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

ABSTRACT

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.

ABSTRACT

KEYWORDS:

• Red blood cell membrane
• camptothecin
• nanobubbles
• MUC1 aptamer
• theranostics

Disclosures statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Mashhad University of Medical Sciences (Grant no: 990120).