## 4 Conclusions  
The ADCs that are approved or in clinical development for cancer treatment are almost exclusively based on the use of highly cytotoxic payloads. To our knowledge, nucleic acid mimics have never been used as payloads, though they are known to interfere with the function of DNA interacting enzymes and/or modulate the expression of genes involved in cancer cell growth. Our study provides the first experimental evidences that it is possible to conjugate high molecular weight oligoamide-based DNA mimics onto monoclonal antibodies with a controlled drug-antibody ratio, and that the resulting ADC binds to its extracellular target before its internalization into cells. Our results further extend the potential of using the ADC strategy to deliver other categories of payloads that are not necessarily highly cytotoxic but would rather be used to potentiate the action of other drugs that are administered in combination, including conventional chemotherapies.  
**Supplementary Materials:** The following are available online at [[https://www.mdpi.com/article/10.3390/ph14070624/s1](https://www.mdpi.com/article/10.3390/ph14070624/s1)]([https://www.mdpi.com/article/10.3390/ph14070624/s1](https://www.mdpi.com/article/10.3390/ph14070624/s1)), Scheme S1: Solid Phase Synthesis of diphenylthio-Mal-Cap-foldamer 3 (See experimental procedures for details), Figure S1: 1H NMR spectra (400 MHz) in H\({}_{2}\)O/D\({}_{2}\)O 9:1 (vol/vol), 50 mM NH\({}_{4}\)HCO\({}_{3}\) at 298 K before (bottom) and after (top) the coupling reaction with the diphenylthio-maleimido-capric acid linker 2, Figure S2: Analytical RP-HPLC profile of pure diphenylthio-Mal-Cap-foldamer 3, Figure S3: Multicharged species observed by ESI HRMS analysis (anionic mode) of pure dithiophenyl-Mal-Cap-foldamer 3, Figure S4: Internalization of the ADC or trastuzumab in MCF-7 and T-47D cells, Figure S5: MS analysis of ADC TrastuzumabMal-Cap-foldamer 4, Figure S6: Gating for FACS analysis, Table S1: Average drug-to-antibody ratio (DAR) calculation.  
Conceptualization, C.D.-S., I.H., M.D.R., N.J., P.P.; Investigation, A.G., C.D.-S., I.A.M.A., M.D.R., N.J., V.C., V.G., S.L.; Resources, C.D.-S., I.H., N.J.; Visualization, A.G., M.D.R., N.J., V.G.; Validation, A.G., C.G., I.A.M.A., M.D.R., N.J., V.C., V.G.; Writing--original draft preparation, C.D.-S., I.A.M.A., N.J., P.P., V.C.; Writing--review and editing, C.D.-S., C.G., I.A.M.A., I.H., N.J., V.C.; Funding acquisition, C.D.-S., C.G., I.H., N.J., P.P.; Supervision, I.H., N.J., P.P. All authors have read and agreed to the published version of the manuscript.  
This work was funded by the LabEx MabImprove (Grant # ANR-10-LABX-53), the SIRIC Montpellier Cancer (Grant # INCa-DGOS-Insem_12553), the Canceropole GSO-INSERM (Grant # 2019-E04), la Ligue contre le Cancer (comites 18, 35, 37, 41, 44, 53, 72, 79, 85). [PERSON] is a recipient of a fellowship from Region Centre-Val de Loire.  
Not applicable.  
Data Availability Statement: Data is contained within the article and supplementary material.  
We thank [PERSON], [PERSON] and [PERSON] (team IMT, GICC EA7501) for mass analysis. We thank the Hospital Pharmacy of the Tours Teaching Hospital for providing us with clinical grade leftovers of trastuzumab (Roche).  
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.