Aptamer-Peptide Conjugates as Targeted Chemosensitizers for Breast Cancer Treatment.

High levels of heat shock protein 70 (HSP70) in tumors are commonly associated with poor prognosis, enhanced doxorubicin (DOX)-induced cardiotoxicity, and even drug resistance in DOX-related cancer chemotherapy. Several peptides possess remarkable protein inhibition and chemosensitization effects, which are attributed to their specific targeting ability against HSP70. However, the inherent poor cell penetration capacity considerably restricts the biomedical applications of these peptides. We herein describe the design and development of anti-MUC1 aptamer-peptide conjugates (ApPCs) as targeted chemosensitizers to overcome the above-mentioned issues. Moreover, DOX could be loaded on the ApPC to deliver the DOX-enclosed agent ApPC-DOX, which simultaneously acts as a targeted chemosensitizer and anticancer agent for combating drug resistance in breast cancer therapy. This innovative, engineered biocompatible conjugate not only enhances the sensitivity of DOX-resistant cells but also alleviates cardiotoxicity of DOX in vivo, highlighting the success of this targeted chemosensitizer strategy.

Aptamer Enables Consistent Maytansine Delivery through Maintaining Receptor Homeostasis for HER2 Targeted Cancer Therapy.

Although the extensive clinical use of the ADC trastuzumab-DM1(T-DM1) for human epidermal growth factor receptor 2 (HER2) targeted cancer therapy, many patients who initially respond to T-DM1 treatment eventually met the insufficient efficacy issue, which is partly attributed to the decreased amount of surface HER2 caused by HER2 degradation in target cells. In our study, we have engineered a HER2 targeted DNA aptamer-DM1 conjugate (HApDC) that can maintain the homeostasis of surface HER2 on the target cancer cell. These conclusions are supported by determining the efficient internalization of HApDC into HER2 overexpressed BT474 and SKBR3 cancer cell lines and by identifying the membranal HER2 level on HApDC-treated BT474 cells. Consistent with the impressive in vitro properties of our newly developed anticancer agent, DM1 could precisely be delivered to the tumor tissue in BT474 xenografted mouse models, because of the specific recognition of aptamer. Noteworthy, HApDC exhibited excellent in vivo tumor inhibition function with much lower healthy organ toxicity, compared with the free drug, which might be explained by the persistently targeted DM1 delivery, which is attributed to the remaining HER2 levels on cells.

Hierarchical Fabrication of DNA Wireframe Nanoarchitectures for Efficient Cancer Imaging and Targeted Therapy.

Though small-molecule drugs play a crucial role in cancer treatment, intrinsic issues such as poor solubility and systematic toxicity have considerably mitigated their anticancer functions and caused unwanted side effects. To achieve satisfying therapeutic efficiency, it is essential to develop innovative targeting systems for precise and efficient delivery of anticancer drugs. In this work, a hierarchical self-assembly strategy was applied to fabricate a core-shell nanoarchitecture composed of a DNA octahedral wireframe and chemodrug-functionalized Sgc8c aptamer. The integrated enhanced permeability and retention effect of the DNA nanostructure and active targeting ability of the Sgc8c aptamer allowed the highly selective chemodrug delivery and in vivo efficient imaging and treatment. The advantage of our multifunctional nanostructure was further highlighted by its impressive serum stability, excellent accumulation ability, deep penetration capability, significantly improved therapeutic efficacy, and favorable biosafety. This study showed promising potential of such a core-shell DNA nanoarchitecture in precise drug loading control, drug delivery, and personal medicine.