CuS Nanodots with Ultrahigh Efficient Renal Clearance for Positron Emission Tomography Imaging and Image-Guided Photothermal Therapy

Abstract

Translation of nanoparticles (NPs) into clinical practice has been limited by toxic effects induced by nonspecific accumulation of NPs in healthy organs after systemic administration. The ideal NPs should accumulate in the target site, carry out their function, and then ultimately be eliminated from the body. Here, we show a single-compartment, multifunctional ultrasmall copper sulfide nanodot (CuS ND) that is rapidly cleared from the body. These CuS NDs have a hydrodynamic diameter of <6 nm, can efficiently absorb near-infrared light for photothermal ablation therapy, and stably incorporate the copper-64 radioisotope for noninvasive positron emission tomography (PET). Importantly, ~95% of CuS NDs are excreted intact through the renal–urinary system within 24 h with minimal retention in the liver and the spleen. The ultrasmall CuS NDs accumulate in 4T1 tumors in Balb/c mice, as monitored by PET imaging, and mediate tumor ablation when combined with near-infrared light irradiation. As a first example of PET-visible, renal-clearable inorganic nanomaterials with peak absorption in the near-infrared region, CuS NDs represent a robust platform for cancer imaging and therapy.

68 Ga-Radiolabeled AGuIX Nanoparticles as Dual-Modality Imaging Agents for PET/MRI-Guided Radiation Therapy

“…In the tumor environment, a similar aggregation can occur that can explain the nondegradation of the NPs observed in the tumor. The results presented here show moderate tumor accumulation via passive targeting, which are comparable to results described by other groups in the literature [28][29][30][31]. However, while tumor uptake is quite similar, uptake in the RES organs is much higher in those studies, which could be problematic for future clinical translation.…”

BSA-assisted synthesis of ultrasmall gallic acid&ndash;Fe(III) coordination polymer nanoparticles for cancer theranostics

“…The size of these NPs is thought to be beneficial for biological applications, given that ultrasmall NPs are easily excreted from the human body. 7 Compared with previous data (in which the average NP diameter was Figures 1B and S6), the mean hydrodynamic diameter of GA-Fe@BSA NPs was 8.8 nm, which was slightly larger than results observed with atomic force microscopy. This phenomenon has been explained in a previous study in which the hydrodynamic diameter readings of BSA-coated NPs were slightly larger due to the strong hydrophilicity of BSA.…”

“…2,3 The development of nanotheranostic agents can be classified into two categories: inorganic and organic. 4 Inorganic nanotheranostic agents, including noble metals, 5,6 semiconductor NPs, 7,8 and carbon materials, [9][10][11] are studied extensively, as they are highly stable and have multifunctional properties. However, inorganic materials do not degrade, and long-term retention in the body limits their clinical use for cancer treatments, 12 since agents must completely clear the body within a reasonable period to receive regulatory approval from the US Food and Drug Administration (FDA).…”

Degradable Molybdenum Oxide Nanosheets with Rapid Clearance and Efficient Tumor Homing Capabilities as a Therapeutic Nanoplatform

“…[5c, 6,8] The main strategy is to synthesize ultrasmall nanoparticles and functionalize them with athin layer of hydrophilic coating, so as to minimize their hydrodynamic sizes in the physiological environment to enable rapid renal filtration.…”

“…[5c, 6,8] However, those ultra-small nanoparticles would behave somewhat like small molecules:their rapid renal excretion on the other hand would lead to the shortened blood circulation half-lives and weakened EPR effect, resulting in reduced tumor accumulation and retention. [5c,6] Ideally,i tw ould be the best to develop inorganic nanoagents which can be quickly excreted from the normal organs of the body,w hile being able to effectively accumulate and retain in tumors,u pon systemic administration.…”