Injectable liquid metal nanoflake hydrogel as a local therapeutic for enhanced postsurgical suppression of tumor recurrence

Abstract

Abstract Despite the great progress achieved in nanomedicine, liquid metal (LM) nanodroplets have been mostly implemented as photo-agents for tumor phototherapy. However, in the rational design and construction of LM-based nanoplatforms for chemotherapy, limitations such as low drug-loading efficiency (LE), poor water stability, sterile and sensitive surface chemistry against ligand modification, and difficult morphology control remain to be addressed. Here, a local injectable LM-doxorubicin (LM-DOX) nanoflake-imbedded hydrogel with pH-triggered drug release is developed to achieve an enhanced therapeutic efficacy for the prevention of postoperative tumor relapse. With hyperbranched poly(amido amine) (HPAA) as the ligand, the obtained LM nanodroplets presented excellent aqueous stability and a unique flaky nanomorphology, and chemotherapeutics can be facilely conjugated via Schiff-base reaction as well. Compared to LM-based nanospheres or nanorods (LMNSs or LMNRs), LM nanoflakes (LMNFs) exhibited much higher DOX loading capacity of 63.5%. Further encapsulation of LMNF-DOX within Pluronic F-127 (LMNF-DOX@Gel) was used to diminish burst drug release, achieve long-term antitumor effect, and minimize systemic toxicity. Finally, this nano-formulation was injected into the tumor resection cavity for local chemotherapy to remove the residual tumor, achieving enhanced therapeutic efficacy and biosafety than free drugs. Overall, LMNF-based hydrogel drug delivery system represents a promising candidate for postsurgical cancer treatment.