Enhancing the active tumor targeting ability and decreasing the clearance of reticuloendothelial system(RES)are important issues for drug delivery systems(DDSs)in cancer therapy.In recent years,cell membrane camouflage,as one of the biomimetic modification strategies,has shown huge potential.Many natural properties of source cells can be inherited,allowing the DDSs to successfully avoid phagocytosis by macrophages,prolong circulation time,and achieve homologous targeting to lesion tissue.In this study,a cancer cell membrane camouflaged nanoplatform based on gelatin with a typical core-shell structure was developed for cancer chemotherapy.Doxorubicin(DOX)loaded gelatin nanogel(NG@DOX)acted as the inner core,and 4T1(mouse breast carcinoma cell)membrane was set as the outer shell(M-NG@DOX).The M-NG platform enhanced the ability of homologous targeting due to the surface protein of cell membrane being completely retained,which could promote the cell uptake of homotypic cells,avoid phagocytosis by RAW264.7 macrophages,and therefore increase accumulation in tumor tissue.Meanwhile,due to the better controlled drug release capability of M-NG@DOX,premature release of DOX in circulation could be reduced,minimizing side effects in common chemotherapy.As a result,the biomimetic nanoplatform in this study,obtained by a cancer cell membrane camouflaged drug delivery system,efficiently reached desirable tumor elimination,providing a significant strategy for effective targeted therapy and specific carcinoma therapy.
Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.
The existence of tumor immunosuppressive microenvironment(TIME)is the major determinant for the poor efficacy of current tumor immunotherapy.Tumor-associated macrophages(TAMs)tend to become tumor-promoting M2-like phenotype and hinder immune response in solid tumors.Repolarization of TAMs from M2 to anti-tumor M1 phenotype is robust for remodeling the TIME.Herein,we developed a redox-responsive nanogel as the delivery system of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)prodrug for potent cancer immunotherapy.The nanogel(denoted as R848-Gel)was obtained by emulsion polymerization of HSEMA and R848 prodrug(R848-HSEMA),whose size was appropriate 100 nm.R848-Gel could be internalized by macrophages and dendritic cells in vitro,and effectively repolarized M2 into M1 macrophages and promoted the maturation of antigen-presenting cells.In vivo study indicated that the R848-Gel showed a stronger tumor inhibitory effect and no drastic body weight change compared with free drug.Immune cell analysis after the treatment indicated that R848-Gel was helpful to activating the TIME.In summary,this study provides a simple but effective vehicle for R848 to improve cancer immunotherapy.
Kai-Shuo WangYu-Feng JinQi-Song TongYong-Cong HuangZhen-Lin GaoSui-Juan ZhengJing-Yang ZhangJun WangJin-Zhi Du
