Preparation of targeted theranostic red blood cell membranes-based nanobubbles for treatment of colon adenocarcinoma.

Objectives: Designing and fabrication of theranostic systems based on nanoscale gaseous vesicular systems, named nanobubbles (NBs), attracted enormous interest in recent years. Biomimetic vesicular platform (V-RBC-M) can improve the pharmacokinetics of the prepared platform due to augmented circulation half-life, desirable biodegradability and biocompatibility and reduced immunogenicity.

Methods: V-RBC-M were used for the encapsulation of lipophilic camptothecin (CPT) in the bilayer of vesicles through top-down method, followed by filling the core of V-RBC-M with inert SF6 gas to fabricate NBs with ultrasonic contrast enhancement capability (SF6-NB-CPT). In the next step, targeted NBs were formed via decoration of MUC1 aptamer on the surface of NBs (Apt-SF6-NB-CPT).

Results: The designed bio-NBs indicated high encapsulation efficiency and the sustained release of CPT at pH 7.4. In vitro study demonstrated higher cellular uptake and cytotoxicity of Apt-SF6-NB-CPT compared to SF6-NB-CPT in MUC1-overexpressing cells (C26). In vivo antitumor efficacy of the prepared NBs on C26 bearing BALB/c mice showed greater therapeutic efficacy and survival rate for Apt-SF6-NB-CPT. In this regard, SF6-NB-CPT showed 58% tumor growth suppression while Apt-SF6-NB-CPT system provided 95% tumor growth suppression. Furthermore, echogenic capability of SF6-NB-CPT was demonstrated through in vitro and in vivo ultrasonic imaging.

Conclusions: Our finding demonstrated that the prepared targeted NBs are a promising theranostic platform with effective therapeutic and diagnotic potentials.