Bright, Magnetic NIR-II Quantum Dot Probe for Sensitive Dual-Modality Imaging and Intensive Combination Therapy of Cancer

Abstract

Improving the effectiveness of cancer therapy will require tools that enable more specific cancer targeting and improved tumor visualization. Theranostics have the potential for improving cancer care because of their ability to serve as both diagnostics and therapeutics; however, their diagnostic potential is often limited by tissue-associated light absorption and scattering. Herein, we develop CuInSe2@ZnS:Mn quantum dots (QDs) with intrinsic multifunctionality that both enable the accurate localization of small metastases and act as potent tumor ablation agents. By leveraging the growth kinetics of a ZnS shell on a biocompatible CuInSe2 core, Mn doping, and folic acid functionalization, we produce biocompatible QDs with high near-infrared (NIR)-II fluorescence efficiency up to 31.2%, high contrast on magnetic resonance imaging (MRI), and preferential distribution in 4T1 breast cancer tumors. MRI-enabled contrast of these nanoprobes is sufficient to timely identify small metastases in the lungs, which is critically important for preventing cancer spreading and recurrence. Further, exciting tumor-resident QDs with NIR light produces both fluorescence for tumor visualization through radiative recombination pathways as well as heat and radicals through nonradiative recombination pathways that kill cancer cells and initiate an anticancer immune response, which eliminates tumor and prevents tumor regrowth in 80% of mice.

Semiconductor Nanocrystals Emitting in the Second Near‐Infrared Window: Optical Properties and Application in Biomedical Imaging

“…NIR-II fluorescence can achieve good imaging resolution even for deep tissue penetration, which makes it promising for providing information with high physiological and pathological relevance. [14,24,38] In 2009, the use of light-emitting single-wall carbon nanotubes to perform in vivo NIR-II imaging of tumor vessels beneath the skin of mice constituted one of the first steps in making use of NIR-II window for biological imaging. [24] Pioneering SNC-based NIR-II fluorescence imaging studies were based on Ag 2 S SNCs, [47,83] and demonstrated high signal-to-noise ratio for in vivo imaging.…”

“…[179] Alongside with developments of imaging instrumentation for efficiently collecting NIR-II emission signals, NIR-II emitting SNCs were used to portray structures of living tissues, including vascular system, lymphatic system, and tumors. [12,13,38,46] By using PEGylated Ag 2 S SNCs with a long blood circulation time as the contrast agent, peripheral vasculature (≈100 µm in size) was visualized in vivo at a micro meter-scale resolution, which holds great potential for real-time imaging of those structures when dealing with vascular-related diseases. [46] In the same study, PEGylated Ag 2 S SNCs were also used for imaging lymphatic vessels (≈100 µm in size) and lymph nodes (≈950 µm in size), and the clarity and penetration depth were significantly improved compared with ICG dye, a standard contrast agent for clinically guided sentinel-lymph-node resection, which can help to guide the surgeries more precisely for their identification and dissection.…”

“…Breaking limitations of single imaging modality, multimodal imaging is a highly desirable approach for precise diagnostics of diseases, as it integrates advantages of different imaging modalities. [22,38,152,192] Using magnetic/fluorescent SNC-based materials has been a popular approach for the magnetic resonance imaging (MRI) combined with fluorescence imaging. [152] There are several strategies to impart magnetic properties into SNCs: conjugating magnetic chelates onto SNCs, doping SNCs with magnetic metal ions, or encapsulating magnetic particles and SNCs within a composite material.…”

“…The disadvantage of this approach was that magnetic Gd chelates may become unreliable in some physiological environments because of their relatively weak coordination force. [152,158] In contrast, intrinsically magnetic SNCs, which combine both magnetic and fluorescence properties within one and the same nanoparticle, exhibited more reliable properties resisting external disturbances, as demonstrated for Mn-doped CuInS 2 /ZnS [158] and Mn-doped CuInSe 2 /ZnS [38] SNCs used as dual-modal imaging probes. Paramagnetic Mn 2+ ions were doped into the ZnS shell rather than into core SNCs in order to avoid the PL quenching effect by Mn.…”

“…Currently, NIR-II SNCs are represented by I-VI (Ag 2 S, Ag 2 Se, Ag 2 Te), II-VI (CdTe, HgTe), IV-VI (PbS, PbSe, PbTe), and III-V (InP, InAs) binary compound semiconductors, as well as I-III-V (CuInSe 2 , AgInSe 2 ) ternary SNCs. [11,38,40] However, many of them contain highly toxic elements such as Cd, Hg, and Pb, which excludes their clinical use due to severe biosafety concerns. Thus, there is a high demand on biocompatible SNCs, Development of fluorophores with emission in the so-called second near-infrared window (NIR-II, 1000-1700 nm) represents an active area of the contemporary research.…”