Comparison of the cellular uptake of P-THP—the poly(hydroxypropylmethaacrylamide [HPMA]) conjugate of pirarubicin (THP)—and P-DOX (HPMA polymer-DOX conjugate) by human pancreatic cancer cells (SUIT-2) in vitro. (A) Polymeric P-THP shows a far greater uptake by tumor cells compared with P-DOX: at 30 min, P-THP had a 33.2-fold higher uptake, and its cytotoxicity had greatly increased (see Table at lower left). (B) Penetration of P-DOX, DOX, P-THP, and THP into spheroidal tumor colon cancer (Adapted with permission from ref. [39,40]. 2016 American Chemical Society, 2019 American Chemical Society). Far greater penetration of P-THP into the tumor spheroid (similar to Figure 2, Table) is seen.