Prof. Swathi Sudhakar

Dept of Applied Mechanics and Biomedical Engineering

Prof. Swathi Sudhakar

Research Areas

Dept of Applied Mechanics and Biomedical Engineering

People

Ph. D Scholars

Kaviya V B
Shaik Sameer Basha
Thilak Raj K
Renugaa Su
Anagha Manohar
Narendren S

Post Doc

Dr. A Subastri
Dr. A Subastri

MS Scholar


Gopikasri M

Dhaksha Aniesh

Anisha Kabir

Mathana Vetrivel

Junior Research Fellow

Sachin Thomas

Mukilarasi B

Research

  • Nanotherapeutics: Development of next generation nanomaterials for the efficient treatment of Cancer, Alzheimer’s, Osteoporosis and for bone regeneration, wound healing as well as anti-microbial resistance. 
  • Single Molecule Bio-physics: Studying host-cell interactions, protein mechanics, membrane mechanics, single molecule imaging 
  • Space medicine: Investigating the effect of microgravity on cardiac, immune and bone function, development of therapeutic proteins, bone regeneration.  
  • Diagnostics: Development of diagnostic kits for Tuberculosis, Cancer and Sepsis. 

Projects

  • Exploring Nanotherapeutics for Disease Treatment and Biomedical Applications
Engineering nanomaterials to target specific cells or tissues, which allows for a precise delivery of drugs and other therapeutic agents. This leads to more effective treatments with fewer side effects.  Some of the ongoing projects in this are:  
  1. Nanochips for targeted drug delivery to control resilience in breast  cancer. <br> (In collaboration with Prof Roey Elnathan, Deakin University, Australia)  

Nanotherapeutics hold promise for eradicating cancer cells at the cellular level. We have developed reusable vertically aligned silicon hollow nanotubes (NTs) loaded with Doxorubicin-incorporated thermostable nanoarchaeosomes (NAD) for intracellular drug delivery. These NTs demonstrated a sustained drug release over 700 h, an IC50 of 60 nM against MCF-7 cells, and biocompatibility with NIH-3T3 cells. FACS analysis revealed 44.17% necrotic cell death, while angiogenesis studies showed suppression of tumour vasculature genes, highlighting the potential of NAD-loaded NTs in breast cancer therapy. 

2. Breast cancer immunotherapy – nano-vaccine 

This project focuses on developing a tumour protein-based nano vaccine that could enhance an effective immune response against breast cancer and serve as a potential therapeutic strategy to overcome adverse conditions involved in conventional cancer treatments. 

 

3. Nano-Archaeosomes for breast cancer therapeutics  

Breast cancer treatment faces challenges due to chemotherapy’s toxic side effects and the limitations of current drug carriers. Our study developed Nanoarchaeosomes (NA), highly stable nanovesicles from the archaeon Aeropyrum pernix K1, offering superior colloidal stability, biocompatibility, and high drug-loading efficiency (97%). Doxorubicin-loaded NA (NAD) showed sustained drug release for 48 hours and induced 92% late apoptosis in MCF-7 breast cancer cells with minimal cytotoxicity to healthy cells. These findings highlight NA as a promising next-generation drug carrier with enhanced therapeutic efficacy and reduced side effects. 

Read more here: https://pubs.rsc.org/en/content/articlelanding/2024/na/d3na00953j

4. Self-propulsive enzyme powered micromotors for active drug delivery 

Active colloids have been the most researched area in soft condensed matter in recent times due to their ability to replicate biomimetic motions. 

Our research interest lies in studying the kinetics of self-propelling protein-based colloidal particles in a fluid medium and elucidating their application in targeted drug delivery. 

5. Hematite nanoparticles for breast cancer therapy

Hematite (α-Fe2O3) nanoparticles, particularly in ellipsoidal (EHNP) and spherical (SHNP) shapes, show great promise as nanocarriers for cancer therapy. Our study found that EHNPs have superior cellular uptake and drug release efficiency compared to SHNPs. Cisplatin-loaded EHNPs exhibited a lower IC50 value and a four-fold increase in cell death, with G0/G1 phase arrest, compared to SHNPs. These findings suggest that ellipsoidal hematite nanoparticles offer improved biocompatibility and therapeutic efficacy, making them an attractive option for cancer treatment.

Read more here: https://pubs.rsc.org/en/content/articlelanding/2024/tb/d4tb00052h

6. Combinatorial implantable films to control multi drug resistant cancer (In collaboration with Prof Arockiarajan , Department of Applied Mech and Biomedical Engg, IIT Madras)

We developed a multifunctional PVDF membrane (MDP) loaded with Cisplatin, 5-Fluorouracil, and Doxorubicin to address multidrug resistance (MDR) in cancer treatment. The MDP membrane demonstrated biocompatibility, sustained drug release for over 72 hours, and a twofold reduction in IC50 in metastatic breast cancer cells (MDA-MB-231). It induced late apoptosis and exhibited antiangiogenic properties in a tumor microenvironment by downregulating key angiogenic markers (VEGFA, FGF2, ANG1). These results highlight its potential as an implantable therapy to prevent post-operative cancer recurrence and metastasis.

7. Design of nano-RNA-based drug delivery vehicles using organ on-chip platforms for cancer therapeutics (In collaboration with Prof Kiran Raj, Department of Applied Mech and Biomedical Engineering, IIT Madras and Dr. Shubhadeep Mandal, Department of Mechanical Engineering, IISc Bengaluru) 

The increased usage of drugs in chemotherapy results in multi-drug resistant (MDR) cancers that overexpress P- glycoprotein (P-gp) and are difficult to treat. Several studies show the usage of small interfering RNA (siRNA) for sequence-specific inhibition of P-gp mRNA as a method for overcoming MDR but is always challenged by the efficient delivery of these sensitive siRNAs. Our lab has already optimised Nanoarchaeosomes as efficient nano-carriers. This project would identify the scope of Nanoarchaeosomes as potential carriers for siRNA alongside a drug which could ultimately overcome the problem of drug resistance seen in breast cancer. The monolayer cell culture method doesn’t take into account the factors of tumor microenvironment which can be covered using 3D tumour spheroid models which are physiologically more relevant. Another problem in invitro drug target screening is that they are labour-intensive and time-consuming. These problems could be sorted by the usage of an automated droplet microfluidics-based organ-on-chip platform which will be developed in this project to achieve high throughput drug screening.

Schematic illustration representing the development and testing of nano drugs using organ-on-chip platform

• Design and Development of Advanced Biosensors for Early Disease detection

  1. Diagnostic kit for detection of cancer

 The aim of early cancer diagnosis is to identify individuals at their early stage of cancer, as soon as possible to give them the best chance survival. A lower chance of survival, more treatment-related issues, and higher cost of care are all consequences of delayed or inaccessible cancer therapy.

For delivering care at the earliest possible stage so as to increase chance of recovery, early diagnosis is inevitable. In malignant cells, glutamine has a role in energy production, redox balance, macromolecular synthesis, and signalling. It is an abundant and essential nutrient, due to these qualities, glutamine levels and its metabolism is a desirable target for novel clinical approaches to diagnose, monitor, and treat cancer. So, the research aim is to develop portable, optical biosensor to detect the L-glutamine levels in individuals, so to detect the cancer in its early stage for higher chance of survival.

2. LFA Based detection kit for TB detection

Tuberculosis (TB) remains a global health challenge, with millions of cases and deaths annually. To improve diagnosis in low-resource settings, we developed a paper-based lateral flow assay (LFA) to detect Ag85B, a key Mycobacterium tuberculosis protein. Using gold nanoparticle-conjugated antibodies, the LFA provides rapid, accurate, and affordable results without specialized training or equipment. This innovation bridges gaps in TB detection, aiding early diagnosis and reducing transmission, with strong potential for commercialization.

• Studying Phase separation in biological systems

Our lab investigates biomolecular phase separation, a process where cellular components form distinct condensates like liquid droplets or gels without membranes. This phenomenon is critical for organizing cellular activities, and its dysregulation is linked to diseases such as Alzheimer’s, cancer, and viral infections.

1. Liquid-liquid phase separation in Amyloid beta 1-40

This study explores the role of polyphosphate (polyP) in modulating amyloid beta [Aβ(1-40)] fibrilization, a hallmark of Alzheimer’s disease, revealing its pH-dependent dual effects. At neutral pH (7), polyP inhibits fibrilization in a dose-dependent manner, while at acidic pH (3), it accelerates fibrilization via liquid-liquid phase separation (LLPS), forming fibril-rich droplets. A phase diagram delineates the LLPS domain at pH 3. The findings highlight how anionic biopolymers like polyP influence amyloid aggregation, offering insights into neurodegenerative disease mechanisms.

Read more here: https://pubs.acs.org/doi/abs/10.1021/acschemneuro.3c00286iclelanding/2024/na/d3na00953j

2. Electrostatic interactions drive phase separation in Pup protein.

We developed a peptide-protein coacervate system using Poly-L-Lysine and Pup to model the electrostatic behaviour of membrane-less organelles (MLOs) via liquid-liquid phase separation (LLPS). Turbidity, optical microscopy, and fluorescence imaging highlighted the role of charge density in coacervation and confirmed the presence of both biopolymers in the droplets. This system offers insights into MLO mechanisms, origins of life, and potential therapeutic targets.

• Active Colloids

 Synthetic micro/nanomotors are gaining popularity for biomedical applications, particularly in drug delivery, as they mimic the motion of biological micro/nanoscale swimmers. These applications require precise control over propulsion speed, direction, and motion type (e.g., translation, circular), as well as self-propulsive force. We use the self-propulsion speed and force of active colloids to create efficient diffusiophoretic micro/nanomotors.

Read more here : https://www.sciencedirect.com/science/article/pii/S002197972401751X

• Space Biology

1. Development of therapeutic strategies to mitigate oxidative stress and cytoskeletal damage in astronauts for the Gaganyaan space mission

The project aims to explore the relationship between exposure to microgravity and the development of oxidative stress in astronauts, leading to weakened bones and vasculature and as a result, osteoporosis. Based on the observations, nanotherapeutic formulations are developed to combat the stress conditions, which enables the safer execution of manned space missions in the future.

 

2. Microgravity as a platform to enhance drug loading efficiency in nanomaterials.

Our research explores microgravity as a novel platform to enhance drug-loading efficiency in nanomaterials. We demonstrated a significant increase in drug loading, achieving over two-fold improvement in iron oxide nanoparticles (50.4% to 99%) and four-fold in liposomes (14.28% to 97.2%), with sustained drug release. These microgravity-engineered nanomaterials showed excellent biocompatibility and anticancer efficacy against breast cancer (MCF-7) cells. This approach offers a scalable solution to overcome current challenges in drug delivery systems. Our findings open new avenues for innovative drug delivery and space-based pharmaceutical research

Read more here : https://www.sciencedirect.com/science/article/pii/S1773224724005380

3. Effect of simulated microgravity on artificial single cell membrane mechanics.

In this project built a GUV-based simplified model for cell membrane dynamics studies in simulated microgravity. Space travel-related physiological anomalies can be studied using this model. Under microgravity condition. The vesicles appear elongated and more fluid due to increased disordered lipids. Improved cell membrane fluidity under microgravity opens new avenues for drug delivery and disease studies.

Read more here: https://link.springer.com/article/10.1007/s12217-024-10133-9

• Single molecule biophysics

1. Resolving the microtubule dynamics using single-molecule techniques

The dynamics of cytoskeletal proteins decide the underlying mechanism of neurodegenerative diseases and malignancy observed in cancerous cells. This project aims to study about the interactions observed in microtubules at the molecular level using single molecule techniques alongside computer simulations which will help in designing targeted drug delivery approaches for such diseases.   

• In-vivo tissue engineering in Animal Models

In our lab we use Zebrafish models as well as other animal models as in-vivo systems for studying potential therapeutics and understanding mechanisms of wound healing and regeneration​. The zebrafish (Danio rerio) is a valuable in vivo model for tissue engineering due to its rapid development, high reproductive rate, and remarkable regenerative abilities. Its genetic and physiological similarities to humans, along with cost-effective maintenance and transparent embryos, facilitate detailed studies on tissue repair and drug discovery.

1. Protein Nano Coop Complexes Promote Fracture Healing and Bone Regeneration in a Zebrafish Osteoporosis Model

This study developed zein nano coop composites (AZN) containing chimeric antioxidants for bone regeneration. In vitro experiments with human osteoblast-like MG63 cells showed enhanced bone mineralization and regeneration. In a Zebrafish osteoporosis model, AZN exhibited high biocompatibility, increased calcium/phosphorus deposition, and upregulated osteogenic genes. These findings highlight AZN’s potential in bone regeneration and fracture healing, with promising applications for osteoporosis treatment. Further studies in animal models are needed to validate these results and expand its therapeutic potential.

Read more here: https://pubs.acs.org/doi/full/10.1021/acs.biomac.4c00931

2. Bio-Active Wound healing patches

Advancements in wound repair therapies increasingly highlight biomaterials’ role as innovative treatment options. Bioactive electrospun nanofiber membranes made from plant-based proteins and non-digestible oligosaccharides are used for advanced wound care. Mimicking the extracellular matrix, these membranes promote tissue regeneration, moisture retention, and antimicrobial protection, addressing antimicrobial resistance in chronic wounds. The solution is biocompatible, sustainable, and effective, offering faster healing and reduced infection risks.

Facilities

 SI. No Product Name Manufacturer
1Optical MicroscopeInfinity
2PCR machineEppendorf Mastercycler
3ThermomixerEppendorf
4Cooling CentrifugeThermo Scientific
5UltrasconicatorBRBiochem Life-science
6Plate ReaderAgilent Technologies
7NanoDropThermo Scientific
8Hot air ovenThermo Scientific
9Fluorescence MicroscopeInfinity
10Biosafety cabinetThermoScientific
11CO2 incubatorThermoScientific
12Optical MicroscopeMagnus
13Microgravity simulatorCustom Built with Dr.Chatterjee’s lab
14Cryogenic vessel with Liq. nitrogen sensor)ThermoScientific
15FTIR spectrometer Thermoscientific

Instruments

Collaboration

Social Impact

Our lab also focusses on sustainable and eco-friendly innovations. We develop biodegradable materials, green nanotechnologies, and sustainable agricultural solutions to reduce environmental footprints. Through these efforts, we aim to contribute to a healthier planet and empower communities with sustainable advancements.

• Sustainability and Eco-friendly projects:

Projects in collaboration with – Prof Ethayaraja Mani (Dept of CHEM ENGG, IITM)

1. Nanoparticle for agricultural applications

Fungal diseases in agriculture are a source of concern for crop production.

Synthetic fungicides are used to protect crops, but they pollute the environment because only a small portion is absorbed by plants. To address this, we synthesized hydroxyapatite (HA) nanoparticles with PEG and loaded the nanoparticles with surfactin, a potent bio-surfactant with antimicrobial properties, to enhance the dual function of fertilizer and fungicide.

2. Development of Hematite Nano Ellipsoids/Pectin Composite Films for Green Packaging Applications

Synthetic packaging materials pose environmental and health risks, prompting the need for eco-friendly alternatives like pectin. However, native pectin films (NPF) have limitations, including poor mechanical strength and barrier properties. Our study addresses this by incorporating hematite nano ellipsoids (HNEs) into NPF, enhancing tensile strength by 35%, contact angle by 30°, oxygen barrier properties six-fold, and water vapor barrier properties by 20%. These improvements make the pectin–hematite composite a sustainable, biodegradable, and biocompatible packaging solution. This work highlights the potential of combining biopolymers and nanotechnology for greener packaging.

Read more here : https://pubs.acs.org/doi/full/10.1021/acs.langmuir.4c01095

3. Microplastic degradation using Hematite nanoparticles.

4. Edible coating to increase the shelf life of fruits - a sustainable solution

Publications

  1. Kaviya VB, Swathi Sudhakar* et al. RSC Nanoscale Advances 2024 6, 2026-2037
  2. Subastri A, Swathi Sudhakar* et al, RSC Materials Advances -2024,7, 1267
  3. Anisha K., Swathi Sudhakar*, et al.,Protein nano coop complexes promote fracture healing and bone regeneration in zebrafish osteoporosis model. 2024 Oct 24. doi: 10.1021/acs.biomac.4c00931. 
  4. Thilak Raj K, Swathi Sudhakar* et al., Direct measurement of self-diffusiophoretic force generated by active colloids of different patch coverage using optical tweezers, Journal of Colloids and Interface Science
  5. Sameer S, Kaviya VB, Anisha Kabir, Thilak Raj and Swathi Sudhakar*. Microgravity as a platform to enhance drug loading in nanomaterials. Journal of drug delivery science and technology, 2024, 98, 105869.
  6. Asuwin Prabu R G, Anagha Manohar, Narendran S, Anisha Kabir, Swathi Sudhakar*, Effect of simulated microgravity on artificial single cell membrane mechanics, Springer Microgravity Science and Technology, Elsevier, 2024, 36 (4), 1-10.

Read more : https://scholar.google.com/citations?user=grf-2csAAAAJ&hl=en

Optical Microscopy