A biomimetic nano-suspension based on orthoester designed for the inhibition of postoperative tumor recurrence.

Tumor recurrence after surgery remains a major challenge. Herein, an orthoester (OE) compound was synthesized as a liquid pharmaceutical excipient. Next, an injectable suspension loaded with biomimetic nanoparticles and photothermal agents was constructed based on OE to inhibit tumor recurrence. The synthesized OE has the characteristics of simple structure, acid-sensitivity, clear degradation mechanism in vivo. More importantly, as a liquid excipient, OE can dissolve or disperse a variety of drugs, biomacromolecules or nanoparticles to form a stable suspension at extremely high concentrations. Thus, dasatinib (DAS) and sunitinib (SUN) were self-assembled to form nanoparticles, and cancer cell membrane vesicles were coated to obtain biomimetic nanoparticles (HCM@NPs). The self-assembly of DAS and SUN induces molecular aggregation, resulting in an aggregation-induced emission (AIE) effect, which facilitates the tracking of intracellular drug delivery. HCM@NPs and photothermal agent IR820 were co-dispersed in OE to obtain a synergistic therapeutic suspension (OE/IR/HCM@NPs). The suspension can be injected around the tumor or applied directly to the surgical bed to cover any suspicious areas. OE significantly improves the photothermal conversion efficiency of IR820 through its exceptionally low specific heat capacity (1.8 J/(g·℃)), which is markedly lower than that of water (4.2 J/(g·℃). In vitro and in vivo data demonstrated that the OE-based suspension directly inhibited tumor growth and prevented tumor recurrence. All mice receiving chemotherapy alone succumbed within 26 days due to tumor recurrence, whereas 66 % of those treated with the OE nano-suspension exhibited complete suppression of tumor recurrence over the observation period. This paper provides a new idea for the development of suspensions based on OE.