Platinum(iv) prodrug conjugated Pdu nanoplates for chemotherapy and photothermal therapy

Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pdu nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pdu nanoplates with a platinum(iv) prodrug c,c,t-[Pt(NH sub(3)) sub(2)Cl sub(2)(O sub(2)CCH sub(2)CH sub(2)CO sub(2)) sub(2)] to obtain a nanocomposite (Pdu-PEG-Pt) for combined photothermal-chemotherapy. The prepared Pdu-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, Pdu-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 Pdu-PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pdu-PEG-Pt without irradiation or photothermal treatment using Pdu-PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pdu nanoplates as drug delivery carriers for multimode cancer treatment.