Abstract

BackgroundOrganic nanomaterials having specific biological properties play important roles in in vivo delivery and clearance from the live cells. To develop orally deliverable nanomaterials for different biological applications, we have synthesized several fluorescently labelled, self-assembled PABA nanoparticles using possible acid side chain combinations and tested against insect and human cell lines and in vivo animal model. Flurophores attached to nanostructures help in rapid in vivo screening and tracking through complex tissues. The sub-cellular internalization mechanism of the conjugates was determined. A set of physio-chemical parameters of engineered nanoskeletons were also defined that is critical for preferred uptake in multiple organs of live Drosophila.ResultsThe variability of side chains alter size, shape and surface texture of each nanomaterial that lead to differential uptake in human and insect cells and to different internal organs in live Drosophila via energy dependent endocytosis. Our results showed that physical and chemical properties of C-11 and C-16 acid chain are best fitted for delivery to complex organs in Drosophila. However a distinct difference in uptake of same nanoparticle in human and insect cells postulated that different host cell physiology plays a critical role in the uptake mechanism.ConclusionsThe physical and chemical properties of the nanoparticle produced by variation in the acid side chains that modify size and shape of engineered nanostructure and their interplay with host cell physiology might be the major criteria for their differential uptake to different internal organs.

Highlights

  • Organic nanomaterials having specific biological properties play important roles in in vivo delivery and clearance from the live cells

  • The p-aminobenzoic acid (PABA) nanomaterials obtained from compound 1-7 were named as C-11, C-11U, C-12, C-14, C-16, C-18, C-18U respectively, based on the length of the side chains and unsaturated moieties coupled during synthesis (Figure 1A)

  • A distinct internal cell environment of Drosophila S2 cells increase the uptake of unsaturated C-11U particles. These results demonstrated that three major factors; shape, properties associated with unsaturated side chain and cross species cell physiology are involved in the rate of cellular uptake. (Figure 2; Additional File 2 Figure S12)

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Summary

Introduction

Organic nanomaterials having specific biological properties play important roles in in vivo delivery and clearance from the live cells. To develop orally deliverable nanomaterials for different biological applications, we have synthesized several fluorescently labelled, self-assembled PABA nanoparticles using possible acid side chain combinations and tested against insect and human cell lines and in vivo animal model. Though use of nano-materials has been successful in in vitro cultured cells [10], in practice, its adaptability in in vivo organ tracking by repeated injections is more challenging because of its limited self-life, delivery hurdles, and compatibility to fragile cell environment and potent immunogenicity [11]. Major improvements on chemical modifications of nano-materials play a fundamental role in cell uptake and live tissue distribution [12]. It is mainly due to lack of self-assembled organic molecules and compatibility of small molecules with nanoskeleton [14,15,16]

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