# The direct transfer approach for transcellular drug delivery

## TL;DR

This paper reviews a new drug delivery method called direct transfer, which uses cell-to-cell contact to quickly and deeply deliver drugs into tissues.

## Contribution

The paper introduces and categorizes three distinct modalities of direct transfer for transcellular drug delivery.

## Key findings

- Direct transfer enables rapid and deep drug penetration into tissues via cell-cell contact.
- Three modalities of direct transfer are identified: membrane contact, gap junctions, and tunneling nanotubes.
- Each modality has unique structures and effectiveness for drug delivery.

## Abstract

A promising paradigm for drug administration that has garnered increasing attention in recent years is the direct transfer (DT) of nanoparticles for transcellular drug delivery. DT requires direct cell-cell contact and facilitates unidirectional and bidirectional matter exchange between neighboring cells. Consequently, DT enables fast and deep penetration of drugs into the targeted tissues. This comprehensive review discusses the direct transfer concept, which can be delineated into the following three distinct modalities: membrane contact-direct transfer, gap junction-mediated direct transfer (GJ-DT), and tunneling nanotubes-mediated direct transfer (TNTs-DT). Further, the intercellular structures for each modality of direct transfer and their respective merits and demerits are summarized. The review also discusses the recent progress on the drugs or drug delivery systems that could activate DT.