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.

Neoadjuvant Chemotherapy Based on Abraxane/Human Neutrophils Cytopharmaceuticals with Radiotherapy for Gastric Cancer

“…Currently, for those unresectable cancers, palliative chemotherapy regimens based on tumor progression are clinically preferred for extending patients lifetime,[2b,4] while local radiation behaves as a supplement and contribution to antitumor effect of chemotherapy . Nevertheless, some crucial dilemmas of chemo‐radiotherapy, such as the limited tumor‐targeting of chemotherapeutics and undesired systemic side effects, restrict the antitumor efficacy, thereby driving the development of novel therapeutic strategies.…”

Oligonucleotide Aptamer-Mediated Precision Therapy of Hematological Malignancies

“… 110 Animal model studies demonstrated specific accumulation of Apt-NMed in ALCL tumor sites, induction of higher inhibition of ALCL tumor growth, and improved survival of the treated mice; Apt-NMed did not affect off-target tumors in the same xenograft mouse, thus opening a new avenue for precision therapy of ALCL. 110 …”

“… 109 Furthermore, Zhao et al. 110 developed a multifunctional aptamer-nanomedicine (Apt-NMed) simultaneously achieving targeted chemotherapy and gene therapy of ALCL. Apt-NMed was formulated by the self-assembly of ssDNA aptamer and ALK-specific siRNA followed by self-loading of the chemotherapeutic drug Dox.…”

“…Apt-NMed was formulated by the self-assembly of ssDNA aptamer and ALK-specific siRNA followed by self-loading of the chemotherapeutic drug Dox. 110 Intracellular delivery of Apt-NMed triggered rapid Dox release and intracellular ALK-specific siRNA delivery, resulting in the combined chemotherapeutic and oncogene-silencing effects. 110 Animal model studies demonstrated specific accumulation of Apt-NMed in ALCL tumor sites, induction of higher inhibition of ALCL tumor growth, and improved survival of the treated mice; Apt-NMed did not affect off-target tumors in the same xenograft mouse, thus opening a new avenue for precision therapy of ALCL.…”

Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics

“…For combined chemo‐ and gene therapy, both ssDNA (single‐stranded DNA) and siRNA (small interfering RNA) were crosslinked into nanostructures along with DOX and aptamer CD30 or AS1411 for the targeted therapy in K299 and U937 cells, which highly express CD30, or in HeLa cells . Subsequently, a triangle DNA origami (TO) with MUC1 was loaded by DOX triangle DNA origami, filled with DOX (TOD).…”