Date of Award

December 2016

Degree Type


Degree Name

Doctor of Philosophy (PhD)


Biomedical and Chemical Engineering


Shikha Nangia

Second Advisor

Shalabh C. Maroo


chemotherapeutics, cytotoxic protein, drug design, molecular dynamics, nanocarrier

Subject Categories



Efficient delivery of different drugs is a major challenge for the design of novel anticancer therapeutics because of factors such as poor drug loading capacity, ineffective shielding of the drug in the core, size distribution, and lack of desired physicochemical properties. A promising solution is for the drug delivery system to utilize polymeric micelles that can encapsulate anticancer drugs in their cores and form stable self-assembled nanocarriers. Theoretical investigations of these systems can provide insights into the chemical interactions that contribute to nanocarrier stability. However, simulations of the nanocarriers are challenging because of the computational limitations associated with the system size. In this work, multiscale computational approach was used in conjunction with collaborative laboratory experiments to analyze the role of the individual building blocks in the self-assembly of a telodendrimer, a highly tunable copolymer. The multiscale approach involves performing molecular dynamics simulations of the self-assembly of telodendrimers and approved anticancer drugs to capture micelle formation and drug encapsulation; this step is followed by reverse mapping to atomistic representation for structural analysis. First, I investigated the tunablility of the telodendrimer platform to deliver the chemotherapeutic drugs paclitaxel (PTX) and doxorubicin (DOX). The computational results were in good agreement with experimental data and showed how subtle changes in the molecular architecture of the telodendrimer’s head groups have profound effects on the nanocarrier size, morphology, and asphericity. Since cytotoxic proteins can perform more efficiently in anticancer drug delivery, using this multiscale computational approach, I next investigated the performance of another generation of telodendrimer family to deliver a cytotoxic protein, truncated diphtheria toxin (DT390) to destroy malignant cancer cells in the brain. This study described how different arrangements of this tunable telodendrimer’s building blocks change encapsulation of DT390, drug loading ratios, size distribution, biocompatibility, and stability. This work emphasizes the potential role of molecular simulations to the rational design of nanocarriers, thereby eliminating the trial and error approaches that have been prevalent in experimental synthesis. The molecular-level insights gained from these simulations will be used to design the next generation of drug-specific nanocarriers.


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