Development of a new technology for intracellular delivery into adipocytes via CaCO3-based vehicles to combat chronic diseases

Project ID: SST_IMEC_15

Adipose, or fat tissue (AT) has been considered to have the principal function of a store of lipid as a source of energy. However, recent research clearly demonstrates that AT dysfunction due to excessive fat storage is implicated in several diseases, such as obesity, type 2 diabetes, and liver disease. Linking adipose tissue as a key tissue in maintaining homeostasis above and beyond energy balance.

Promising new therapeutic modalities have been proposed to activate and recruit thermogenic, energy dissipating brown and beige adipocytes. This includes a drug nuciferine, potential treatment for liver disease; TUG-891, a candidate for the treatment of Type 2 diabetes, and mitochondrial protein UCP1, which regulates energy balance in adipocytes.

These new generations of therapeutics bring additional challenges in drug delivery technologies, notably in drug stability and intracellular delivery requirements.

These new generations of therapeutics bring additional challenges in drug delivery technologies, notably in drug stability and intracellular delivery requirements.

This project aims to develop a new approach for selective intracellular delivery into the fat cells using vaterite calcium carbonate nano- and micro-sized crystals as the delivery vehicles.

Vaterite calcium carbonate crystals have emerged as effective reservoirs
for encapsulation, protection and controlled release of both low-molecular-weight drugs and macromolecules. Our preliminary experiments demonstrated effective lysosomal uptake and full decomposition of the crystals without affecting cell viability. In this project we will employ vaterite crystals as fully biodegradable vehicles for targeted intracellular delivery. Cytotoxicity and therapeutic efficacy of the formulations will be verified in vitro.

The project includes main phases:
i) synthesis and characterization of delivery vehicles,
ii) investigation of drug loading mechanisms for effective encapsulation,
iii) evaluation of intracellular uptake and delivery,
iv) assessment of cellular response in different fat cell lines such as mitochondrial function, differentiation, lipogenesis, glucose uptake,
v) verification of an approach as generic delivery tool.

The impact of this highly interdisciplinary project is in the development of a new drug delivery system and improving overall metabolic health by enhancing brown adipocyte activation for combating chronic diseases. This technology will be indispensable for adipocytes which are difficult to transfect and be valuable for new treatment strategies for lipodystrophy and cancer cachexia.

Integral supervisory team consists of the academics from the Departments of Chemistry, Biosciences and MTIF providing the PhD candidate extensive support in biomaterials, drug delivery, cell and molecular biology, diabetes, adipose physiology. Access to state-of-the-art facilities will be provided (e.g. SEM, TEM, CLSM, TGA, FTIR, Seahorse and Oroboros cell metabolism measurements, Nanolive live cell imaging and qRT-PCR gene expression facilities).

Supervisory Team:

Dmitry Volodkin , Director of Study
Prof Assoc in Physical Chemistry and Biomaterials; google scholar: H-index 47, ca 7700 citations.

Mark Christian , Supervisor
Professor in Metabolic Health, google scholar: H-index 45, ca 6500 citations.

Rebecca Dumbell , Supervisor 
Senior Lecturer in Pharmacology; google scholar: H-index 10, ca 450 citations.

John Hunt , Supervisor
Professor in Clinical Science; google scholar: H-index 50, ca 9700 citations.

For the eligibility criteria, visit our studentship application page .

This is part of NTU's 2024 fully-funded PhD Studentship Scheme.