摘要
Targeted drug delivery has been widely explored for efficient tumor therapy with desired efficacy but minimized side effects. It is widely known that large numbers of DNA-toxins, such as doxorubicin, genes, reactive oxygen species, serving as therapeutic agents, can result in maximized therapeutic effects via the interaction directly with DNA helix. So after cellular uptake, these agents should be further delivered into cell nuclei to play their essential roles in damaging the DNA helix in cancer ceils. Here, we demonstrate the first paradigm estabJished in our laboratory in developing nucle- ar-targeted drug delivery systems （DDSs） based on MSNs for enhanced therapeutic efficiency in the hope of speeding their translation into the ctinics. Firstly, nuclear-targeting DDSs based on MSNs, capable of intranuclear accumulation and drug release therein, were designed and constructed for the first time, resulting in much enhanced anticancer effects both in vitro and in vivo. Such an MSNs-based and nuclear-targeted drug/agent delivery strategy was further applied to overcome multidrug resistance （MDR） of malignant tumors, intra-nuclearly deliver therapeutic genes, photosensitizers, radio-enhancement agents and photothermal agents to realize efficient gene therapy, photodynamic therapy, radiation therapy and photothermal therapy, respectively.
Targeted drug delivery has been widely explored for efficient tumor therapy with desired efficacy but minimized side effects. It is widely known that large numbers of DNA-toxins, such as doxorubicin, genes, reactive oxygen species, serving as therapeutic agents, can result in maximized therapeutic effects via the interaction directly with DNA helix. So after cellular uptake, these agents should be further delivered into cell nuclei to play their essential roles in damaging the DNA helix in cancer ceils. Here, we demonstrate the first paradigm estabJished in our laboratory in developing nucle- ar-targeted drug delivery systems （DDSs） based on MSNs for enhanced therapeutic efficiency in the hope of speeding their translation into the ctinics. Firstly, nuclear-targeting DDSs based on MSNs, capable of intranuclear accumulation and drug release therein, were designed and constructed for the first time, resulting in much enhanced anticancer effects both in vitro and in vivo. Such an MSNs-based and nuclear-targeted drug/agent delivery strategy was further applied to overcome multidrug resistance （MDR） of malignant tumors, intra-nuclearly deliver therapeutic genes, photosensitizers, radio-enhancement agents and photothermal agents to realize efficient gene therapy, photodynamic therapy, radiation therapy and photothermal therapy, respectively.
基金
This work was financially supported by National Natural Science Foundation of China （Grant No. 51402338） and Youth Innovation Promotion Association CAS （Grant No. 2017299）.
