A novel hierarchical targeting and controllable smart nanoparticles for enhanced in situ nuclear photodynamic therapy

Photodynamic therapy(PDT)is a promising and non-invasive treatment for various cancers.Although nuclear PDT has considerable therapeutic prospects,it is still hindered by the non-specific recognition of tumor tissues or the degradation of nuclear targeting cationic groups by enzymes in the blood.Herein,a hierarchical targeted and controlled release strategy is proposed by using folate-modified poly-β-cyclodextrin(poly-β-CD)as a nano-carrier for loading nuclear localization signals(NLSs)-conjugated photosensitizer PAP(PAP=pyropheophorbide a-PAAKRVKLD).Excitingly,the obtained FA-CD@PAP(FA=folic acid)and nanoparticles(NPs)can specifically recognize tumor cells overexpressing folate receptors(FR)to remarkedly enhance the intracellular accumulation.Furthermore,the encapsulated PAP can be released under acidic conditions to realize precise nuclear localization.The reactive oxygen species(ROS)generated by the intranuclear-accumulated PAP upon irradiation can oxidize and destroy DNA chains or DNA repair enzymes instantaneously,which can directly induce cell death.As a result,FA-CD@PAP NPs exhibit excellent tumor regression and negligible side effects.This work provides an intelligent nuclear-targeted delivery strategy for in situ nuclear PDT with extremely prominent efficacy and high biological safety.

3D geological suitability evaluation for underground space based on the AHP-cloud model

Urban development continues to reduce the amount of available ground space.The development of underground space is thus gath-ering increasing attention to alleviate ground congestion.However,there is currently a lack of a three-dimensional(3D)evaluation method to systematically evaluate the geological conditions of underground space and possible geological disaster risks caused by rock and soil masses.This paper presents an engineering geological suitability assessment framework based on 3D geological modeling and an analytic hierarchy process(AHP)-cloud model.As the basis for 3D evaluation,a 3D structural model of the study area is established based on the drilling data and geological profiles.Then the structural model is partitioned to obtain interpolation grids,and the ordinary Kriging interpolation method is applied to attribute interpolation.All the attributes are exported from the geological model,and the rock and soil masses are divided into four categories according to their engineering properties,namely soft soil,sandy soil,cohesive soil,and rock,upon which a targeted hierarchy structure is established based on the attributes that impact the suitability.This paper intro-duces the cloud model to characterize the uncertainty of these evaluation indexes,which synthesizes an AHP method,thus it is referred to as the AHP-cloud model.This new model is used to evaluate the geological suitability of underground space in the Sanlong Bay district,Foshan City,Guangdong,China.In addition,we also determine the excavation difficulty at different depths according to the lithology and weathering degree of the study area.The limitations and future directions of the proposed method are discussed,including the influ-encing factors and weight determination.