While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)...While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models.In addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates.Before the clinical translation of NDX,it is necessary to verify the safety of ND in large mammals.Studies of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical assessment.Herein,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle dogs.The study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection methods.The dogs are monitored for their health phenotype changes in continuous 5 days.Blood and urine obtained are for clinical pathology research.The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model.This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.展开更多
Cells represent the basic units of life and contain an intertwined network of signaling and regulatory circuitries that drive the processes of life.These processes include the mediation of mechano-sensation,onset of a...Cells represent the basic units of life and contain an intertwined network of signaling and regulatory circuitries that drive the processes of life.These processes include the mediation of mechano-sensation,onset of and protection against disease,inflammation,and others.In the network of bio-complex systems,each pathway interacts nonlinearly with others through different molecular intermediates.As a result,specific functionalities can not be simply linked to the cellular molecules in isolation.A complex system generally possesses very rich information content that can be characterized by the following features:(i)they contain a large number of building blocks;(ii)their interactions among building blocks and with their environment;(iii)they display organization without an external organizing principle being applied;and(iv)they exhibit adaptability and robustness.These properties account for the innate intelligence of biology and its ability to regulate its homeostatic behavior.However,this same complexity underlies,in cancer for example,challenges towards disease management,as the addressing of singular pathways with therapeutic compounds is not sufficient.Therefore,combinatorial therapy often serves as a key strategy towards tumor suppression.Because iterative searching for optimized therapeutic combinations is indeed a daunting,if not preclusive task,we introduce the feedback system control(FSC)scheme,which may serve as a clinically relevant approach,provided a translational approach towards drug delivery is employed.Due to their innate biocompatibility,which has been comprehensively observed,as well as their ability to delivery virtually any type of therapeutic in a sustained fashion due to their unique surface properties,nanodiamonds may serve as a foundation for nanoenabled combinatorial therapy.展开更多
基金The work is partially funded by the National Natural Science Foundation of China(No.81871448)the National Key Research and Development Program of China(Nos.2017YFC0107603 and 2017ZX10203205-006-002)the Medical-Engineering Cross Foundation of Shanghai Jiao Tong University(Nos.YG2017QN52,ZH2018QNA54,and ZH2018QNA49).
文摘While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models.In addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates.Before the clinical translation of NDX,it is necessary to verify the safety of ND in large mammals.Studies of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical assessment.Herein,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle dogs.The study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection methods.The dogs are monitored for their health phenotype changes in continuous 5 days.Blood and urine obtained are for clinical pathology research.The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model.This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.
基金supported by the Center for Cell Control(PN2 EY018228)through NIH Roadmap for Nanomedicinethe Center for Scalable and Integrated Nanomanufacturing(SINAM)under National Science Foundation(CMMI-0751621)+3 种基金support from a National Science Foundation CAREER Award(CMMI-0846323)National Science Foundation Mechanics of Materials program grant(CMMI-0856492)V Foundation for Cancer Research V Scholars Award,NSF grant DMI-0327077Wallace H.Coulter Foundation Early Career Award in Translational Research.
文摘Cells represent the basic units of life and contain an intertwined network of signaling and regulatory circuitries that drive the processes of life.These processes include the mediation of mechano-sensation,onset of and protection against disease,inflammation,and others.In the network of bio-complex systems,each pathway interacts nonlinearly with others through different molecular intermediates.As a result,specific functionalities can not be simply linked to the cellular molecules in isolation.A complex system generally possesses very rich information content that can be characterized by the following features:(i)they contain a large number of building blocks;(ii)their interactions among building blocks and with their environment;(iii)they display organization without an external organizing principle being applied;and(iv)they exhibit adaptability and robustness.These properties account for the innate intelligence of biology and its ability to regulate its homeostatic behavior.However,this same complexity underlies,in cancer for example,challenges towards disease management,as the addressing of singular pathways with therapeutic compounds is not sufficient.Therefore,combinatorial therapy often serves as a key strategy towards tumor suppression.Because iterative searching for optimized therapeutic combinations is indeed a daunting,if not preclusive task,we introduce the feedback system control(FSC)scheme,which may serve as a clinically relevant approach,provided a translational approach towards drug delivery is employed.Due to their innate biocompatibility,which has been comprehensively observed,as well as their ability to delivery virtually any type of therapeutic in a sustained fashion due to their unique surface properties,nanodiamonds may serve as a foundation for nanoenabled combinatorial therapy.
