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. 2018 Feb 27;8(16):8626-8630.
doi: 10.1039/c8ra00134k. eCollection 2018 Feb 23.

Exploring the trans-membrane dynamic mechanisms of single polyamidoamine nano-drugs via a "force tracing" technique

Siyuan Zhou  1 , Boyu Yang  1 , Yang Chen  1 , Qingrong Zhang  1 , Mingjun Cai  2 , Haijiao Xu  2 , Guocheng Yang  1 , Hongda Wang  2   3 , Yuping Shan  1
Affiliations

Exploring the trans-membrane dynamic mechanisms of single polyamidoamine nano-drugs via a "force tracing" technique

Siyuan Zhou et al. RSC Adv. .

Abstract

Considerable technological success has been achieved in the drug delivery of nano-drugs for chemotherapy, but the main obstacles in understanding the drug delivery dynamic mechanisms for nano-drug applications stem from technical limitations. In this paper, we explored the trans-membrane dynamic processes of polyamidoamine nano-drugs via a "force tracing" technique.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. A schematic representation of the chemical conjugation and physical encapsulation of MTX with PAMAM. G8-PAMAM encapsulated MTX molecules in the interior cavity of the PAMAM. MTX molecules were connected to the surface of the G4-PAMAM sphere with covalent bonds.
Fig. 2
Fig. 2. A diagram of the AFM tip chemical modification and the “force tracing” technique. (A) The nano-drug, PAMAM-MTX, is conjugated to the AFM terminal via a heterobifunctional crosslinker. (B) A schematic of the “force tracing” workflow.
Fig. 3
Fig. 3. The dynamic parameters of the trans-membrane process for G8-PAMAM-MTX obtained via the “force tracing” technique. (A) A typical trans-membrane “force tracing” curve of G8-PAMAM-MTX, where the red arrow represents a clear endocytosis force signal. (B) The histogram of the endocytosis duration for G8-PAMAM-MTX. (C) The histogram of the endocytosis forces for G8-PAMAM-MTX (n ≈ 200).
Fig. 4
Fig. 4. Block and control experiments. (A) The probability of force signals for the drug delivery of G8-PAMAM-MTX before (control) and after inhibitor treatment; the percentage was calculated using a random selection of curves chosen from thousands of “force tracing” curves. The data used are the average values of three sets of independent experimental measurements, and 1000 force curves were analysed for each single set. The values are represented as mean ± SD. (B) Typical “force tracing” curves obtained using the PEG-modified AFM tip (PEG) and unmodified AFM tip (clean tip) on normal Vero cells, and using the G8-PAMAM-MTX modified AFM tip on the Vero cells pretreated with inhibitors (CB, CPZ, M-β-CD, Nystatin, EIPA, and Filipin).
Fig. 5
Fig. 5. The dynamic parameters of the trans-membrane process for G4-PAMAM-MTX investigated using the “force tracing” technique. (A) A representation of a typical “force tracing” curve of G4-PAMAM-MTX; the red arrow is a clear endocytic force signal. (B) The histogram of the endocytic duration. (C) The histogram of the endocytic forces (n ≈ 200).
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