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Ultrasmall PEGylated Cu Se nanoparticles with strong near-infrared absorption have been prepared by an ambient aqueous method. The resultant water-soluble and biocompatible nanoparticles are demonstrated to be a novel nanotheranostic agent for effective deep-tissue photoacoustic imaging, computed tomography imaging, single-photon emission computed tomography imaging, and photothermal therapy of cancer.

Cisplatin is a chemotherapeutic drug commonly used in clinics. However, acquired resistance confines its application in chemotherapeutics. To overcome the acquired resistance to cisplatin, it is reasoned, based on our previous findings of mediation of cellular responses by [Gd@C 82 (OH) 22 ] n nanoparticles, that [Gd@C 82 (OH) 22 ] n may reverse tumor resistance to cisplatin by reactivating the impaired endocytosis of cisplatin-resistant human prostate cancer (CP-r) cells. Here we report that exposure of the CP-r PC-3-luc cells to cisplatin in the presence of nontoxic [Gd@C 82 (OH) 22 ] n not only decreased the number of surviving CP-r cells but also inhibited growth of the CP-r tumors in athymic nude mice as measured by both optical and MRI. Labeling the CP-r PC-3 cells with transferrin, an endocytotic marker, demonstrated that pretreatment of the CPr PC-3-luc cells with [Gd@C 82 (OH) 22 ] n enhanced intracellular accumulation of cisplatin and formation of cisplatin-DNA adducts by restoring the defective endocytosis of the CP-r cancer cells. The results suggest that [Gd@C 82 (OH) 22 ] n nanoparticles overcome tumor resistance to cisplatin by increasing its intracellular accumulation through the mechanism of restoring defective endocytosis. The technology can be extended to other challenges related to multidrug resistance often found in cancer treatments.A s a major chemotherapeutic agent for tumor treatment, cisplatin remains a cornerstone of the present-day chemotherapy regimens against not only epithelial malignancies but also a number of metastatic and advanced malignancies (1, 2). However, because of high toxicity and easy development of drug resistance, successful treatment with cisplatin often is limited (3,4). Following the discovery of ATP-binding cassette (ABC) transporters and their roles in drug resistance in various types of tumors (5), much research has been done to explore the relationship between ABC transporter activity and specific chemotherapeutics, including cisplatin. Because no ABC transporter has been identified for "pumping" cisplatin out of cisplatin-resistant human prostate cancer (CP-r) cells (6-8), it would be difficult to sensitize CP-r cells by using any known strategy that targets resistant cancer cells by inhibiting multidrug resistance (MDR)-associated proteins on plasma membrane of the CP-r cells. Diffusion has been considered as a pathway for cisplatin to penetrate plasma membrane. Recently, studies have indicated that cisplatin entered cells by endocytosis and other mechanisms (9-12).To increase susceptibility of cancer cells to cisplatin, i.e., to reverse drug resistance, many efforts have been made through chemical modification, gene therapy, vector delivery, and other means (2, 9, 13). Combination of traditional chemotherapy with nanotechnology may provide a promising alternative for novel cancer treatments. The use of nanoparticles to sensitize tumor cells to cisplatin in vitro and in vivo has been described recently (14-16). In these studies, cisplatin-encap...