The Research Of Tumor Targeted Therapy With A Co-formulation Composed Of MiR-16 And Adriamycin

Tumor is one of the major diseases threatening the health of human beings.As a typical representative of the anthracycline-based antitumor drugs,doxorubicin(DOX)has broad spectrum antitumor activity.However,DOX has a strong side-effect because of its non-specific distribution.It can accumulate widely in the normal tissue,such as the heart,liver and kidney which may lead to congestive heart failure even death.Therefore,we need to find strategies to reduce the toxicity of doxorubicin.In theory,it can be realized via the targeted delivery of DOX or increasing the DOX sensitivity of cancer cells to reduce the therapeutic dose of DOX,We developed a co-formulation composed of a cell proliferation suppressive microRNA-miR-16 and DOX based on the characteristic of DOX can be inserted into the double-stranded miR-16.Polyethylenimine(PEI)combined DOX/miR-16 intercalation tightly to form compact complex which then combined with HSA to form HMD,a stable nanoparticles.Then we found HMD could be transported into cells by gp60(the main receptor of HSA)mediated endocytosis.PEI can targeted deliver DOX and miR-16 to tumor tissue effectively and decrease the distribution in normal tissues,which significantly reduced the side effects of DOX.In the orthotopic hepatic Heps tumor model,HMD exhibited an obvious enhanced anticancer effect compared to free DOX.The innovation of this paper is the co-formulation composed of tumorsuppressive miR-16 and DOX,which increased the sensitivity of tumor to DOX.Also,miR-16 and DOX were innovatively developed as a tumor-targeting nano pharmaceutical formulation,improving the distribution of DOX in the tumor cells,reducing the non-specific distribution and the side effects of DOX.The final DOX/miR-16 nano formulation performs a strong inhibition of tumor effects and low physiological toxicity,and has a promising application prospect.