Nanoparticulate drug delivery systems(Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such...Nanoparticulate drug delivery systems(Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity.Recently, pure drug nano-assemblies(PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.展开更多
Assembly sequence planning will be more difficult due to the increasingcomplexity of products. An integrated approach to assembly sequence planning of complex productsapplying de-composition-planning-combination strat...Assembly sequence planning will be more difficult due to the increasingcomplexity of products. An integrated approach to assembly sequence planning of complex productsapplying de-composition-planning-combination strategy is presented. First, an assembly is decomposedinto a hierarchical structure using an assembly structure representation based on connectors. Then,an assembly planning system is used to generate the sequences that are locally optimal for eachleaf partition hi the structure hierarchy. By combining the local sequences systematically in abottom-up manner and choosing suitable ones from the merged sequences, the assembly sequence of eachparent structure including the whole assembly is generated. An integrated system has beencompleted. A complex product is given to illustrate the feasibility and the practicality of theapproach.展开更多
Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constru...Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib(Gefi),ferrocene(Fc)and dihydroartemisinin(DHA)for the combined therapy of both ferroptosis and apoptosis.In the tumor microenvironment,this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH.Interestingly,the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc,further executing tumor cell death with concomitant chemotherapy by Gefi.More importantly,this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis,as well as no noticeable side-effects during treatments.This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.展开更多
Nanomedicines have shown great promise in cancer therapy,but are challenged by limited drug loading,safety concerns of drug carriers,and complexity of function integration.Recently,carrier-free nanomedicines produced ...Nanomedicines have shown great promise in cancer therapy,but are challenged by limited drug loading,safety concerns of drug carriers,and complexity of function integration.Recently,carrier-free nanomedicines produced by supramolecular assembly of small-molecule therapeutic functionalities and their conjugates were proposed to address these issues.These nanomedicines achieve very high drug loading,enhanced tumor accumulation and improved therapeutic efficiency,and avoid carrier-related safety problems.In this review article,the applications of these nanomedicines in chemotherapy,photodynamic therapy,photothermal therapy as well as combination therapies will be reviewed.The concept of nanomedicine design and mechanism of supramolecular assembly will be discussed.Finally,future perspectives of carrier-free supramolecular nanomedicines for cancer therapy will be highlighted.展开更多
基金supported by Liaoning Science&Technology project(2019-ZD-0465,China)。
文摘Nanoparticulate drug delivery systems(Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity.Recently, pure drug nano-assemblies(PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.
基金This project is supported by National Natural Science Foundation of China (No.59990470-2).
文摘Assembly sequence planning will be more difficult due to the increasingcomplexity of products. An integrated approach to assembly sequence planning of complex productsapplying de-composition-planning-combination strategy is presented. First, an assembly is decomposedinto a hierarchical structure using an assembly structure representation based on connectors. Then,an assembly planning system is used to generate the sequences that are locally optimal for eachleaf partition hi the structure hierarchy. By combining the local sequences systematically in abottom-up manner and choosing suitable ones from the merged sequences, the assembly sequence of eachparent structure including the whole assembly is generated. An integrated system has beencompleted. A complex product is given to illustrate the feasibility and the practicality of theapproach.
基金financial supports from National Natural Science Foundation of China(32000992,21977081,32101124)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR23C100001)+1 种基金Wenzhou Medical University(KYYW201901)Zhejiang Qianjiang Talent Plan(QJD20020224)
文摘Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib(Gefi),ferrocene(Fc)and dihydroartemisinin(DHA)for the combined therapy of both ferroptosis and apoptosis.In the tumor microenvironment,this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH.Interestingly,the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc,further executing tumor cell death with concomitant chemotherapy by Gefi.More importantly,this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis,as well as no noticeable side-effects during treatments.This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.
基金supported by the Basic Research Program of Science and Technology Commission of Shanghai Municipality(No.21JC1401800)。
文摘Nanomedicines have shown great promise in cancer therapy,but are challenged by limited drug loading,safety concerns of drug carriers,and complexity of function integration.Recently,carrier-free nanomedicines produced by supramolecular assembly of small-molecule therapeutic functionalities and their conjugates were proposed to address these issues.These nanomedicines achieve very high drug loading,enhanced tumor accumulation and improved therapeutic efficiency,and avoid carrier-related safety problems.In this review article,the applications of these nanomedicines in chemotherapy,photodynamic therapy,photothermal therapy as well as combination therapies will be reviewed.The concept of nanomedicine design and mechanism of supramolecular assembly will be discussed.Finally,future perspectives of carrier-free supramolecular nanomedicines for cancer therapy will be highlighted.
