymeric nanoparticles (SCPNs) in water, without exhibiting concentration-dependent effects or requiring additional reactive additives or subsequent purification. These SCPNs can effectively encapsulate the anticancer drug doxorubicin and have a high drug-loading capacity, desirable particle size distribution, and excellent drug-entrapment stability in serum-containing media or buffer solutions at various pH values; these unique physical and biological properties will be crucial to the achievement of smart drug delivery nanocarriers based on functional micelles. Cytotoxicity assays confirmed that the drug-loaded SCPNs were not cytotoxic toward normal cells but were significantly cytotoxic toward tumor cells under normal physiological conditions. Our results suggest that the drug-loaded SCPNs exert selective, targeted cytotoxic effects in cancer cells, without affecting healthy cells. Importantly, cellular uptake and flow cytometric assays confirmed that the drug-loaded SCPNs effectively targeted and entered the tumor cells via endocytosis and subsequently effectively promoted apoptotic cell death. Thus, this SCPN system has the ability to improve the overall therapeutic efficacy and safety of cancer chemotherapy.