# Cell membrane disruption and recovery for intracellular delivery

> **NIH NIH R35** · UNIVERSITY OF COLORADO · 2021 · $368,025

## Abstract

PROJECT ABSTRACT
Intracellular delivery plays an essential role in biological research and therapeutic applications, however, efficient
intracellular delivery of exogenous compounds and macromolecular cargo remains a long-standing challenge.
The complex mechanisms of established methods and their often unpredictable impact on cell behaviour have
dramatically limited the scope of biological experiments and reduced efficacy of potentially promising cell therapy
concepts. Membrane disruption-based approaches have emerged as key strategies for rapid, direct and
universal intracellular delivery because they are less dependent on cargo properties and cell types, being able
to deliver almost any submicron material dispersed in solution. The ability to rapidly switch membrane-perturbing
effects on and off provides an additional level of control, enabling temporal manipulation and rapid, almost
instantaneous delivery. However, key challenges of membrane disruption strategies have been: 1) inconsistent
level of plasma membrane injury (which would lead to low viability and efficiency); 2) poor throughput or
scalability (e.g. microinjection); and 3) inadequate understanding of plasma membrane disruption and recovery
response. The PI's research group at University of Colorado Boulder centers on interdisciplinary research at the
frontiers of Biology, Medicine, Physics, and Micro/Nano Engineering. The main research thrust in the PI's group
is to develop new technologies to quantitatively understand cell membrane disruption and recovery, and explore
its application for next generation precise intracellular drug delivery. The goals for the next five years are to i)
develop a novel microfluidic platform, including NanoEngineered Surface Technology and Acoustofluidic devices,
that can precisely generate uniform and homogenous disruptions at cell membrane with controllable number and
size of the pores, to quantitatively understand cell membrane disruption and recovery dynamics at molecular,
cellular, proteiomic and high throughput level; ii) demonstrate a precise intracellular drug delivery system with
controllable dose, minimum toxicity, maximum efficiency, and high throughput, providing insight for or promoting
the next generation intracellular drug delivery. So far, biologists have not applied the fundamental insights
gleaned from membrane disruption and repair studies toward engineering cell permeability. The proposed
research grogram will bridge the scientific gap between these two disparate fields: the engineering of intracellular
delivery approaches; and the cellular mechanobiology of plasma membrane disruption and repair response. The
biomedical research community would benefit greatly from a more mechanistic and transparent understanding
of intracellular delivery, both to further the development of more robust techniques and to realize key medical
and industrial applications.
1

## Key facts

- **NIH application ID:** 10275502
- **Project number:** 1R35GM142817-01
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Xiaoyun Ding
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $368,025
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275502

## Citation

> US National Institutes of Health, RePORTER application 10275502, Cell membrane disruption and recovery for intracellular delivery (1R35GM142817-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10275502. Licensed CC0.

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