FULL PAPER © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 2207 wileyonlinelibrary.com 1. Introduction Cisplatin is a widely used chemothera- peutic drug in the clinic with great anti- tumor effects against a broad spectrum of cancers including testicular, bladder, head and neck, ovarian, and breast tumors by disrupting DNA structure in cancer cell nuclei. [1] However, severe dose-limiting toxicity (e.g., nephrotoxicity, neurotoxicity) and easy induction of multidrug resistance have enforced us to find new strategies for safer and more effective utility of cis- platin. Motivated by the excellent passive tumor accumulation of nanoparticles via the enhanced permeability and retention (EPR) effect, various different cisplatin based nanodrug delivery systems (NDDSs) have been fabricated and exhibit improved therapeutic effects simultaneously with sig- nificantly reduced side effects in the past years. One of them, lipoplatin, prepared via encapsulating cisplatin with fusogenic lipids, has finished its phase III clinical trial, showing superior efficacy to non- small cell lung cancer adenocarcinomas over cisplatin when used in combination with paclitaxel. [2–4] Apart from directly loading cisplatin into NDDSs, cisplatin prodrug prepared by introducing two extra ligands on the axial positions of cispl- atin has also been demonstrated to be a promising alternative strategy to minimize the side effects of cisplatin. [5,6] Owing to the diverse tunability of axial ligands, various cisplatin prodrugs with different physiochemical properties (e.g., hydrophobic, hydrophilic) have been successfully synthesized and formulated into nanostructures via different interactions in the past several years. [7–11] Some of those cisplatin-prodrug containing nano- particles have shown greatly improved therapeutic efficacies with obviously reduced toxic effects to the treated animals over original cisplatin attributing to the enhanced tumor accumulation and tumor-specific activation of cisplatin prodrugs. [10,12–14] Liposomes, as an effective drug delivery system, have been intensively explored since the first description in 1965 and then found a lot of successes in applications as NDDSs. [15–17] With sur- face modification, usually by polyethylene glycol (PEG), liposomes Cisplatin-Prodrug-Constructed Liposomes as a Versatile Theranostic Nanoplatform for Bimodal Imaging Guided Combination Cancer Therapy Liangzhu Feng, Min Gao, Danlei Tao, Qian Chen, Hairong Wang, Ziliang Dong, Meiwan Chen,* and Zhuang Liu* Up to date, a large variety of liposomal nanodrugs have been explored for cancer nanomedicine, showing encouraging results in both preclinical animal experiments and clinical treatment of cancer patients. Herein, a phospholipid conjugated with a cisplatin prodrug is used as the major structure component of liposomes together with other commer- cial lipids via self-assembling. By doping with 1,1′-dioctadecyl-3,3,3′,3′- tetramethylindotricarbocyanine iodide (DiR), a lipophilic dye with strong near infrared (NIR) absorbance and fluorescence, the obtained DiR-Pt(IV)- liposome is found to be an effective probe for in vivo NIR fluorescence and photoacoustic bimodal imaging. Attributing to its intrinsically doped cis-Pt(IV) prodrug, efficient photothermal conversion ability, and excellent tumor homing ability, DiR-Pt(IV)-liposome confers greatly enhanced thera- peutic outcomes in the combined photothermal-chemotherapy. Moreover, Pt(IV)-liposome is also demonstrated to be an efficient carrier for both small hydrophilic molecules and proteins, which are encapsulated inside the water-cavity of liposomes, further demonstrating the versatile functions of this nanoplatform. This study develops a unique type of liposomal nano- medicine with a prodrug conjugated phospholipid as the major structure component. Such Pt(IV)-liposome is featured with advantages including precisely defined/easily tunable drug compositions, stealth-like pharmacoki- netics, efficient tumor passive uptake, and the capabilities to simultaneously load with various types of imaging or therapeutic agents. DOI: 10.1002/adfm.201504899 Dr. L. Z. Feng, Prof. M. W. Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau Macau 999078, China E-mail: mwchen@umac.mo Dr. L. Z. Feng, M. Gao, D. L. Tao, Q. Chen, Dr. H. R. Wang, Z. L. Dong, Prof. Z. Liu Institute of Functional Nano & Soft Materials (FUNSOM) & Collaborative Innovation Center of Suzhou Nano Science and Technology Soochow University Suzhou 215123, China E-mail: zliu@suda.edu.cn Adv. Funct. Mater. 2016, 26, 2207–2217 www.afm-journal.de www.MaterialsViews.com