Yongdoo Choi

Accurate intraoperative localization of deep-seated lesions remains a major challenge in minimally invasive procedures such as laparoscopic and robotic surgeries. Current marking strategies—including ink tattooing and metallic clips—are limited by dye diffusion, or poor intraoperative visibility. To address these issues, we developed and evaluated four thermosensitive injectable hydrogel systems incorporating indocyanine green-human serum albumin (ICG-HSA) complexes: (1) hexanoyl glycol chitosan (HGC), (2) Pluronic F-127, (3) PCL–PEG–PCL, and (4) PLA–PEG–PLA. All hydrogel formulations exhibited sol–gel transitions at physiological temperatures, facilitating in situ dye entrapment and prolonged fluorescence retention. In vivo fluorescence imaging revealed that HGC and Pluronic F-127 hydrogels retained signals for up to five and two days, respectively. In contrast, polyester-based hydrogels (PCL–PEG–PCL and PLA–PEG–PLA) preserved fluorescence for up to 21–30 days. PLA–PEG–PLA showed the highest signal-to-background ratios and sustained intensity, while PCL–PEG–PCL also achieved long-term retention. These findings suggest that thermosensitive hydrogels incorporating ICG-HSA complexes represent promising tissue marker platforms for real-time, minimally invasive, and long-term fluorescence-guided lesion tracking.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are considered to be one of the most effective methods for treating cancer due to their noninvasive nature, high effectiveness, and fewer side effects compared to standard therapeutic modalities for cancer. However, conventional always-on types of PDT and PTT agents have basic drawbacks in their in vivo applications, which include the unwanted generation of strong fluorescence signals and phototoxicity in normal tissues, including blood vessels, when exposed to light, resulting in poor imaging contrast and unwanted phototoxicity. Here, we propose indocyanine green-loaded quenched nanoliposomes (Q-ICG-NLs) as an activatable nanotheranostics. Q-ICG-NLs showed significant quenching in near-infrared fluorescence emission and singlet oxygen generation upon light irradiation. The photothermal effect of Q-ICG-NLs was 1.3 times greater than free indocyanine green. Its fluorescence and singlet oxygen generation were largely restored when taken up into cancer cells, enabling the selective detection and phototherapy of cancer cells. These results suggest that Q-ICG-NLs can be effectively used for selective near-infrared fluorescence imaging and the subsequent image-guided PDT and PTT of cancers.

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various ratios. Sensitivity was assessed by the detection rate of null–homozygote (N–H) alleles at expected variant allelic fractions, while false positive (FP) errors were counted for unexpected alleles. Sensitivity was approximately 20% for in-house results from BB and CC and around 5% for AA. Dynamic Read Analysis for GENomics (DRAGEN) analyses identified 1.34 to 1.71 times more variants, detecting over 96% of in-house variants, with sensitivity for common variants increasing to 5%. In-house FP errors varied significantly among companies (up to 13.97 times), while DRAGEN minimized this variation. Despite DRAGEN showing higher FP errors for BB and CC, the increased sensitivity highlights the importance of effective bioinformatic conditions. We also assessed the potential effects of target enrichment and proposed optimal cutoff values for the read depth and variant allele fraction in WES. Optimizing bioinformatic analysis based on sensitivity and specificity from reference standards can enhance variant detection and improve the clinical utility of WES.

Accurate tumor localization is crucial for the success of minimally invasive surgery, as it minimizes the resection of normal tissues surrounding tumors. Traditional methods for marking gastrointestinal (GI) tumors, such as ink tattooing, intraoperative gastroscopy or colonoscopy, and placement of metal clips, have major drawbacks in their application in laparoscopic surgery. Therefore, the development of safe and easy-to-operate marking methods for accurate and real-time detection of GI tumors during laparoscopic surgery remains an ongoing challenge. Here, we propose a new fluorescent metal clip (MicBall800 clip) for noninvasive and precise fluorescence marking of GI tumors. First, we prepared a poly(methyl methacrylate) microball with small, multiple, and separated pores in its internal structure, and near-infrared fluorescence dye (IRDye800CW) and human serum albumin complex were loaded into the pores. This near-infrared-dye-loaded poly(methyl methacrylate) microball (MicBall800) was then coated onto the surface of the metal clips to produce a highly fluorescent MicBall800 clip. Safety and biocompatibility tests of the MicBall800 clip were conducted by the Korea Testing Certification Institute. The MicBall800 clip was evaluated in vivo using a porcine model. The MicBall800 clip passed safety and biocompatibility tests. The MicBall800 clip could be easily marked at the target sites without causing any side effects and was detected in real time during the laparoscopic operation. The data obtained from the safety and biocompatibility tests and the in vivo animal study indicate that the MicBall800 clip can be an important advancement in minimally invasive and precision surgery for GI cancers.

Purpose Poly(ethylene glycol) (PEG), a synthetic polymer known for its hydrophilicity and biocompatibility, has long been used in drug delivery systems to prevent non-specific protein adsorption and to extend the blood circulation time of drug carriers and protein drugs. However, PEG has several drawbacks including poor stability, accumulated toxicity, and immunogenicity induced by repeated injections. Recently, zwitterionic polymers, known for their super-hydrophilic and antifouling properties, have been considered excellent alternatives to PEG. In this study, we synthesized a new zwitterionic polymer from biocompatible sodium alginate and lysine. Methods Sodium alginate (Alg) was conjugated with lysine (Lys) using the EDC/sulfo-NHS chemistry to form a zwitterionic alginate derivative (Alg-Lys). The biocompatibility was evaluated using in vitro cellular assays and in vivo animal studies. After further conjugation of zwitterionic near-infrared (NIR) fluorescent dye ZW800, an in vivo NIR fluorescence imaging study was conducted to evaluate the ability of Alg-Lys to enhance blood circulation time. Results Characterization of Alg-Lys showed that the carboxylic acid groups in Alg were completely replaced by Lys molecules. No cytotoxic effects were observed in the in vitro cytotoxicity tests of Alg-Lys-treated cancer cells and normal cells. Serum biochemical analysis confirmed the biocompatibility of Alg-Lys. ZW800-conjugated Alg-Lys exhibited strong fluorescence signals throughout the body 24 h after intravenous injection, whereas ZW800-conjugated Alg was rapidly removed from the body. Conclusion The zwitterionic alginate derivative showed potential utility as a new delivery platform for imaging agents and drugs.

The activatable fluorescence probe Q-Atezol demonstrates great potential as an exceptional sensor for assessing PD-L1 expression in three-dimensional cell structures and for in vivo applications.

The efficacy of glioblastoma treatment is closely associated with complete tumor resection. However, conventional surgical techniques often result in incomplete removal, leading to poor prognosis. A major challenge is the accurate delineation of tumor margins from healthy tissues. Imaging-guided surgery, particularly using fluorescent probes, is a promising solution for intraoperative guidance. The recently developed ‘always-on’ types of targeted fluorescence probes generate signals irrespective of their presence in tumor cells or in blood circulation, hampering their effectiveness. Here, we propose a novel activatable fluorescence imaging probe, Q-cRGD, that targets glioma cells via the specific binding of the cyclic Arg-Gly Asp-containing pentapeptide (cRGD) to integrins. The Q-cRGD probe was synthesized by conjugating a near-infrared (NIR) dye to a tryptophan quencher via a disulfide linkage, including a cRGD-targeting ligand. This activatable probe remained inactive until the redox-responsive cleavage of the disulfide linkage occurred within the target cell. The zwitterionic nature of NIR dyes minimizes nonspecific interactions with serum proteins, thereby enhancing the tumor-to-background signal ratio (TBR). An in vivo fluorescence imaging study demonstrated a TBR value of 2.65 within 3 h of the intravenous injection of Q-cRGD, confirming its potential utility in imaging-guided brain cancer surgery.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have shown the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. Although additional in vivo studies are necessary, this study suggests that the combination therapy of abemaciclib and desipramine may represent a novel therapeutic approach for treating solid tumors.