Doxorubicin-induced co-assembling nanomedicines with temperature-sensitive acidic polymer and their in-situ-forming hydrogels for intratumoral administration

Doxorubicin (DOX)-induced co-assembling nanomedicines (D-PNA x ) with temperature-sensitive PNA x triblock polymers have been developed for regional chemotherapy against liver cancer via intratumoral administration in the present work. Owing to the formation of insoluble DOX carboxylate , D-PNA x nanomedicines showed high drug-loading and entrapment efficacy via a simple mixing of doxorubicin hydrochloride and PNA x polymers. The sustained releasing profile of D-PNA100 nanomedicines indicated that only 9.4% of DOX was released within 1   day, and 60% was released during 10   days. Based on DOX-induced co-assembling behavior and their temperature sensitive in-situ -forming hydrogels, D-PNA100 nanomedicines showed excellent antitumor activity against H22 tumor using intratumoral administration. In contrast to that by free DOX solution (1.13   ±   0.04 times at 9   days) and blank PNA100 (2.11   ±   0.34 times), the tumor volume treated by D-PNA100 had been falling to only 0.77   ±   0.13 times of original tumor volume throughout the experimental period. In vivo biodistribution of DOX indicated that D-PNA100 nanomedicines exhibited much stronger DOX retention in tumor tissues than free DOX solution via intratumoral injection. D-PNA100 nanomedicines were hopeful to be developed as new temperature sensitive in-situ -forming hydrogels via i.t. injection for regional chemotherapy.