Engineering Sonosensitizer-Derived Nanotheranostics for Augmented Sonodynamic Therapy.

Sonodynamic therapy (SDT), featuring noninvasive, deeper penetration, low cost, and repeatability, is a promising therapy approach for deep-seated tumors. However, the general or only utilization of SDT shows low efficiency and unsatisfactory treatment outcomes due to the complicated tumor microenvironment (TME) and SDT process. To circumvent the issues, three feasible approaches for enhancing SDT-based therapeutic effects, including sonosensitizer optimization, strategies for conquering hypoxia TME, and combinational therapy are summarized, with a particular focus on the combination therapy of SDT with other therapy modalities, including chemodynamic therapy, photodynamic therapy, photothermal therapy, chemotherapy, starvation therapy, gas therapy, and immunotherapy. In the end, the current challenges in SDT-based therapy on tumors are discussed and feasible approaches for enhanced therapeutic effects are provided. It is envisioned that this review will provide new insight into the strategic design of high-efficiency sonosensitizer-derived nanotheranostics, thereby augmenting SDT and accelerating the potential clinical transformation.

Identification of key gene networks controlling vernalization development characteristics of Isatis indigotica by full-length transcriptomes and gene expression profiles.

Isatis indigotica Fort., as a common Chinese medicinal raw material, will lose its medicinal value if it blooms early, so it is highly valuable to clarify the induction mechanism of the vernalization of I. indigotica at low temperature. In this study, the concentrations of soluble sugar, proline, glutathione and zeatin in two germplasms of I. indigotica with different degrees of low temperature tolerance (Y1 and Y2) were determined at 10 days, 20 days and 30 days of low-temperature treatment, and the full-length transcriptome of 24 samples was sequenced by Nanopore sequencing with Oxford Nanopore Technologies (ONT). After that, the data of transcripts involved in the vernalization of I. indigotica at low temperature were obtained, and these transcripts were identified using weighted gene co-expression network analysis (WGCNA). The results revealed the massive accumulation of soluble sugar and proline in Y1 and Y2 after low temperature induction. A total of 18,385 new transcripts, 6168 transcription factors and 470 lncRNAs were obtained. Differential expression analysis showed that gibberellin, flavonoids, fatty acids and some processes related to low temperature response were significantly enriched. Eight key transcripts were identified by WGCNA, among which ONT.14640.1, ONT.9119.1, ONT.13080.2 and ONT.16007.1 encodes a flavonoid transporter, 9-cis-epoxycarotenoid dioxygenase 3 (NCED3), growth factor gene and L-aspartate oxidase in plants, respectively. It indicated that secondary metabolites such as hormones and flavonoids play an important role in the vernalization of I. indigotica. qRT-PCR proved the reliability of transcriptome results. These results provide important insights on the low-temperature vernalization of I. indigotica, and provide a research basis for analyzing the vernalization mechanism of I. indigotica. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01110-2.

A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.

A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I. The total yield can reach 71%. This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues. The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.