Proof-of-Concept Multistage Biomimetic Liposomal DNA Origami Nanosystem for the Remote Loading of Doxorubicin

Abstract

One of the most promising applications of DNA origami is its use as an excellent evolution of nanostructured intelligent systems for drug delivery, but short in vivo lifetime and immune-activation are still major challenges to overcome. On the contrary, stealth liposomes have long-circulation time and are well tolerated by the immune system. To overcome DNA origami limitations, we have designed and synthesized a compact short tube DNA origami (STDO) of approximately 30 nm in length and 10 nm in width. These STDO are highly stable ≥48 h in physiological conditions without any postsynthetic modifications. The compact size of STDO precisely fits inside a stealthy liposome of about 150 nm and could efficiently remotely load doxorubicin in liposomes (LSTDO) without a pH driven gradient. We demonstrated that this innovative drug delivery system (DDS) has an optimal tumoral release and high biocompatible profiles opening up new horizons to encapsulate many other hydrophobic drugs.

An Effective Multi-Stage Liposomal DNA Origami Nanosystem for In Vivo Cancer Therapy

“…The original data were published by our group in Palazzolo et al [17]. Briefly, STDO was assembled in a one-step reaction.…”

“…Unfortunately, the liposomal system has certain limitations such as reaching an efficient drug loading only with weak base or acid molecules. Therefore, to overcome these limitations and improve the DNA nanostructure limitations (biodegradation and immune system activation), our group developed, for the first time, a robust bullet biomimetic system by making short tube DNA origami (STDO) of approximately 30 nm in length and 10 nm in width with high stability in physiological conditions for up to 48 h [17]. The compact size of STDO precisely fittted inside a stealthy liposome of about 150 nm and doxorubicin was efficiently remote loaded in liposomes (LSTDO).…”

“…The LSTDO system had a controlled release at pH 7.4 with an increased release rate in acidic conditions (pH 5.5) typical of the tumor microenvironment. LSTDO also improved the biocompatibility of DNA origami injected into immunocompetent mice (FVB/N) [17]. Therefore, there was a need to test the system (LSTDO) in vivo in order to determine if it could be used in clinics for a better cancer therapy.In this work, we studied the LSTDO remotely loaded with doxorubicin for in vivo applications.…”

Advances in DNA Origami–Cell Interfaces

“…Another method of increasing stability under physiological conditions was developed by Palazzolo and co‐workers involved the use of a short‐tube DNA origami (STDO) nanostructure that was highly stable against nucleases, as determined from an incubation assay with 10 % FBS . The authors then encapsulated DOX‐loaded STDO inside a lipid bilayer vesicle (LSTDO) using membrane extrusion.…”

“…Another methodo fi ncreasing stabilityu nder physiological conditions was developed by Palazzolo and co-workers involvedt he use of as hort-tube DNA origami (STDO) nanostructure that was highly stable against nucleases,a sd etermined from an incubation assay with 10 %F BS. [26] The authors then encapsulated DOX-loaded STDO inside al ipid bilayer vesicle (LSTDO) using membrane extrusion.M ice treated with STDO elicited am uch greater inflammatoryr esponse than those treated with LSTDO or liposomes alone, which was inferred from ELISA tests on mousep lasma on many differentc ytokines. The property of immune response avoidance combined with high drug/lipid ratio makes this system ag ood candidate for clinical applications.…”