**4. Conclusions**

In this study, tumor-homing pH-sensitive EV blends were fabricated using tumor-specific EVs (extracted from SK-N-MC and BT-474 tumor cells) and pH-sensitive HDEA. HDEA and DOX were incorporated in two different EVs through sonication; subsequently, they were blended in a weight ratio of 50:50. The EV blends, comprising two different EVs, can target two different parent tumor cells owing to the EVs' homing ability. In addition, the pH-sensitive disruption of EVs owing to DEAP molecules promoted DOX release. Consequently, the EV blends killed the heterogeneous parent tumor cells effectively. Hence, we believe that EV blends with tumor cell targeting ability, the rapid release of DOX at the endosomal pH, and the enhanced antitumor effect may be novel strategies for treating various tumors.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1999-4923/12/4/372/s1, Figure S1. 1H-NMR analysis of HDEA. Figure S2. <sup>1</sup>H-NMR analysis of HDOC. Figure S3. TEM analysis of intact (a) BTEV or SKEV. (b) Western blot analysis of the TSG 101 (tumor susceptibility gene 101), ER-α (estrogen receptor alpha), or Tau (tau protein) in BTEVs or SKEVs.

**Author Contributions:** Conceptualization, E.S.L., Y.S.Y., and K.T.O.; methodology, J.P. and H.L.; investigation, J.P. and H.L.; data curation, J.P. and E.S.L.; writing—original draft preparation, E.S.L. and J.P.; writing—review and editing, E.S.L., Y.S.L., and K.T.O.; supervision, E.S.L.; funding acquisition, E.S.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (grant number: NRF-2018R1A2B6000970).

**Conflicts of Interest:** The authors declare no competing financial interests.
