Shruti Bhatt, Subrata Dasgupta, Chiging Tupe, Cherish Prashar, Utpal Adhikari, Kailash C Pandey*, Suman Kundu and Soumyananda Chakraborti*,
{"title":"基于铁蛋白的蛋白笼抗疟输送:向开发抗疟疾智能疗法迈出的一步。","authors":"Shruti Bhatt, Subrata Dasgupta, Chiging Tupe, Cherish Prashar, Utpal Adhikari, Kailash C Pandey*, Suman Kundu and Soumyananda Chakraborti*, ","doi":"10.1021/acs.biochem.3c00692","DOIUrl":null,"url":null,"abstract":"<p >Over the past two decades, the utilization of protein cages has witnessed exponential growth driven by their extensive applications in biotechnology and therapeutics. In the context of the recent Covid-19 pandemic, protein-cage-based scaffolds played a pivotal role in vaccine development. Beyond vaccines, these protein cages have proven valuable in diverse drug delivery applications thanks to their distinctive architecture and structural stability. Among the various types of protein cages, ferritin-based cages have taken the lead in drug delivery applications. This is primarily attributed to their ease of production, exceptional thermal stability, and nontoxic nature. While ferritin-based cages are commonly employed in anticancer drug delivery and contrast agent delivery, their efficacy in malarial drug delivery had not been explored until this study. In this investigation, several antimalarial drugs were encapsulated within horse spleen ferritin, and the binding and loading processes were validated through both experimental and computational techniques. The data unequivocally demonstrate the facile incorporation of antimalarial drugs into ferritin without disrupting its three-dimensional structure. Computational docking and molecular dynamics simulations were employed to pinpoint the precise location of the drug binding site within ferritin. Subsequent efficacy testing on <i>Plasmodium</i> revealed that the developed nanoconjugate, comprising the drug–ferritin conjugate, exhibited significant effectiveness in eradicating the parasite. In conclusion, the findings strongly indicate that ferritin-based carrier systems hold tremendous promise for the future of antimalarial drug delivery, offering high selectivity and limited side effects.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antimalarial Delivery with a Ferritin-Based Protein Cage: A Step toward Developing Smart Therapeutics against Malaria\",\"authors\":\"Shruti Bhatt, Subrata Dasgupta, Chiging Tupe, Cherish Prashar, Utpal Adhikari, Kailash C Pandey*, Suman Kundu and Soumyananda Chakraborti*, \",\"doi\":\"10.1021/acs.biochem.3c00692\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Over the past two decades, the utilization of protein cages has witnessed exponential growth driven by their extensive applications in biotechnology and therapeutics. In the context of the recent Covid-19 pandemic, protein-cage-based scaffolds played a pivotal role in vaccine development. Beyond vaccines, these protein cages have proven valuable in diverse drug delivery applications thanks to their distinctive architecture and structural stability. Among the various types of protein cages, ferritin-based cages have taken the lead in drug delivery applications. This is primarily attributed to their ease of production, exceptional thermal stability, and nontoxic nature. While ferritin-based cages are commonly employed in anticancer drug delivery and contrast agent delivery, their efficacy in malarial drug delivery had not been explored until this study. In this investigation, several antimalarial drugs were encapsulated within horse spleen ferritin, and the binding and loading processes were validated through both experimental and computational techniques. The data unequivocally demonstrate the facile incorporation of antimalarial drugs into ferritin without disrupting its three-dimensional structure. Computational docking and molecular dynamics simulations were employed to pinpoint the precise location of the drug binding site within ferritin. Subsequent efficacy testing on <i>Plasmodium</i> revealed that the developed nanoconjugate, comprising the drug–ferritin conjugate, exhibited significant effectiveness in eradicating the parasite. 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Antimalarial Delivery with a Ferritin-Based Protein Cage: A Step toward Developing Smart Therapeutics against Malaria
Over the past two decades, the utilization of protein cages has witnessed exponential growth driven by their extensive applications in biotechnology and therapeutics. In the context of the recent Covid-19 pandemic, protein-cage-based scaffolds played a pivotal role in vaccine development. Beyond vaccines, these protein cages have proven valuable in diverse drug delivery applications thanks to their distinctive architecture and structural stability. Among the various types of protein cages, ferritin-based cages have taken the lead in drug delivery applications. This is primarily attributed to their ease of production, exceptional thermal stability, and nontoxic nature. While ferritin-based cages are commonly employed in anticancer drug delivery and contrast agent delivery, their efficacy in malarial drug delivery had not been explored until this study. In this investigation, several antimalarial drugs were encapsulated within horse spleen ferritin, and the binding and loading processes were validated through both experimental and computational techniques. The data unequivocally demonstrate the facile incorporation of antimalarial drugs into ferritin without disrupting its three-dimensional structure. Computational docking and molecular dynamics simulations were employed to pinpoint the precise location of the drug binding site within ferritin. Subsequent efficacy testing on Plasmodium revealed that the developed nanoconjugate, comprising the drug–ferritin conjugate, exhibited significant effectiveness in eradicating the parasite. In conclusion, the findings strongly indicate that ferritin-based carrier systems hold tremendous promise for the future of antimalarial drug delivery, offering high selectivity and limited side effects.
期刊介绍:
Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.