Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, th...Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, the drug is a hydrophobic drug that is poorly soluble in water, and the mate is an amphiphilic small molecule (SMA) that has both hydrophilic and lipophilic properties. We proposed that the hydrophobic drug could co-assemble with a suitable SMA on a nanoscale without additive agents. The proof-ofconcept methodology and results were presented to support our hypothesis. We selected five hydrophobic drugs and more than ten amphiphilic small molecules to construct a library. Through molecular dynamic simulation and quantum chemistry computation,we speculated that the formation of nanoassemblies was related to the binding energy of the drug-mate, and the drug-mate interaction must overcome drug-drug interaction.Furthermore, the obtained SF/VECOONa nanoassemblieswas selected as a model, which had an ultra-high drug loading content (46%), improved pharmacokinetics, increased bioavailability, and enhanced therapeutic efficacy. In summary, the drug-mate strategy is an essential resource to design exact SMA for many hydrophobic drugs and provides a reference for the design of a carrier-free drug delivery system.展开更多
Background：Candida albicans （C.albicans） can become a pathogen causing superficial as well as life-threatening systemic infections,especially in immunocompromised patients.Many phenotypic attributes contribute to i...Background：Candida albicans （C.albicans） can become a pathogen causing superficial as well as life-threatening systemic infections,especially in immunocompromised patients.Many phenotypic attributes contribute to its capacity to colonize human organs.In our study,93 C.albicans isolates from patients of various candidiasis in a hospital of China were surveyed.We aimed to investigate the white-opaque （WO） switching competence,drug sensitivity,and virulence of mating type-like （MTL） a/α isolates.Methods：Internal transcribed spacer （ITS） gene and the MTL configuration were detected in all the isolates by reverse transcription-polymerase chain reaction.White/opaque phenotype and doubling time of cell growth were determined.The minimum inhibitory concentrations of antifungal agent were measured using broth microdilution method.Results：Sixty-four isolates （69.6%） were classified to serotype A,19 （20.6%） to serotype B,and 9 （9.8%） to serotype C.Moreover,phylogenetic analysis showed that these isolates were divided into four different subgroups of ITS genotypes.Most of our clinical isolates were MTLa/α type,while 6.8% remained MTLa or MTLα type.The frequency of opaque phenotype was 71.0% （66 isolates）.Following the guidelines of Clinical and Laboratory Standards Institute M27-A3,all isolates were susceptible to caspofungin and a few （0.6-3.2%） of them showed resistance against amphotericin B,flucytosine,fluconazole,itraconazole,and voriconazole.Conclusions：From these analyses,there were comparatively more C.albicans strains classified into serotype B,and the frequency of opaque phase strains was significant in the clinical isolates from China.Genetic,phenotypic,or drug susceptibility patterns were not significantly different from previous studies.MTLa/α isolates could also undergo WO switching which facilitates their survival.展开更多
基金supported by the National Natural Science Foundation of China (grant numbers:81974498)Natural Science Foundation of Shandong Province (grant numbers:ZR2019BH079)。
文摘Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, the drug is a hydrophobic drug that is poorly soluble in water, and the mate is an amphiphilic small molecule (SMA) that has both hydrophilic and lipophilic properties. We proposed that the hydrophobic drug could co-assemble with a suitable SMA on a nanoscale without additive agents. The proof-ofconcept methodology and results were presented to support our hypothesis. We selected five hydrophobic drugs and more than ten amphiphilic small molecules to construct a library. Through molecular dynamic simulation and quantum chemistry computation,we speculated that the formation of nanoassemblies was related to the binding energy of the drug-mate, and the drug-mate interaction must overcome drug-drug interaction.Furthermore, the obtained SF/VECOONa nanoassemblieswas selected as a model, which had an ultra-high drug loading content (46%), improved pharmacokinetics, increased bioavailability, and enhanced therapeutic efficacy. In summary, the drug-mate strategy is an essential resource to design exact SMA for many hydrophobic drugs and provides a reference for the design of a carrier-free drug delivery system.
文摘Background：Candida albicans （C.albicans） can become a pathogen causing superficial as well as life-threatening systemic infections,especially in immunocompromised patients.Many phenotypic attributes contribute to its capacity to colonize human organs.In our study,93 C.albicans isolates from patients of various candidiasis in a hospital of China were surveyed.We aimed to investigate the white-opaque （WO） switching competence,drug sensitivity,and virulence of mating type-like （MTL） a/α isolates.Methods：Internal transcribed spacer （ITS） gene and the MTL configuration were detected in all the isolates by reverse transcription-polymerase chain reaction.White/opaque phenotype and doubling time of cell growth were determined.The minimum inhibitory concentrations of antifungal agent were measured using broth microdilution method.Results：Sixty-four isolates （69.6%） were classified to serotype A,19 （20.6%） to serotype B,and 9 （9.8%） to serotype C.Moreover,phylogenetic analysis showed that these isolates were divided into four different subgroups of ITS genotypes.Most of our clinical isolates were MTLa/α type,while 6.8% remained MTLa or MTLα type.The frequency of opaque phenotype was 71.0% （66 isolates）.Following the guidelines of Clinical and Laboratory Standards Institute M27-A3,all isolates were susceptible to caspofungin and a few （0.6-3.2%） of them showed resistance against amphotericin B,flucytosine,fluconazole,itraconazole,and voriconazole.Conclusions：From these analyses,there were comparatively more C.albicans strains classified into serotype B,and the frequency of opaque phase strains was significant in the clinical isolates from China.Genetic,phenotypic,or drug susceptibility patterns were not significantly different from previous studies.MTLa/α isolates could also undergo WO switching which facilitates their survival.
