In order to enhance the targeted delivery of anticancer drugs by polymeric micelles, folic acid(FA), the ligand of folate receptor(FR) over-expressed in the most cancer cells, modified p H-sensitive polymeric micelles...In order to enhance the targeted delivery of anticancer drugs by polymeric micelles, folic acid(FA), the ligand of folate receptor(FR) over-expressed in the most cancer cells, modified p H-sensitive polymeric micelles were designed and fabricated to encapsulate doxorubicin(DOX) by combination of p H-sensitive amphiphilic polymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) with FA-conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide). The prepared micelles were characterized to have about 36 nm in diameter with narrow distribution, well-defined spherical shape observed under TEM and p H-responsive drug release behavior. Moreover, the tumor targeting ability of the FA-modified p H-sensitive polymeric micelles was demonstrated by the cellular uptake, in vitro cytotoxicity to FR-positive KB cells and in vivo real time near-infrared fluorescence imaging in KB tumor-bearing nude mice. The efficient drug delivery by the micelles was ascribed to the synergistic effects of FR-mediated targeting and p H-triggered drug release. In conclusion, the designed FR-targeted p H-sensitive polymeric micelles might be of great potential in tumor targeted delivery of water-insoluble anticancer drugs.展开更多
Over the past two decades,proteolysis-targeting chimeras(PROTACs)have gradually evolved from chemical biology tools into potential clinical candidates,marking a significant advancement in our ability to modulate prote...Over the past two decades,proteolysis-targeting chimeras(PROTACs)have gradually evolved from chemical biology tools into potential clinical candidates,marking a significant advancement in our ability to modulate protein homeostasis for therapeutic purposes1.Unlike conventional targeted therapies,which primarily utilize a target occupancy-driven approach,protein homeostasis modulation strategies intervene through event-driven mechanisms,demonstrating distinct clinical poten tial for undruggable or mutation-prone targets compared to traditional small molecule drugs2.展开更多
Despite the exceptional progress in breast cancer pathogenesis,prognosis,diagnosis,and treatment strategies,it remains a prominent cause of female mortality worldwide.Additionally,although chemotherapies are effective...Despite the exceptional progress in breast cancer pathogenesis,prognosis,diagnosis,and treatment strategies,it remains a prominent cause of female mortality worldwide.Additionally,although chemotherapies are effective,they are associated with critical limitations,most notably their lack of specificity resulting in systemic toxicity and the eventual development of multi-drug resistance(MDR)cancer cells.Liposomes have proven to be an invaluable drug delivery system but of the multitudes of liposomal systems developed every year only a few have been approved for clinical use,none of which employ active targeting.In this review,we summarize the most recent strategies in development for actively targeted liposomal drug delivery systems for surface,transmembrane and internal cell receptors,enzymes,direct cell targeting and dual-targeting of breast cancer and breast cancer-associated cells,e.g.,cancer stem cells,cells associated with the tumor microenvironment,etc.展开更多
基金National Natural Science Foundation of China(Grant No.81673366)。
文摘In order to enhance the targeted delivery of anticancer drugs by polymeric micelles, folic acid(FA), the ligand of folate receptor(FR) over-expressed in the most cancer cells, modified p H-sensitive polymeric micelles were designed and fabricated to encapsulate doxorubicin(DOX) by combination of p H-sensitive amphiphilic polymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) with FA-conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide). The prepared micelles were characterized to have about 36 nm in diameter with narrow distribution, well-defined spherical shape observed under TEM and p H-responsive drug release behavior. Moreover, the tumor targeting ability of the FA-modified p H-sensitive polymeric micelles was demonstrated by the cellular uptake, in vitro cytotoxicity to FR-positive KB cells and in vivo real time near-infrared fluorescence imaging in KB tumor-bearing nude mice. The efficient drug delivery by the micelles was ascribed to the synergistic effects of FR-mediated targeting and p H-triggered drug release. In conclusion, the designed FR-targeted p H-sensitive polymeric micelles might be of great potential in tumor targeted delivery of water-insoluble anticancer drugs.
文摘Over the past two decades,proteolysis-targeting chimeras(PROTACs)have gradually evolved from chemical biology tools into potential clinical candidates,marking a significant advancement in our ability to modulate protein homeostasis for therapeutic purposes1.Unlike conventional targeted therapies,which primarily utilize a target occupancy-driven approach,protein homeostasis modulation strategies intervene through event-driven mechanisms,demonstrating distinct clinical poten tial for undruggable or mutation-prone targets compared to traditional small molecule drugs2.
文摘Despite the exceptional progress in breast cancer pathogenesis,prognosis,diagnosis,and treatment strategies,it remains a prominent cause of female mortality worldwide.Additionally,although chemotherapies are effective,they are associated with critical limitations,most notably their lack of specificity resulting in systemic toxicity and the eventual development of multi-drug resistance(MDR)cancer cells.Liposomes have proven to be an invaluable drug delivery system but of the multitudes of liposomal systems developed every year only a few have been approved for clinical use,none of which employ active targeting.In this review,we summarize the most recent strategies in development for actively targeted liposomal drug delivery systems for surface,transmembrane and internal cell receptors,enzymes,direct cell targeting and dual-targeting of breast cancer and breast cancer-associated cells,e.g.,cancer stem cells,cells associated with the tumor microenvironment,etc.
