Metal ion ornamented ultrafast light-sensitive nanogel for potential in vivo cancer therapy

Abstract

A smart, ultrafast, light-responsive nanogel is a potential carrier for on-demand and immediate delivery of therapeutic agents. Here, a novel branched pentaerythritol poly(caprolactone)-b-poly(acrylic acid)-based smart, light-responsive nanogel has been fabricated by using ferric ion (Fe³⁺) as a cross-linker. The mentioned block copolymer has been synthesized by combining both the ring opening and atom transfer radical polymerization techniques. Branched structure of the polymer offers a minute amount (1.5 mol %) of Fe³⁺ sufficient for nanogel formation. The nanogel looks like a spherically shaped human brain holding the water molecule as like cerebrospinal fluid in the brain. The particle size of the nanogel has been tailored (between 30 and 450 nm) by separately varying both the molar concentration of Fe³⁺ and polymer chain length. The highly negative zeta potential (−46 mV) of the nanogel promotes its impressive colloidal stability and prolongs the circulation time in vivo. Nanogels securely hold the DOX molecules (maximum drug loading capacity: 26.2%). Exposure of light onto the nanogel (in the presence of lactic acid) produces immediate initiation of de-cross-linking followed by the release of DOX molecules (85.2% at 120 min). The nanogel shows significantly high uptake and acute toxicity against a cancerous cell line (C6 glioma) in vitro. Administration of the DOX-loaded nanogel on the C6 glioma rat model (in vivo) offered tremendous inhibition (∼91%) of tumor growth without any toxic side effects (confirmed by histopathology).