Oligonucleotide aptamers are a class of molecular ligands with high affinity and specificity for a wide range of biological targets. As “chemical antibodies”, aptamers can be rapidly synthesized and easily conjugated to various functional agents for clinical use. Anaplastic large cell lymphoma (ALCL) is the most common T-cell lymphoma in children. ALCL cells are characterized by abnormal expression of surface CD30 and the Anaplastic Lymphoma Kinase (ALK) oncogene, a key pathogenic factor for lymphoma development. CHOP chemotherapy is the current treatment for ALCL, however, it can cause serious side effects. To dress clinical needs, we developed an aptamer-nanomedicine (Apt-NM) through self-assembly of functional oligonucleotides and self-loading of chemotherapeutic drugs. The formed Apt-NM contained CD30 aptamer sequences for cell targeting, siRNA sequence for ALK oncogene silencing, and drug payload for chemotherapy. DSL assay showed that the Apt-NM had a peak size of 58 nm and was stable in PBS. Atomic force microscopy and scanning electron microscopy reviewed uniform shape and size of the Apt-NM. Cell binding analysis demonstrated that Apt-NM specifically targeted ALCL cells, but did not react to CD30(-) cells. Confocal microscopy confirmed that specific cell binding resulted in rapid intracellular delivery of Apt-NM into lysosomes via endocytosis for drug release, and cytoplasm through macropinocytosis to enable siRNA-induced gene silencing. In vitro studies indicated that Apt-NM treatment caused growth inhibition of ALCL cells through combined chemotherapy and gene therapy effects. In vivo studies showed that systemic administration of Apt-NM selectively targeted ALCL tumor, but not seen in CD30(-) tumor site in the same xenograft mouse. Furthermore, Apt-NM treatment showed markedly higher inhibition in xenograft ALCL tumor growth than free drug treatment. Importantly, Apt-NM treatment significantly improved the survival rate and also induced tumor-free status of treated mice.

Self-assembled aptamer-nanomedicine for both target chemotherapy and gene therapy

254th National Meeting (2017)

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