Self‐Assembled Aptamer‐Nanomedicine for Targeted Chemotherapy and Gene Therapy

Abstract Chemotherapy is the mainstream treatment of anaplastic large cell lymphoma (ALCL). However, chemotherapy can cause severe adverse effects in patients because it is not ALCL‐specific. In this study, a multifunctional aptamer‐nanomedicine (Apt‐NMed) achieving targeted chemotherapy and gene therapy of ALCL is developed. Apt‐NMed is formulated by self‐assembly of synthetic oligonucleotides containing CD30‐specific aptamer and anaplastic lymphoma kinase (ALK)‐specific siRNA followed by self‐loading of the chemotherapeutic drug doxorubicin (DOX). Apt‐NMed exhibits a well‐defined nanostructure (diameter 59 mm) and stability in human serum. Under aptamer guidance, Apt‐NMed specifically binds and internalizes targeted ALCL cells. Intracellular delivery of Apt‐NMed triggers rapid DOX release for targeted ALCL chemotherapy and intracellular delivery of the ALK‐specific siRNA induced ALK oncogene silencing, resulting in combined therapeutic effects. Animal model studies reveal that upon systemic administration, Apt‐NMed specifically targets and selectively accumulates in ALCL tumor site, but does not react with off‐target tumors in the same xenograft mouse. Importantly, Apt‐NMed not only induces significantly higher inhibition in ALCL tumor growth, but also causes fewer or no side effects in treated mice compared to free DOX. Moreover, Apt‐NMed treatment markedly improves the survival rate of treated mice, opening a new avenue for precision treatment of ALCL.