Drug-induced resistance, or tolerance, is an emerging yet poorly understood failure of anticancer therapy. The interplay between drug-tolerant cancer cells and innate immunity within the tumor, the consequence on tumor growth, and therapeutic strategies to address these challenges remain undescribed. Here, we elucidate the role of taxane-induced resistance on natural killer (NK) cell tumor immunity in triple-negative breast cancer (TNBC) and the design of spatiotemporally controlled nanomedicines, which boost therapeutic efficacy and invigorate “disabled” NK cells. Drug tolerance limited NK cell immune surveillance via drug-induced depletion of the NK-activating ligand receptor axis, NK group 2 member D, and MHC class I polypeptide-related sequence A, B. Systems biology supported by empirical evidence revealed the heat shock protein 90 (Hsp90) simultaneously controls immune surveillance and persistence of drug-treated tumor cells. On the basis of this evidence, we engineered a “chimeric” nanotherapeutic tool comprising taxanes and a cholesterol-tethered Hsp90 inhibitor, radicicol, which targets the tumor, reduces tolerance, and optimally reprimes NK cells via prolonged induction of NK-activating ligand receptors via temporal control of drug release in vitro and in vivo. A human ex vivo TNBC model confirmed the importance of NK cells in drug-induced death under pressure of clinically approved agents. These findings highlight a convergence between drug-induced resistance, the tumor immune contexture, and engineered approaches that consider the tumor and microenvironment to improve the success of combinatorial therapy. Significance: This study uncovers a molecular mechanism linking drug-induced resistance and tumor immunity and provides novel engineered solutions that target these mechanisms in the tumor and improve immunity, thus mitigating off-target effects.
Viral diseases are extremely widespread infections caused by viruses. Amongst numerous other illnesses, viral infections have challenged human existence severely. Over the history of mankind, new viruses have emerged and presented us with new tests. The range of viral infections varies from familiar infectious diseases such as the common cold, flu, and warts to severe ailments such as AIDS, Ebola, and COVID-19. The world has been racing to find an effective cure for the newly evolving viruses. Toxic effects, non-selectivity, drug resistance, and high price are the most common complications of conventional treatment procedures. Nature is a marvelous source of phytoconstituents with incredible varieties of biological activities. By tradition, medicinal plants have been utilized for the treatment of countless infectious diseases worldwide, some of which contain a broad spectrum of activities. Modern drug discovery and development techniques offer highly efficient separation techniques, inauguration of vector-based schemes where the original infectious virus is cloned to the non-infectious one for antiviral screening targets. The objective of the review was to gather available data on 20 both cultivated and native plants of Asia giving antiviral activities and provide comprehensive information on the phytochemical analysis of the plants and potential antiviral compounds isolated from these plants.
Mucuna pruriens is a tropical legume native to Africa, India and Bangladesh and is widely cultivated in tropical countries. In this study, a crude methanolic extract of the leaves of M. pruriens was investigated for its chemical constituents and to explore the phenolic and flavonoid content, antioxidant, cytotoxic and antimicrobial activities using established protocols. From the ethyl acetate soluble fraction of the crude methanol extract, three known compounds namely ferulic acid (1), 2-(5-methoxy-1-benzofuran-3-yl)-N-ethylethanamine (2) and stizolamine (3) were isolated and their structures were elucidated by the analysis of NMR spectral data. The crude extract was found to possess phenolic content of 216.16 μg/g whereas the concentration of flavonoid was found to 214.8 μg/g expressed in quercetin standard. Free radicals generated through DPPH were neutralized by crude methanolic extract and the IC50 value was obtained as 19.63 μg/ml. Regression analysis during brine shrimp lethality test enumerated LC50 value of crude methanolic extract at 10.72 μg/ml and was significant compared to the positive standard. The crude methanolic extract of leaf of M. pruriens did not show any significant antimicrobial activity against the organisms used in our test. Dhaka Univ. J. Pharm. Sci. 20(1): 103-109, 2021 (June)
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