While cancers have no known cure, some of them can be successfully treated with the combination of surgery and systematic therapy. In general, systemic/widespread chemotherapy is usually injected into the bloodstream to attempt to target cancer cells. Such procedure often imparts devastating side effects because cancer drugs are nonspecific in activity, and transporting them throughout the bloodstream further reduces their ability to target the right region. This means that they kill both healthy and unhealthy cells. It has been observed that the physiological conditions of the fluids around living cells can be characterized by pH, and the magnitude of pH around a living cell is different from cancerous cells. Moreover, a multiscale anatomy of carcinoma will reveal that the microstructure of cancer cells contains some characteristic elements such as specific biomarker receptors and DNA molecules that exclusively differentiate them from healthy cells. If these cancer specific ligands can be intercalated by some functional molecules supplied from an implantable patch, then the patch can be envisioned to serve as a complementary technology with current systemic therapy to enhance localized treatment efficiency, minimize excess injections/surgeries, and prevent tumor recurrence. The broader objective of our current research is to capture some fundamental insights of such drug delivery patch system. It is envisioned that the essential components of the device is nanodiamonds (ND), parylene buffer layer and doxorubicin (DOX) drugs. In its simplest form, self-assembled nanodiamonds - functionalized or pristine, and DOX molecules are contained inside parylene capsule. The efficient functioning of the device is characterized by its ability to precisely detect targets (cancer cells) and then to release drugs at a controlled manner. The fundamental science issues concerning the development of the ND-based device include: 1. A precise identification of the equilibrium structure and self assembled morphology of nanodiamonds, 2. Fundamental understanding of the drug adsorption and desorption process to and from NDs, and 3. The rate of drug release through the parylene buffers. The structure of the nanodiamond (ND) is crucial to the adsorption and desorption of drug molecules because it not only changes the self-assembly configuration but also alters the surface electrostatics. To date, the structure and electrostatics of NDs are not yet well understood. A density functional tight binding theory (DFTB) study on smaller [2] NDs suggests a facet dependent charge distributions on ND surfaces. These charges are estimated by Mulliken Analysis [1]. Using the charges for smaller NDs (∼valid for 1–3.3 nm dia ND) we first projected surface charges for larger (4–10 nm) truncated octahedral nanodiamonds (TOND), and it has been found that the [100] face and the [111] face contain positively and negatively charged atoms, respectively. These projected charges are then utilized to obtain the self assembled structure of pristine TONDs from Molecular Dynamics (MD) simulations [4] as shown in Fig. 1. The opposite charges on the [100] and [111] face invoked electrostatic attractions among the initially isolated NDs and a network of nanodiamond agglutinates are formed as evidenced in Fig. 1(b). This study confirms why as manufactured NDs are found in agglomerated form. The study also suggests that a large fraction of ND surfaces become unavailable for drug absorption as many of the [100] faces are coherently connected to [111] faces. As a result, it can be perceived that effective area for drug adsorption on ND surfaces will be less compared to theoretical prediction which suggests that a 4nm TOND may contain as high 360 drug molecules on its surface [5]. It has been observed that as manufactured NDs may contain a variety of functional groups, and currently, we are studying the mechanism of self-assembly for functionalized nanodiamonds so that we understand the role of functional groups. The next phase of calculation involves binding of the DOX to the NDs. Essentially, the understanding of drug absorption and desorption profile at a controlled rate to and from NDs is the most critical part of the device design. Some recent quantum calculation suggests that part of NDs and drug molecules contain opposite charges at their surfaces; it has been a natural interpretation that interactions between ND and drug molecules should be straight-forward — NDs should attract to drugs as soon as they come closure. Recent experiments [6], however, suggest that NDs usually do not interact with drug molecules in the presence of neutral solutions. Addition of NaCl in the solution improves the interaction dramatically. In the first part of the study, we [3–5] have studied the interaction of single DOX molecules with TOND surfaces via MD simulation. As shown in Fig. 2, this study suggests that DOX molecules first arrange them around the preferential sites on nanodiamonds (e.g. around the [111] face) and then spontaneously attach on the surface. It is also observed that only DOX molecule is attached per facets of TONDs. It can be noted that each TOND has 6 [100] face and 8 [111] faces. Figure 3 shows the energy minimization process during the DOX-ND interaction. It can be noted that these simulations have been performed in vacuum environment. In order to see how DOX interacts in solution media, another set of simulations have been conducted where “vacuum” environment have been replaced with solution media of different pH. Moreover, functionalization on the ND surfaces will create a different environment for the DOX molecules. Research is underway to capture the fundamental physics on the DOX loading and release to and from functionalized nanodiamonds. Once we understand the essential physics of drug loading and unloading, in the future we plan to model diffusion controlled drug release through ND coated film device by incorporating the multiscale science learned from the current study. Results from this study will provide fundamental insight on the definitive targeting of infected cells and high resolution controlling of drug molecules.
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