RESUMO
Chemoresistance remains a significant challenge for effective breast cancer treatment which leads to cancer recurrence. CRISPR-directed gene editing becomes a powerful tool to reduce chemoresistance by reprogramming the tumor microenvironment. Previous research has revealed that Chinese herbal extracts have significant potential to overcome tumor chemoresistance. However, the therapeutic efficacy is often limited due to their poor tumor targeting and in vivo durability. Here we have developed a tumor microenvironment responsive nanoplatform (H-MnO2(ISL + DOX)-PTPN2@HA, M(I + D)PH) for nano-herb and CRISPR codelivery to reduce chemoresistance. Synergistic tumor inhibitory effects were achieved by the treatment of isoliquiritigenin (ISL) with doxorubicin (DOX), which were enhanced by CRISPR-based gene editing to target protein tyrosine phosphatase non-receptor type 2 (PTPN2) to initiate long-term immunotherapy. Efficient PTPN2 depletion was observed after treatment with M(I + D)PH nanoparticles, which resulted in the recruitment of intratumoral infiltrating lymphocytes and an increase of proinflammatory cytokines in the tumor tissue. Overall, our nanoparticle platform provides a diverse technique for accomplishing synergistic chemotherapy and immunotherapy, which offers an effective treatment alternative for malignant neoplasms.
Assuntos
Doxorrubicina , Imunoterapia , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Animais , Imunoterapia/métodos , Doxorrubicina/farmacologia , Humanos , Camundongos , Linhagem Celular Tumoral , Feminino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Edição de Genes/métodos , Sistemas CRISPR-Cas , Compostos de Manganês/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Antineoplásicos/farmacologia , Antineoplásicos/química , ÓxidosRESUMO
Continued collecting efforts at the Jiulong National Wetland Park, Zhejiang, East China revealed two additional species of the ant-loving beetle subfamily Pselaphinae (Coleoptera: Staphylinidae): Trisiniotus jiulong sp. nov. and Arthromelodes lianghongbini sp. nov. Both new species are diagnosed, described, and their important characters are illustrated.
Assuntos
Formigas , Besouros , Animais , Áreas Alagadas , Distribuição Animal , ChinaRESUMO
Circular RNAs (circRNAs), a group of non-coding RNA characterized by the presence of covalent bonds linking 3' and 5' ends, act as miRNA sponges to participate in the tumorigenesis. Being stable, conserved and cell- or tissue-specific, circRNAs have shown their potentials as molecular markers for cancer. Convenient and noninvasive approaches may be developed based on the roles of circRNAs to diagnose or predict the prognosis of tumors. Although most of the potential mechanisms are not entirely clear, circRNAs have shown a universal and critical role in regulating cellular processes of cancers. This review summarized the classification, formation, characteristics, detection, and biological functions of circRNAs. We proposed the possibility of using circRNAs as biomarkers for cancer diagnosis, treatment and prognosis.