Platinum(iv) prodrug conjugated Pd@Au nanoplates for chemotherapy and photothermal therapy

Abstract

Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core–shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(IV) prodrug c,c,t-[Pt(NH₃)₂Cl₂(O₂CCH₂CH₂CO₂H)₂] to obtain a nanocomposite (Pd@Au–PEG-Pt) for combined photothermal–chemotherapy. The prepared Pd@Au–PEG-Pt nanocomposite showed excellent stability in physiological solutions and efficient Pt(IV) prodrug loading. Once injected into biological tissue, the Pt(IV) prodrug was easily reduced by physiological reductants (e.g. ascorbic acid or glutathione) into its cytotoxic and hydrophilic Pt(II) form and released from the original nanocomposite, and the NIR laser irradiation could accelerate the release of Pt(II) species. More importantly, Pd@Au–PEG-Pt has high tumor accumulation (29%ID per g), which makes excellent therapeutic efficiency at relatively low power density possible. The in vivo results suggested that, compared with single therapy the combined thermo–chemotherapy treatment with Pd@Au–PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pd@Au–PEG-Pt without irradiation or photothermal treatment using Pd@Au–PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pd@Au nanoplates as drug delivery carriers for multimode cancer treatment.