Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanopa...Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.展开更多
The emergence of nanoparticles(NPs)has attracted tremendous interest of the scientific community for decades due to their unique properties and potential applications in diverse areas,including drug delivery and thera...The emergence of nanoparticles(NPs)has attracted tremendous interest of the scientific community for decades due to their unique properties and potential applications in diverse areas,including drug delivery and therapy.Many novel NPs have been synthesized and used to reduce drug toxicity,improve bio-availability,prolong circulation time,control drug release,and actively target to desired cells or tissues.However,clinical translation of NPs with the goal of treating particularly challenging diseases,such as cancer,will require a thorough understanding of how the NP properties influence their fate in biological systems,especially in vivo.Many efforts have been paid to studying the interactions and mechanisms of NPs and cells.Unless deliberately designed,the NPs in contact with biological fluids are rapidly covered by a selected group of biomolecules especially proteins to form a corona that interacts with biological systems.In this view,the recent development of NPs in drug delivery and the interactions of NPs with cells and proteins are summarized.By understanding the protein-NP interactions,some guidelines for safety design of NPs,challenges and future perspectives are discussed.展开更多
Owing to the importance of drug delivery in cancer or other diseases' therapy, the targeted drug delivery (TDD) system has been attracting enormous interest. Herein, we model the TDD system and design a novel rod-...Owing to the importance of drug delivery in cancer or other diseases' therapy, the targeted drug delivery (TDD) system has been attracting enormous interest. Herein, we model the TDD system and design a novel rod-like nanocarrier by using the coarse grained model-based density functional theory, which combines a modified fundamental measure theory for the excluded-volume effects, Wertheim's first-order thermodynamics perturbation theory for the chain connectivity and the mean field approximation for van der Waals attraction. For comparison, the monomer nanocarrier TDD system and the no nanocarrier one are also investigated. The results indicate that the drug delivery capacity of rod-like nanocarriers is about 62 times that of the no nanocarrier one, and about 6 times that of the monomer nanocarriers. The reason is that the rod-like nanocarriers would self-assemble into the smectic phase perpendicular to the membrane surface. It is the self-assembly of the rod-like nanocarriers that yields the driving force for the targeted delivery of drugs inside the cell membrane. By contrast, the conventional monomer nanocarrier drug delivery system lacks the driving force to deliver the drugs into the cell membrane. In short, the novel rod-like nanocarrier TDD system may improve the drug delivery efficiency. Although the model in this work is simple, it is expected that the system may provide a new perspective for cancer targeted therapy.展开更多
There has been unprecedented progress in the development of biomedical nanotechnology and nanoma- terials over the past few decades, and nanoparticle-based drug delivery systems （DDSs） have great potential for clin-...There has been unprecedented progress in the development of biomedical nanotechnology and nanoma- terials over the past few decades, and nanoparticle-based drug delivery systems （DDSs） have great potential for clin- ical applications. Among these, magnetic drug delivery systems （MDDSs） based on magnetic nanoparticles （MNPs） are attracting increasing attention owing to their favor- able biocompatibility and excellent multifunctional loading capability. MDDSs primarily have a solid core of super paramagnetic maghemite （y-Fe^03） or magnetite （Fe304） nanoparticles ranging in size from 10 to 100nm. Their surface can be functionalized by organic and/or inorganic modification. Further conjugation with targeting ligands, drug loading, and MNP assembly can provide complex magnetic delivery systems with improved targeting efficacy and reduced toxicity. Owing to their sensitive response to external magnetic fields, MNPs and their assemblies have been developed as novel smart delivery systems. In this review, we first summarize the basic physicochemical and magnetic properties of desirable MDDSs that fulfill the requirements for specific clinical applications. Secondly, we discuss the surface modifications and functionalization issues that arise when designing elaborate MDDSs for future clinical uses. Finally, we highlight recent progress in the design and fabrication of MNPs, magnetic assemblies, and magnetic microbnbbles and liposomes as MDDSs for cancer diagnosis and therapy. Recently, researchers have focused on enhanced targeting efficacy and theranostics by applying step-by-step sequential treatment, and by magnetically mod- ulating dosing regimens, which are the current challenges for clinical applications.展开更多
基金the National Natural Science Foundation of China(Grant No.30970785,81273454)Beijing Natural Science Foundation(Grant No.7132113)+2 种基金National Basic Research Program(Grant No.2009CB930303,2013CB932501)Doctoral Foundation of the Ministry of Education(Grant No.20100001110056)Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.
基金financially supported by the National Natural Science Foundation of China(51120135001)the National Basic Research Program of China(2011CB606203)+1 种基金Ph.D.Programs Foundation of Ministry of Education of China(20110101130005)Open Project of State Key Laboratory of Supramolecular Structure and Materials(sklssm201303)
文摘The emergence of nanoparticles(NPs)has attracted tremendous interest of the scientific community for decades due to their unique properties and potential applications in diverse areas,including drug delivery and therapy.Many novel NPs have been synthesized and used to reduce drug toxicity,improve bio-availability,prolong circulation time,control drug release,and actively target to desired cells or tissues.However,clinical translation of NPs with the goal of treating particularly challenging diseases,such as cancer,will require a thorough understanding of how the NP properties influence their fate in biological systems,especially in vivo.Many efforts have been paid to studying the interactions and mechanisms of NPs and cells.Unless deliberately designed,the NPs in contact with biological fluids are rapidly covered by a selected group of biomolecules especially proteins to form a corona that interacts with biological systems.In this view,the recent development of NPs in drug delivery and the interactions of NPs with cells and proteins are summarized.By understanding the protein-NP interactions,some guidelines for safety design of NPs,challenges and future perspectives are discussed.
基金supported by the National Natural Science Foundation of China (20874005, 20736002, 20821004)the National Basic Research Program of China (2011CB706900)+1 种基金Huo Yingdong Fundamental Research Foundation (121070)Novel Team (IRT0807) from Ministry of Education and the Chemical Grid Project of BUCT
文摘Owing to the importance of drug delivery in cancer or other diseases' therapy, the targeted drug delivery (TDD) system has been attracting enormous interest. Herein, we model the TDD system and design a novel rod-like nanocarrier by using the coarse grained model-based density functional theory, which combines a modified fundamental measure theory for the excluded-volume effects, Wertheim's first-order thermodynamics perturbation theory for the chain connectivity and the mean field approximation for van der Waals attraction. For comparison, the monomer nanocarrier TDD system and the no nanocarrier one are also investigated. The results indicate that the drug delivery capacity of rod-like nanocarriers is about 62 times that of the no nanocarrier one, and about 6 times that of the monomer nanocarriers. The reason is that the rod-like nanocarriers would self-assemble into the smectic phase perpendicular to the membrane surface. It is the self-assembly of the rod-like nanocarriers that yields the driving force for the targeted delivery of drugs inside the cell membrane. By contrast, the conventional monomer nanocarrier drug delivery system lacks the driving force to deliver the drugs into the cell membrane. In short, the novel rod-like nanocarrier TDD system may improve the drug delivery efficiency. Although the model in this work is simple, it is expected that the system may provide a new perspective for cancer targeted therapy.
基金financially funded by the National Natural Science Foundation of China (NSFC, 31370019, 61420106012)the project of National Key Basic Research Program of China (2013CB733804)+1 种基金The funding partially comes from the Fundamental Research Funds for the Central Universities (2242016K41072)Zhong Ying Young Scholar of Southeast University as well as the support fromthe Collaborative Innovation Center of Suzhou Nano Science and Technology
文摘There has been unprecedented progress in the development of biomedical nanotechnology and nanoma- terials over the past few decades, and nanoparticle-based drug delivery systems （DDSs） have great potential for clin- ical applications. Among these, magnetic drug delivery systems （MDDSs） based on magnetic nanoparticles （MNPs） are attracting increasing attention owing to their favor- able biocompatibility and excellent multifunctional loading capability. MDDSs primarily have a solid core of super paramagnetic maghemite （y-Fe^03） or magnetite （Fe304） nanoparticles ranging in size from 10 to 100nm. Their surface can be functionalized by organic and/or inorganic modification. Further conjugation with targeting ligands, drug loading, and MNP assembly can provide complex magnetic delivery systems with improved targeting efficacy and reduced toxicity. Owing to their sensitive response to external magnetic fields, MNPs and their assemblies have been developed as novel smart delivery systems. In this review, we first summarize the basic physicochemical and magnetic properties of desirable MDDSs that fulfill the requirements for specific clinical applications. Secondly, we discuss the surface modifications and functionalization issues that arise when designing elaborate MDDSs for future clinical uses. Finally, we highlight recent progress in the design and fabrication of MNPs, magnetic assemblies, and magnetic microbnbbles and liposomes as MDDSs for cancer diagnosis and therapy. Recently, researchers have focused on enhanced targeting efficacy and theranostics by applying step-by-step sequential treatment, and by magnetically mod- ulating dosing regimens, which are the current challenges for clinical applications.
