1) The document describes a study on using mesoporous metal-organic frameworks (MOFs) as nanocarriers for controlled drug release in chemotherapy. Zirconium-based MOF nanoparticles were synthesized to carry and release doxorubicin and cisplatin. 2) The MOF nanoparticles were found to have high drug loading capacity and provided controlled release of the chemotherapeutic drugs through their porous structure. In vitro tests showed the drugs were effectively released and reduced cancer cell viability. 3) The results suggest mesoporous MOFs have potential as nanocarriers for chemotherapy by improving drug pharmacokinetics and maximizing effectiveness through controlled release at tumor sites.

1. Mesoporous Metal-Organic Frameworks Serve as Nanocarriers: Controlled
Drug Release for Chemotherapy
Abel Ressom 1
, Yuan Liu, Ph.D.1
, Xiaoyuan (Shawn) Chen, Ph.D.1
Theranostic Nanomedicine Section for LOMIN; 1
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
The nanoformulation of Zirconium-based porphyrinic MOF
(ZrMOF) nanoparticles (NPs), conveying doxil or doxorubicin
(DOX) and cisplatin (CPT) being the chemo-agents used as
cargo through drug-loading, was performed in efforts to refine
the respective rate of bioavailability (BA). These NPs possess
a porosity which provides for the mediation of the delivered
medication and the benefitted development of the patient’s
biological activity.
We believe that at this potentiality—coupled with applying mesopores to the
nanoscale MOF (NMOF) synthesis of these biomaterials—the utilization of a
more precise approach in releasing proper dosages will suffice.
Nanotechnologies such as this which form these pored-MOFs remain to be the
core focus in this analyzation and of others studying nanomedicine and
biomedical engineering around the world.
Introduction
Porosed, biocompatible metal-organic frameworks have formerly been
deployed as efficient drug-delivery systems
(DDSs) to enhance pharmacokinetics and
theranostics. However, regarding CTx
(chemotherapy) the convenience of these
nanocarriers (NCs) that transport
chemotherapeutic drugs into the human body
render to maximize adherence and ensure cost
-effectiveness, i.e. lower the price.
Several significant biopharmaceutical companies
are still developing ways to implement coordination chemistry and
nanoparticle-technology into medical practice as data suggests that this field
of drug-delivery is growing almost exponentially. We posit that this clinical
technique is pragmatic, especially for chemo-, and a few biologic therapies.
Likewise, diseases or cancers such as diabetes mellitus or glioblastoma (GBM)
multiforme—which ultimately enforce inpatients to exhibit complications
subsequent to treatment—treated with chemotherapeutics permits controlled
-release through permeation, due to pore-sizing, as a viable option.
Background
The aim of this piece of research is to design and test this mesoporous
material, (2-50nm in accordance to IUPAC) DDS given the capability of
carrying the chemo drug, and the critical aspect accompanied by controlling
drug-release.
• Use UiO-66 to synthesize the ZrMOF;
• Model the morphological shape and
assess the overall pharmacotherapeutic
efficacy of the ZrMOF;
• Actively drug-load the ZrMOFs to understand its
encapsulation efficiency and quantify the
loading capacity.
Engineering Objective
Conclusion and Discussion
To conclude, the advantages of this nanotech for drug-releasing kinetics are:
• High-volume and large surface area in order to load/deliver drugs;
• Effective cell/tissue permeability;
• Low levels of cytotoxicity.
For future directions, some implications could directly be linked to cancer-
based theragnostics for bone tumors, colon cancer, hepatic cancer,
adenocarcinoma, etc.
In addition, one could go past diagnosis and therapy modalities. Indirectly
speaking, applications range from nanoelectronics that hoist sensors of smart-
materials to molecular nanotechnology/nano-systems technology (MNT) where
nanobots equipped with mini bio-machines aid mechanosynthetic processes.
References
• Krukiewickz, Katarzyna et.al, 2016. Biomaterial-based regional chemotherapy: Local anticancer drug
delivery to enhance chemotherapy and minimize its side-effects. Mater. Sci. Eng. C 62.
• Liu, Yuan et.al, 2019. Bioengineering of Metal-organic Frameworks for Nanomedicine. Theranostics; 9
(11):3122-3133. doi:10.7150/thno.31918.
• Senapati, Sudipta et.al, 2018. Controlled drug delivery vehicles for cancer treatment and their
performance. Nature News. Journal contribution.
• He, Zhimei et.al, 2019. A Catalase‐Like Metal‐Organic Framework Nanohybrid for O2‐Evolving Synergistic
Chemoradiotherapy. Angew. Chem. 131, 8844.
Acknowledgements
Special thanks to my mentor & PI, the National Institute of Biomedical Imaging
and Bioengineering (NIBIB), the Office of Intramural Training & Education
(OITE)—for providing the funding and support for my participation in the
HiSTEP 2.0 program, HHS, and the National Institutes of Health (NIH).
Methodology
Results
This flowchart displays the methods to this biophysical
analysis, which was effectuated using the following:
• TEM Machinery;
• Confocal Microscope;
• Fluorometer;
• X-Ray Diffractometer;
• Cell Viability Assay.
DOX (Left)
CPT (Right)
 Zr-Base Core/Cluster: Zr6(μ3-O)4(μ3-OH)4
Void Volume = 25.1 μM/g
Apoptosis
• Fig. A, displays the ZrMOF
polymerized (with polyacrylic
acid) to bind CPT, and Fig. B,
also has the ZrMOF plus a
polymer (polyethylene glycol)
coat, except an insertion of DOX.
• Fig. C, exhibits a colorimetric
(MTT) assay where CPT-induced
HGBCC cells prove to possess the
higher viability, whereas DOX
does better and executes more
cell-destruction.
• Fig. D, confocal laser-scanned
images taken using the U87-MG
cell line and targeting the
nucleus; (i) is the experimental
set w/ DOX-loaded and (ii) is the
control.
• For these two X-Ray
Diffraction graphs, the
indexes of the XRD peaks
are of significance.
• The two—both the UiO-
66 and ZrMOF—are
assessed to verify of
crystallinity. Since each
of these graphically
experience no round/
shallow peaks (halos),
then none of them are
amorphous. Hence, they
are said to be crystalline.
D
• Fig. A, the decrease in hydrogen-ion
concentration lets the DOX enter as the R
groups and side-chains get cleaved.
• Fig. B, photo of the loaded DOX within the
UiO-66, the premature ZrMOF: (I) poly-DOX
becomes a prodrug and (II) DOX gets
bioconjugated; homogenous mix.
• Fig. C, fluorescent intensity test on DOX
alone and a combination of UiO-66 + PEG +
DOX. The red-curve is fairly normalized,
meaning that the absorbance remains
leveled.
1)
2)
3)
• Fig. A, glutathione (GSH)
snips the NP free and grad-
ually liberates the CPT, in
this diagrammatic example.
Then, programmed cell
death—of U87-MG—
commences.
• Fig. B, an added supply of GSH
black-plot manifests a 70%
release-rate effectivity, almost a
two-fold increase from the red-
plot or no GSH, ~35%. Thus,
more CPT is given off than
wasted, so the yield of the CPT
initially encapsulated is elevated.
• Fig. C, without PAC (polyanionic
cellulose) the CPT isn’t as
effective in killing the U87-MG
cells. With this polymeric coating
no untimely, unwanted leakage
of U87-MG occurs.
• In this depiction the EPR
(enhanced permeability
and retention) effect is
shown, in which the NPs
furnish the drug-cargo
through passive targeting,
and in this instance in the
brain.
Method for
Drug-Ingress
(Route of Entry
depends)
 Metal-organic Polyhedron
D i)
ii)
• A
TEM
picture