Multifunctional Microvesicles Based Drug Delivery Systems:from Construction To Their Applications Towards Tumor Therapy

Since 21st century,cancer has become one of the most fatal diseases that greatly influenced the health of human beings.Attributed to the modern advanced synthesis systems and abundant approaches for characterizing the nanomaterials,kinds of nanomaterials based drug delivery systems(DDS)have been gradually developed and applied towards tumor diagnosis and therapy.Except for their positive influences,conventional nanomaterial for constructing DDS intrinsically contained some flaws including complicated synthesis procedures,complex surface functionalization processes together with potential cytotoxicity.Therefore,developing a king of DDS consisted of multifunction,excellent biocompatibility et al has been one of the challenges among the anti-tumor fields.In recent years,cell derived microvesicles has successfully explored as a new kind of DDS for tumor diagnosis and therapy due to its unique characteristics such as preferable compatibility and good stability within the physiological environment.In this text,based on the appealing characteristics of cell derived microvesicles(preferable compatibility and ease to modificated et al),we fulfilled to cure breast cancer and cervical cancer with the aid of the constructed multifunctional DDS through phospholipid derivative substitution strategy.The detailed work is depicted as follow.(1)On the basis of phospholipid derivative substitution technology developed in our previous researches,in the meantime,in combination with the formation mechanism of cell derived microvesicles.We successfully modified the membrane with multifunction.Firstly,1%DSPE-PEG-Biotin and 1%DSPE-PEG-Folate were added into the culture medium.Based on the principle of the dynamic substitution processes occurred between the maternal cell membrane and phospholipid with in the culture medium,we successfully achieved to modify the cell membrane with both biotin and folate during the cell cultivation course.During this process,the membrane of cell derived microvesicles was naturally modified with both biotin and folate.MVs simultaneously modified with both biotin and folate was successfully collected through super centrifugation and purification.(2)DOX and ICG were packaged into MVs through electroporation technique.Results revealed that both the temperature and the concentration of drugs with the supernatant increased accompanied with the increased 808 nm laser irradiation periods.In the meantime,TEM consequences also confirmed that the membrane structure of MVs began to crack,even destroy with the increased irradiation periods.The constructed DDS was used for the therapy of cervical cells,consequence proved that cell viability dropped apparently as the increased irradiation periods.Different formats of DDS were used to incubate with cells,results further disclosed that ICG could effectively adjusted the release of anti-tumor drug,also acted together with DOX for the synergistic anti-tumor activities.Therefore,we constructed a NIR induced drug release DDS for the synergistic photothermal and chemotherapy towards cervical cells.(3)Firstly,based on the phospholipid substitution technique,we achieved to modify the membrane of MVs with both folate and biotin.Secondly,paclitaxel and Bcl-2 siRNA were simultaneously packaged into the cavity of MVs.Finally,the multifunctional MVs was applied for the therapy towards both in vitro/vivo.In vitro results revealed that the constructed DDS displayed excellent anti-tumor efficacy.In vivo consequences further proved that the constructed DDS not only possessed real-time imaging capability,also displayed high tumor targeting ability,in the meantime,it shown excellent anti-tumor capability.In summary,we successfully constructed a DDS equipped with real-time imaging,enhanced tumor targeting ability as well as synergistic anti-tumor capability.