A prodrug is bioreversible medication that is specifically converted to the active drugs by enzymes overexpressed in the tumor microenvironment, which can considerably reduce the chemotherapy-induced side effects. However, prodrug strategies usually have low antitumor efficacy compared to free drugs by delayed drug release. This is because they need time to be activated by enzymatic cleavage and they also cannot be fully recovered to the active drugs. Therefore, highly potent anticancer drug should be considered to expect a sufficient antitumor efficacy. Herein, we propose tumor-specific monomethyl auristatin E (MMAE) prodrug nanoparticles for safe and effective chemotherapy. The cathepsin B-specific cleavable FRRG peptide and MMAE are chemically conjugated via one-step simple synthetic chemistry. The resulting FRRG-MMAE molecules form stable nanoparticles without any additional carrier materials by hydrophobic interaction-derived aggregations. The FRRG-MMAE nanoparticles efficiently accumulate within the tumor tissues owing to the enhanced permeability and retention (EPR) effect and inhibit the tubulin polymerization by releasing free MMAE in the cathepsin B-overexpressed tumor cells. In contrast, FRRG-MMAE nanoparticles maintain a non-toxic inactive state in the normal tissues owing to innately low cathepsin B expression, thereby reducing MMAE-related severe toxicity. Collectively, this study provides a promising approach for safe and effective chemotherapy via MMAE-based prodrug nanoparticles, which may open new avenues for advanced drug design for translational nanomedicine.

Gold nanoparticles (AuNPs) with various sizes and morphologies have been extensively investigated for effective photothermal therapy (PTT) against multiple cancer types. However, a highly dynamic and complex tumor microenvironment (TME) considerably reduces the efficacy of PTT by limiting deep tumor penetration of AuNPs. Herein, we propose a mesenchymal stem cell (MSC)-mediated deep tumor delivery of gold nanorod (AuNR) for a potent PTT. First, MSCs are treated with tetraacylated N-azidomannosamine (Ac₄ManNAz) to introduce modifiable azide (N₃) groups on the cell surface via metabolic glycoengineering. Then, AuNRs modified with bio-orthogonal click molecules of bicyclo[6.1.0]nonyne (AuNR@BCN) are chemically conjugated to the N₃ groups on the MSC surface by copper-free click chemistry reaction, resulting in AuNR@MSCs. In cultured MSCs, the appropriate condition to incorporate the AuNR into the MSCs is optimized; in addition, the photothermal efficiency of AuNR-MSCs under light irradiation are assessed, showing efficient heat generation in vitro. In colon tumor-bearing mice, intravenously injected AuNR@MSCs efficiently accumulate within the tumor tissues by allowing deep tissue penetration owing to the tumor homing effect by natural tumor tropism of AuNR@MSCs. Upon localized light irradiation, the AuNR@MSCs significantly inhibit colon tumor growth by the enhanced photothermal effect compared to conventional AuNRs. Collectively, this study shows a promising approach of MSCs-mediated deep tumor delivery of AuNR for effective PTT.

Introduction: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has become increasingly popular. Several reports have emphasized the safety and efficacy of this new approach. However, there is no report on functional voice outcomes, including voice pitch change after TOETVA. Methods: The functional voice outcomes of patients undergoing TOETVA were compared with those of patients undergoing conventional thyroidectomy. A total of 82 consecutive patients were included in the study: 44 underwent thyroid lobectomy via TOETVA (transoral group) and 38 underwent thyroid lobectomy via the classic cervical approach (open group). Thyroidectomy-related voice questionnaire (TVQ), perceptual voice analysis, fiberoptic laryngoscopic and videolaryngostroboscopic examinations, and acoustic analysis were carried out before and one month after surgery. The changes in these values after surgery and the differences between the transoral and open groups were analyzed. Results: We found no significant postoperative change in voice workups in either group. The mean high pitch decreased (from 367.91 ± 120.98 to 325.80 ± 100.86 Hz, p = 0.069) in the transoral group, but statistical significance was not attained. Clinically significant changes in pitch (postoperative change in speaking fundamental frequency, ΔSFF ≥ 12) after surgery were evident in seven (15.91%) patients in the transoral group and eight (21.05%) patients in the open group without significant difference (p = 0.579). Conclusions: This is the first study to assess functional voice outcomes (including pitch) after TOETVA compared with conventional open surgery. TOETVA was associated with good voice outcomes without any significant drop in pitch.

Potassium-Titanyl-Phosphate (KTP) Laser Photocoagulation Combined with Resection Using an Ultrasonic Scalpel for Pharyngolaryngeal Hemangioma via a Transoral Approach: Case Report and Literature Review - Article abstract #931042

It had been observed that some cystic nodules change morphologically with ultrasonographic (US) features suspicious for malignancy. The aim of this study was to evaluate the US characteristics of benign cystic nodules mimicking papillary thyroid carcinoma (PTC) during interval changes. Between January 2009 and October 2009, 26 patients with benign cystic nodules showing marked hypoechogenicity in US during the follow-up period were enrolled. During the same period, 38 patients with marked hypoechogenicity in US were enrolled for the PTC group. We evaluated the differences in US characteristics between the 2 groups. Nodule size, margin, echogenic dot and vascularity were not significantly different between the 2 groups. Nodule shape was significantly different between the 2 groups with a lower prevalence of taller than wide in the benign cystic group (11.5% vs. 39.5%, P=0.022). Other coexisting cystic nodules were more frequently observed in benign cystic group (48.3% vs. 5.3%, P=0.001). If echogenic dot was detected in benign cystic nodule, it was more than 1 mm in size without posterior acoustic shadowing unlike echogenic dots in the PTC group. In conclusion, some of the benign cystic nodules may have suspicious malignant features on US during interval changes. A careful assessment of US findings and a previous history may be of value in discriminating them from PTC.

No TH, et al. Infect Chemother. 2020 Dec;52(4):634-640. https://doi.org/10.3947/ic.2020.52.4.634