Zhong Qing/Wang Weiwei, School of Basic Medical Sciences, et al. reported a new spray-type contrast agent that rapidly identifies tumor boundaries

Biomedical imaging plays a very important role
in cancer diagnosis, intraoperative guidance, and postoperative evaluation.
Fluorescence imaging has attracted widespread attention
in biomedical research due to its low cost, fast feedback, high sensitivity, and non-hazardous radiation.

The excitation light used in conventional optical imaging is usually visible light, which is greatly attenuated
as it penetrates biological tissue due to tissue absorption and light scattering.
The use of near-infrared (650~900nm) excitation light can achieve deeper tissue penetration and lower tissue autofluorescence, so as to obtain deep tissue imaging
with high signal-to-background ratio (SBR).

The FDA approved Cytalux (pafolacianine sodium; Formerly known as OTL38) in adult ovarian cancer patients as an adjunct to intraoperative identification of malignant lesions
.
Cytalux is used as a near-infrared diagnostic agent and is administered
intravenously before surgery.
Because ovarian cancer typically results in high expression of folate receptors in cell membranes, Cytalux specifically binds to folate receptors when it enters the body and glows under near-infrared irradiation, helping surgeons pinpoint and remove cancerous tissue
.
As a result, near-infrared fluorescent contrast agents targeting tumors have become an emerging hotspot
in the field of new drug research and development in the future.

Recently, Zhong Qing and Wang Weiwei's research group of Shanghai Jiao Tong University School of Medicine, together with Xu Bin and Chen Qi's research group of the Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, and Chen Lu's research group of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, published an article
entitled "A Novel Spraying Nanoprobe for Renal Cell Carcinoma in Humans" in Life Medicine 。 This paper reports a simple, efficient and well-designed tumor tissue imaging method that can achieve intraoperative real-time tumor imaging
by simply spraying the synthetic nanoparticle aqueous solution directly onto the surface of the tumor tissue.

In this paper, the nanoparticle S-4-NP
self-assembled with near-infrared hypoxia targeting dye (Dye) and anionic surfactant (Surfactin) is reported.
S-4-NP is self-quenching outside the cell due to the presence of its nanostructure
.
When S-4-NP comes into contact with tumor cells, Dye can specifically identify organic anion-transporting polypeptides (OATPs) on the cell membrane and then release them from the nanoparticles into the cell
.
In cells, free Dye is activated and can be excited by near-infrared light to label tumor cells (Figure 1).

Fig.
1 Validation of mouse tumorigenic model

Immediately after removing the tumor from the tumor-bearing mouse, the S-4-NP solution is sprayed onto
the tumor tissue.
NIR imaging
of samples is performed 3 min, 6 min, 9 min and 12 min after spraying.
The strength of the near-infrared signal also increased significantly (>2 times) within 3~12min, indicating that its stability is good
.

Fig.
2 Verification of radical nephrectomy

This article focuses on the application of S-4-NP in clinical renal cancer resection surgery (Figure 2).

Nephron-sparing surgery (NSS) is the most important method of treatment for early kidney cancer (RCC), aiming to cure the tumor while maximizing kidney function
.
However, positive surgical margins (PSMs) after renal surgery cannot be completely avoided, and are associated with
local recurrence and reduced survival.
At present, there is still a lack of rapid response, non-toxic tumor-specific contrast agent detection margins
.

During surgery, S-4-NP can be directly sprayed with the isolated tumor tissue section, and the tumor tissue can be clearly identified within 3 minutes through near-infrared imaging, thereby helping clinical surgeons quickly distinguish the boundary between tumor tissue and normal tissue, and judge the surgical margin (see Figure 3 for the complete imaging video
).

Figure 3

Kidney-sparing surgery is the surgical technique
of choice for the treatment of early-stage kidney tumors.
However, the issue of positive margins is still a concern, and in the past, intraoperative surgeons were usually relied on to visually determine tumor margins
.
Confirmation of the suspected site requires a longer wait for frozen sections or final paraffin sections
.
The imaging method is fast and efficient, so that surgeons can take remedial measures immediately after finding positive margins, which can effectively shorten the operation time, improve the prognosis of patients, and reduce the tumor recurrence rate, which has important clinical transformation significance
.