Multifunctional Cu1.94S-Bi2S3@polymer nanocomposites for computed tomography imaging guided photothermal ablation

SCIENCE CHINA Materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ARTICLES mater.scichina.com link.springer.com . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Published online 24 July 2017 | doi: 10.1007/s40843-017-9068-6 Multifunctional Cu1.94S-Bi2S3@polymer nanocomposites for computed tomography imaging guided photothermal ablation Xiaoquan Lu, Yuanbao Li, Xilin Bai, Gaofei Hu and Leyu Wang* ABSTRACT The doping of radiocontrast agent such as bismuth (Bi) in copper chalcogenide nanocrystals for computed tomography (CT) imaging guided photothermal therapy (PTT) has drawn increasing attention. However, the doping of Bi often suffers from the weak CT signal due to the low Bi doping concentration and deteriorates the PTT efficacy of copper chalcogenides. Here we report a multifunctional nanoprobe by encapsulating both Cu1.94S and Bi2S3 nanocrystals into a biocompatible poly(amino acid) matrix with size of ~85 nm for CT imaging guided PTT. The amount of nanocrystals and the ratio of Cu1.94S-to-Bi2S3 in the multifunctional nanocomposites (NCs) are tunable toward both high photothermal conversion efficiency (~31%) and excellent CT imaging capability (27.8 HU g L−1). These NCs demonstrate excellent effects for photothermal ablation of tumors after intratumoral injection on 4T1 tumor-bearing mice. Our study may provide a facile strategy for the fabrication of multifunctional theranostics towards simultaneous strong CT signal and excellent PTT. Keywords: multifunctional nanoprobe, CT imaging, photothermal therapy, Bi2S3, Cu1.94S INTRODUCTION Nanomaterials have attracted tremendous interest over the past decades and been widely used in biomedical fields including fluorescence imaging, positron emission tomography (PET), magnetic resonance imaging (MRI), hyperthermia treatment, and so on [1–9]. Nanomaterialsbased X-ray computed tomography (CT) has also drawn wide attention and been identified as a promising noninvasive diagnostic tool for clinical diagnosis due to its high resolution and the excellent penetration of X-ray [10,11]. Compared to the commonly used small molecule CT contrast agents such as iodinated molecules [12] that often suffer from short imaging time and potential renal toxicity by their rapid kidney’s clearance [13–15], the nanocrystal contrast agents such as Bi2S3, TaOx and Au nanoparticles (NPs) show several advantages including low toxicity, long imaging time, and high absorption coefficient [16–18]. In particular, bismuth-based NPs such as Bi2Se3 nanoplates and Bi2S3 nanorods have drawn significant attention [19,20], because bismuth element possesses high X-ray attenuation coefficient resulted from its high density (ρ) and atomic number (Z) [21]. Recently, Rabin et al. [22] synthesized Bi2S3 nanoplates which showed long vascular half-life and had considerable potential to achieve enhanced CT efficacy with a lower agent dose in the future clinical applications. Ai et al. [13] developed a facile strategy for the large-scale manufacture of Bi2S3 nanodots coated by oleic acid. After further surface modification by polyvinylpyrrolidone (PVP) through a versatile ligand exchange approach, these nanodots exhibited low cytotoxicity and high capabilities of angiography. On the other hand, the integration of diagnosis and treatment, namely theranostics, is expected to improve therapeutic efficacy and reduce side effects through more personalized therapies for various diseases [23]. Fortunately, nanoplatforms which can integrate imaging moieties and therapeutic species in flexible ways have enjoyed broad attention in cancer diagnosis and treatment in the past decade [24]. Among diverse investigations, imaging-guided photothermal therapy (PTT) has been reported extensively and gained high recognition [25,26], because near-infrared (NIR) laser induced photothermal ablation causes minimal invasion and harm to normal tissues [27,28]. In the light of broad NIR absorption, high photothermal conversion efficiency (PCE), low cost, good photostability and excellent biocompatibility, copper State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China Corresponding author (email: ) * . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 © Science China Press and Springer-Verlag Berlin Heidelberg 2017 ARTICLES . . . . . . . . . . . . . . . . . . . . . . . . . SCIENCE CHINA Materials Ultrasonication CT Tumor Cu1.94S Bi2S3 PTT PSIOAm Scheme 1 Schematic illustration for the fabrication and CT-guided PTT of the Cu1.94S-Bi2S3@PSIOAm multifunctional nanocomposites. chalcogenides (Cu2−xS) have become a type of promising candidate to meet severe demands of photothermal ablation [29–32]. Most recently, our group has reported the synthesis of ultrahigh 19F loaded Cu1.75S nanoprobes with small particle size (average size ~21 nm) for simultaneous19F magnetic resonance imaging (MRI) and PTT [33,34]. As for CT imaging-guided PTT [35,36], although much efforts have recently been concentrated on pursuing nanomaterials with not only the capacity of photothermal conversion but also CT imaging responses, some challenges remain to be addressed. For example, WO3−x and gold nanorods possess both NIR and CT responses [12,23], but the NIR response resulted from oxygen vacancies on the surface of WO3−x is easy to disappear with oxidization happened in the ambient environment; and due to the “melting effect”, the NIR absorbance peak and thus photothermal effects of gold nanorods will diminish after a long period of laser irradiation [37–39]. Additionally, Bi2S3 and Cu-Bi-S ternary nanocrystals such as Cu3BiS3 have been reported for dual-functional CT imaging and PTT [19,36,40]. However, the exploration and construction of ternary Cu-Bi-S nanomaterials with both strong NIR absorption and CT response is very limited because of their complicated stoichiometry and difficult preparation [36,40]. NIR response of these materials is highly sensitive to crystalline phase, size, morphology, and bandgap engineering. When doping with high proportion of Bi, the crystallinity of Cu-Bi-S nanostructures will be affected, thus decreases their photothermal efficacy; while small doping amount of Bi will then lead to the loss of CT imaging response [41–43]. Therefore, it is still a challenge to fabricate the multifunctional nanocomposites (NCs) possessing not only high CT signal but also strong photothermal efficiency. Here we present a facile and general strategy to fabricate multifunctional NCs by encapsulating both Cu1.94S and Bi2S3 nanocrystals into a biocompatible oleylamine functionalized poly-succinimide (PSIOAm) matrix with size of ~85 nm (Scheme 1) [44]. The definite structure of PSIOAm is shown in Fig. S1. The amount of Cu (...truncated)