Regulating The Biological Effects Of Flexible Mesoporous Organosilicate Nanoparticles For Efficient Photodynamic Antitumor

Flexibility,as an important mechanical property of nanoparticles,plays an important role in regulating many biological processes.Such as blood circulation,tumor tissue penetration,cell internalization and metabolism.It has been reported that nanoparticles with low flexibility can overcome physiological obstacles（extracellular matrix,cell membrane）to realize longer circulation time during blood circulation.Simultaneously,flexible nanoparticles can change its morphology during interacting with the cell,which greatly reduce the deformation degree and energy of cell membrane in the process of internalization,resulting in enhancing the cellular uptake of flexible nanoparticles.In addition,as it permeates in the tumor tissue,flexible nanoparticles can"squeeze"through the narrow cell gap and reach the deep tissue,leading to deep drug delivery.Combining with the advantages of flexible mesoporous organosilica nanoparticles（MONs）,we cleverly synthesized five MONs with different degree of flexible framework and explored their effects in vitro cell uptake,in vivo circulation time and distribution.Then,MONs with flexible framework are loaded with photosensitizer to achieve prolong their blood circulation,increase the rate of tumor accumulation,reduceeside effects and enhance antitumor efficacy.Centered on the above points,this paper mainly carried out the following two aspects of work:（1）Five kinds of flexible hollow nanocapsules(MONS₀-HA,MONS₂₀-HA,MONS₅₀-HA,MONS₁₀₀-HA,MONS₂₀₀-HA)with uniform size,good dispersibility and different degree of flexible framework were synthesized by dispersing hyaluronic acid modified MONs（MONS-HA）in different concentrations of sodium hydroxide solution（0,20,50,100,200 m M）.And their biological effects were also studied at both cell and in vivo levels.It found that the blood circulation time,tumor enrichment and tumor cell uptake were gradually enhanced with the increasing flexibility of the MONs_0-100-HA.However,as the flexibility keep going up(MONS₂₀₀-HA),the cell uptake,cycle time and tumor enrichment of the nanocapsules began to reduce.（2）Soft MONs（SMONs）were prepared by alkali priority etching method.Then hyaluronic acid,photosensitizer Ce6 and mitochondrial molecular carboxylic triphenylphosphine（CTPP）were covalently modified on SMONs’surface（SMONs-CTPP-Ce6）.The prepared SMONs-CTPP-Ce6possessed good dispersibility,uniform size and mitochondrial targeting function.Compared to the traditional MONs photodynamic nanoplatform（MONs-CTPP-Ce6）,the SMONs-CTPP-Ce6 had better cell uptake,mitochondrial co-localization and anti-tumor effect.