Dr. Jeena is a chemist whose research primarily focused on exploring chemical reactions inside the live cell, creating supramolecular self-assembly inside the cellular sub-compartments and organelle membrane perturbation to alter the cellular fate for applications such as cancer therapeutics, imaging, and in-depth study of cellular metabolism. At present (2021-) she is pursuing post-doctoral training under Dr. Jianghong Rao at Stanford School of Medicine. She did PhD at Ulsan National Institute of Science and technology (2013-2018, GPA 4.11/4.9, Thesis: Organelle Localization Induced Self-assembly of Amphiphilic Peptides: A Novel Strategy for Therapeutics) under prof. Ja-Hyoung Ryu. Jeena's PhD research introduced a new concept of mitochondria localized self-assembly of small molecules as a potential strategy to induce selective cancer cell death. She received MS in Applied Chemistry from Cochin University of Science and Technology, Kerala, India (2012, score ranked second in the university) and BS in Chemistry from Payyannur Collage, Kerala, India (2010, score ranked third in the university).

Professional Education

  • Master of Science, Cochin Univ Science & Technology (2012)
  • Project Intern, National Chemical Laboratory, Pune, Polymer Chemistry (2011)
  • Summer Research, Indian Institute of Technology, Organometallic Chemistry (2011)
  • BS, Payyannur Collage, Chemistry (2010)
  • MS, Cochin University of Science and Technology, Applied Chemistry (2012)
  • PhD, Ulsan National Institute of Science and Technology, Supramolecular Chemistry, Cancer therapy (2019)

Stanford Advisors


  • Jeena Manayath Thekkeyil. "United States Patent US20180133330A1 Conjugate including peptide molecule capable of self-assembly in cell organelle and pharmaceutical composition for preventing or treating cancer including conjugate", UNIST Academy Industry Research Corp, May 17, 2018

All Publications

  • Application of self-assembly peptides targeting the mitochondria as a novel treatment for sorafenib-resistant hepatocellular carcinoma cells. Scientific reports Hong, T. H., Jeena, M. T., Kim, O. H., Kim, K. H., Choi, H. J., Lee, K. H., Hong, H. E., Ryu, J. H., Kim, S. J. 2021; 11 (1): 874


    Currently, there is no appropriate treatment option for patients with sorafenib-resistant hepatocellular carcinoma (HCC). Meanwhile, pronounced anticancer activities of newly-developed mitochondria-accumulating self-assembly peptides (Mito-FF) have been demonstrated. This study intended to determine the anticancer effects of Mito-FF against sorafenib-resistant Huh7 (Huh7-R) cells. Compared to sorafenib, Mito-FF led to the generation of relatively higher amounts of mitochondrial reactive oxygen species (ROS) as well as the greater reduction in the expression of antioxidant enzymes (P < 0.05). Mito-FF was found to significantly promote cell apoptosis while inhibiting cell proliferation of Huh7-R cells. Mito-FF also reduces the expression of antioxidant enzymes while significantly increasing mitochondrial ROS in Huh7-R cells. The pro-apoptotic effect of Mito-FFs for Huh7-R cells is possibly caused by their up-regulation of mitochondrial ROS, which is caused by the destruction of the mitochondria of HCC cells.

    View details for DOI 10.1038/s41598-020-79536-z

    View details for PubMedID 33441650

    View details for PubMedCentralID PMC7806888

  • Spatiotemporal Self-Assembly of Peptides Dictates Cancer-Selective Toxicity BIOMACROMOLECULES Jin, S., Jeena, M. T., Jana, B., Moon, M., Choi, H., Lee, E., Ryu, J. 2020; 21 (12): 4806–13


    The intracellular or pericellular self-assembly of amphiphilic peptides is emerging as a potent cancer therapeutic strategy. Achieving the self-assembly of amphiphilic peptides inside a cell or cellular organelle is challenging due to the complex cellular environment, which consists of many amphiphilic biomolecules that may alter the self-assembling propensity of the synthetic peptides. Herein, we show that the hydrophobic-hydrophilic balance of the amphiphilic peptides determines the self-assembling propensity, thereby controlling the fate of the cell. A series of peptides were designed to target and self-assemble inside the mitochondria of cancer cells. The hydrophobicity of the peptides was tuned by varying their N-terminus capping. The analysis showed that the largest hydrophobic peptide was self-assembled before reaching the mitochondria and showed no selectivity toward cancer cells, whereas hydrophilic peptides could not self-assemble inside the mitochondria. Optimum balance between hydrophobicity and hydrophilicity is a critical factor for achieving self-assembly inside the mitochondria, thereby providing greater selectivity against cancer cells.

    View details for DOI 10.1021/acs.biomac.0c01000

    View details for Web of Science ID 000599993400014

    View details for PubMedID 32865983

  • Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Kim, D., Jeena, M. T., Kim, O., Hong, H., Seo, H., Ryu, J., Kim, S. 2020; 21 (17)


    Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes.

    View details for DOI 10.3390/ijms21176126

    View details for Web of Science ID 000570370700001

    View details for PubMedID 32854415

    View details for PubMedCentralID PMC7504046

  • Intra-mitochondrial self-assembly to overcome the intracellular enzymatic degradation ofl-peptides CHEMICAL COMMUNICATIONS Jeena, M. T., Lee, S., Barui, A., Jin, S., Cho, Y., Hwang, S., Kim, S., Ryu, J. 2020; 56 (46): 6265–68


    The design of peptide-based therapeutics is generally based on the replacement of l-amino acids with d-isomers to obtain improved therapeutic efficiency. However, d-isomers are expensive and frequently induce undesirable immune responses. In the present work, we demonstrate that an intra-mitochondrially self-assembling amphiphilic peptide exhibits analogous activity in both d- and l-isomeric forms. This outcome is in contrast to the general observation considering higher therapeutic efficiencies of d-isomers compared with l-analogues. This suggests that l-peptides overcome proteolytic degradation during intra-mitochondrial self-assembly both in vitro and in vivo.

    View details for DOI 10.1039/d0cc02029j

    View details for Web of Science ID 000541419600017

    View details for PubMedID 32373826

  • Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy CANCERS Jeena, M. T., Kim, S., Jin, S., Ryu, J. 2020; 12 (1)


    The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being a critical center of metabolic activities and involved in many diseases, mitochondria have been attracting attention as a potential target for therapeutics, especially for cancer treatment. Structural and functional differences between healthy and cancerous mitochondria, such as membrane potential, respiratory rate, energy production pathway, and gene mutations, could be employed for the design of selective targeting systems for cancer mitochondria. A number of mitochondria-targeting compounds, including mitochondria-directed conventional drugs, mitochondrial proteins/metabolism-inhibiting agents, and mitochondria-targeted photosensitizers, have been discussed. Recently, certain drug-free approaches have been introduced as an alternative to induce selective cancer mitochondria dysfunction, such as intramitochondrial aggregation, self-assembly, and biomineralization. In this review, we discuss the recent progress in mitochondria-targeted cancer therapy from the conventional approach of drug/cytotoxic agent conjugates to advanced drug-free approaches.

    View details for DOI 10.3390/cancers12010004

    View details for Web of Science ID 000516826700004

    View details for PubMedID 31861339

    View details for PubMedCentralID PMC7016936

  • Heterochiral Assembly of Amphiphilic Peptides Inside the Mitochondria for Supramolecular Cancer Therapeutics ACS NANO Jeena, M. T., Jeong, K., Go, E., Cho, Y., Lee, S., Jin, S., Hwang, S., Jang, J., Kang, C., Bang, W., Lee, E., Kwak, S., Kim, S., Ryu, J. 2019; 13 (10): 11022–33


    Self-assembly of peptides containing both l- and d-isomers often results in nanostructures with enhanced properties compared to their enantiomeric analogues, such as faster kinetics of formation, higher mechanical strength, and enzymatic stability. However, occurrence and consequences of the heterochiral assembly in the cellular microenvironment are unknown. In this study, we monitored heterochiral assembly of amphiphilic peptides inside the cell, specifically mitochondria of cancer cells, resulting in nanostructures with refined morphological and biological properties owing to the superior interaction between the backbones of opposite chirality. We have designed a mitochondria penetrating tripeptide containing a diphenyl alanine building unit, named as Mito-FF due to their mitochondria targeting ability. The short peptide amphiphile, Mito-FF co-assembled with its mirror pair, Mito-ff, induced superfibrils of around 100 nm in diameter and 0.5-1 μm in length, while enantiomers formed only narrow fibers of 10 nm in diameter. The co-administration of Mito-FF and Mito-ff in the cell induced drastic mitochondrial disruption both in vitro and in vivo. The experimental and theoretical analyses revealed that pyrene capping played a major role in inducing superfibril morphology upon the co-assembly of racemic peptides. This work shows the impact of chirality control over the peptide self-assembly inside the biological system, thus showing a potent strategy for fabricating promising peptide biomaterials by considering chirality as a design modality.

    View details for DOI 10.1021/acsnano.9b02522

    View details for Web of Science ID 000492801600015

    View details for PubMedID 31508938

  • Mitochondria localization induced self-assembly of peptide amphiphiles for cellular dysfunction NATURE COMMUNICATIONS Jeena, M. T., Palanikumar, L., Go, E., Kim, I., Kang, M., Lee, S., Park, S., Choi, H., Kim, C., Jin, S., Bae, S., Rhee, H., Lee, E., Kwak, S., Ryu, J. 2017; 8: 26


    Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy. The Mito-FF fibrils induce mitochondrial dysfunction via membrane disruption to cause apoptosis. The organelle-specific supramolecular system provides a new opportunity for therapeutics and in-depth investigations of cellular functions.Spatiotemporal control of intracellular molecular self-assembly holds promise for therapeutic applications. Here the authors develop a peptide consisting of a phenylalanine dipeptide with a mitochondrial targeting moiety to form self-assembling fibrous nanostructures within mitochondria, leading to apoptosis.

    View details for DOI 10.1038/s41467-017-00047-z

    View details for Web of Science ID 000403768500002

    View details for PubMedID 28638095

    View details for PubMedCentralID PMC5479829

  • A siloxane-incorporated copolymer as an in situ cross-linkable binder for high performance silicon anodes in Li-ion batteries NANOSCALE Jeena, M. T., Bok, T., Kim, S., Park, S., Kim, J., Park, S., Ryu, J. 2016; 8 (17): 9245–53


    The electrochemical performance of Li-ion batteries (LIBs) can be highly tuned by various factors including the morphology of the anode material, the nature of the electrolyte, the binding material, and the percentage of conducting materials. Binding materials have been of particular interest to researchers over the decades as a means to further improve the cycle durability and columbic efficiency of LIBs. Such approaches include the introduction of different polymeric binders such as poly(acrylic acid) (PAA), carboxymethyl cellulose (CMC), and alginic acid (Alg) into the Si anode of LIBs. To achieve a better efficiency of LIBs, herein, we introduce a novel copolymer, poly(tert-butyl acrylate-co-triethoxyvinylsilane) (TBA-TEVS), as an efficient binder with stable cycle retention and excellent specific capacity. The binder forms a highly interconnected three-dimensional network upon thermal treatment as a result of de-protection of the tert-butyl group and the consequent inter-intra condensation reaction, which minimizes pulverization of the Si nanoparticles. Moreover, the siloxane group is expected to promote the formation of stable solid-electrolyte-interface (SEI) layers. A series of random copolymers were synthesized by varying the molar ratio of tert-butyl acrylate and triethoxyvinylsilane. Twenty-one percent of TEVS in the TBS-TEVS copolymer gave rise to a superior performance as a binder for Si anodes, where the anodes showed a stable specific capacity of 2551 mA h g(-1) over hundreds of cycles and an initial columbic efficiency (ICE) of 81.8%.

    View details for DOI 10.1039/c6nr01559j

    View details for Web of Science ID 000375285800022

    View details for PubMedID 27087685

  • The HA-incorporated nanostructure of a peptide-drug amphiphile for targeted anticancer drug delivery CHEMICAL COMMUNICATIONS Choi, H., Jeena, M. T., Palanikumar, L., Jeong, Y., Park, S., Lee, E., Ryu, J. 2016; 52 (32): 5637–40


    A simple peptide based prodrug of camptothecin (CPT) has been synthesised in which the CPT is conjugated to a tripeptide (KCK) via a disulfide linkage (KCK-CPT) and self-assembled into well-defined nanostructures in water depending on the concentration. The hyaluronic acid (HA) complex of KCK-CPT exhibited target specific toxicity with excellent antitumour efficiency.

    View details for DOI 10.1039/c6cc00200e

    View details for Web of Science ID 000374035800033

    View details for PubMedID 27034247

  • Multifunctional Molecular Design as an Efficient Polymeric Binder for Silicon Anodes in Lithium-Ion Batteries ACS APPLIED MATERIALS & INTERFACES Jeena, M. T., Lee, J., Kim, S., Kim, C., Kim, J., Park, S., Ryu, J. 2014; 6 (20): 18001–7


    This work demonstrates the design, synthesis, characterization, and study of the electrochemical performance of a novel binder for silicon (Si) anodes in lithium-ion batteries (LIBs). Polymeric binders with three different functional groups, namely, carboxylic acid (COOH), carboxylate (COO(-)), and hydroxyl (OH), in a single polymer backbone have been synthesized and characterized via (1)H NMR and FTIR spectroscopies. A systematic study that involved varying the ratio of the functional groups indicated that a material with an acid-to-alcohol molar ratio of 60:40 showed promise as an efficient binder with an initial columbic efficiency of 89%. This exceptional performance is attributed to the strong adhesion of the binder to the silicon surface and to cross-linking between carboxyl and hydroxyl functional groups, which minimize the disintegration of the Si anode structure during the large volume expansion of the lithiated Si nanoparticle. Polymers with multiple functional groups can serve as practical alternative binders for the Si anodes of LIBs, resulting in higher capacities with less capacity fade.

    View details for DOI 10.1021/am504854x

    View details for Web of Science ID 000343684200079

    View details for PubMedID 25233116