Group # 3

Complex Engineering
Problem

Asadulah Malik - Hussain Danial - Mustafa Muhammad Ali - Naeem Sultan

Present at ion
Highlights

Problem Statement
Introduction
Delivery of a Targeting Drug to Tumor Cells in the Liver Using
Nanotechnology
Detection of Tumors and Cancer Cells at Their EarlyStage by Using
Nanotechnology
Discussion
Conclusions
 Problem Statement
Nanostructures have played a tremendous role in targeted drug delivery. Unlike conventional drug
deliveries, the targeted drug delivery uses the least amount of drug and does not affect other
tissues/organs. Keeping this in view, you are required to:

How can you successfully deliver a targeted drug to tumor cells in the liver
using nanotechnology?

Also, explain that how can one detect tumors and cancer at their early stage
by using nanotechnology?
Introduction

Modern nanotechnology is an interdisciplinary science involving the smallest particles and their special
chemical, physical and mechanical properties at the junction between physics, chemistry, biology, medicine,
electronics and information technology. Nanobiotechnology deals with the intracellular and intercellular
processes of molecules, which is essential for the application of nanotechnology in medicine. This is reflected
in the various interactions between medical nanotechnology and the possible applications of
nanobiotechnology in human medicine. The expectations for the diagnostic, therapeutic and regenerative
potential of nanomedicine are huge. Their purpose is to perform rapid and inexpensive detection of genetic
susceptibility, viral infections and early signs of disease.
Applicabilty of Nano-medicine
Nanomaterials and nanoinstruments that can be used as biosensors, as a carrier of therapeutic tools and effective ingredients, and molecular
medicine knowledge or improvement in the fields of genetics,proteomics, and synthesis of microorganisms.

Nanotechnology can be used for rapid diagnosis and treatment, the recovery of genetic material and cell surgery, and the improvement of
natural physiological functions.

The view of nanotechnology and the use of nanomaterials as contrast agents in in-vivo diagnostic procedures can provide better three-
dimensional vision for images, making it easier to distinguish tissue types.
 Delivery of a Targeting Drug to Tumor Cells in the Liver
Using Nanotechnology

There are several diseases that affect the liver, including metabolic abnormalities, hepatitis, cirrhosis and cancer, of which the latter may be the most
serious. The introduction of genes or therapeutic drugs should target one of the following hepatocytes: hepatocytes, Kupffer cells and tumor
endothelial cells, or tumor cells themselves, in order to maximize the therapeutic effect and minimize systemic toxicity or non-targeting. For sexual
disease, there should be a sufficient dose or the dose must deliver a specific gene or drug to the target with minimal impact. There are potential
new treatment strategies and the clinical development of precancerous treatments for liver cancer, focusing on the use of image-guided methods to
make progress in local treatments.
Principles Strategies
Interacting with blood. Use of therapeutic systems in nanodevices.
Pulmonary Vascular Bed Filtration. Modification of viral and non-viral criterions for delivery.
Uptake by target cells and reticuloendothelial
system along with Kupffer cells. Targeting antibodies and ligands for efficiency.
Migration through endothelial cells. Retarded release of drug for specific activation.
Diffusion through the tissues and uptake by cells. oimiting of the single
path proportionality.
Zero specificity in cellular uptake and intracellular targeting.
Nanocarriers associated with
Liver Cancer Targeted or
Selective Drug Delivery
Systems

Nanobiotechnology has been used to improve drug delivery and overcome certain drug delivery challenges in cancer. They
can be divided into many categories, including the use of various nanoparticles, nanoencapsulation, targeted delivery for
various organ tumors, and combinations with other cancer treatment methods (such as radiation therapy). Nanoparticles are
also used in gene therapy of cancer. Certain technologies can achieve a combination of diagnosis and treatment, which is
essential for personalized cancer care.
Polyethylene Glycol Coated
Nanoparticles

Biodegradable PEG-coated nanoparticles can be combined with folic-acid to target folate binding proteins. This molecule is
a soluble form of the folate receptor, which is overexpressed on the surface of many tumor cells. The specific interaction
between conjugated folate nanoparticles and folate binding protein was evaluated by surface plasmon resonance, and the
binding was confirmed to folic acid. Nanoparticles are transformed into folate binding protein. Therefore, folic acid-
conjugated nanoparticles represent a potential new drug carrier targeting tumor cells, and biodegradable PEG-coated
polycyanoacrylate nanoparticles combined with transferrin may also be effective for paclitaxel delivery carriers.
Magnetic Carbon Nanoparticles

Carbon magnetic nanoparticles (CMNP) consist of spherical particles with a diameter of 40 to 50 nm, in which iron/iron
oxide particles are dispersed in a carbon-based host structure. Free doxorubicin (DOX) molecules are immobilized on the
surface of activated CMNP particles to form a CMNP-DOX conjugate. The anti-proliferative activity of doxorubicin
immobilized in the conjugate has been confirmed in the cytotoxicity test of tumor cells at organ sites. It is suggested that the
CMNP-DOX system can be used in cancer targeted drug delivery system.
Aptamer Bioconjucate
Nanoparticles

Nucleic acid ligands (aptamers) can potentially be used for drug-encapsulated controlled release polymer particles for
therapeutic use in a cell or tissue-specific manner. A poly(lactic acid)-polyethylene glycol (PLA-PEG) copolymer with
carboxylic acid terminal functional group (PLA-PEG-COOH) and PLAPEG-encapsulated rhodamine-labeled dextran
(as a model drug) was synthesized. -COOH. These nanoparticles have the following desirable properties:

Negative surface charges can minimize non-specific interactions with negative charges. Nucleic acid aptamer.
The carboxylic acid groups on the surface of the particles help covalently bond with the amine-modified aptamer.

The presence of PEG on the particle surface reduces the uptake of unselected cells and improves the half-life of blood flow.
Nanocarriers Based on Lipids

The principle of targeted drug delivery consists of long circulatingnanoparticles (such as liposomes or micelles) that accumulate in porous
cancer tissues with high phospholipase (PLA2) activity. Special lipid prodrug compounds, after exposure to PLA2, their degradation
products will become active substances, such as anti-cancer lipids and/or fatty acid derivatives. The PLA2 hydrolysate also acts as a locally
produced penetration enhancer and promotes the absorption of the released drug across the cancer cell membrane to the putative
intracellular target site. Without prior knowledge of the location and size of the tumor, anti- cancer drugs can be specifically delivered to
the tumor target. Polymerized liposomal nanoparticles (PLN) is a non-viral nanoparticle technology that includes drug delivery systems
that can be targeted and customized for chemotherapy applications.
Methodologies adopted for Liver Cancer
Targeted or Selective Drug Delivery Systems

Since we were introduced the use of "miracle drugs" to treat various diseases, he has been actively
targeting active molecules to specific areas of the body. Due to innovations in nanomedicine, interest in the
concept has greatly increased in the past few decades.
Passive Targeting

Passive targeting is achieved by loading the drug onto the nanocarrier, and the nanocarrier passively reaches the target organ. Passive
tumor targeting uses hyperpermeable cells due to their rapid blood vessel formation. This rapid blood vessel formation leads to cell
leakage, defects and impaired lymphatic drainage. Then they begin to build up in the tumor due to ineffective lymphatic drainage.This
leads to a phenomenon called the Enhanced Permeability and Retention (EPR) effect. The size and surface properties of nanomedicine
are critical for passive targeting. Nanoparticles must be smaller than 200 nm to avoid absorption by RES, and their surface must be
hydrophilic to avoid excretion by macrophages.
Active Targeting

Recent developments have led to a shift from passive goals to active goals. By conjugating the drug-loaded nano-carrier system with
tissue or cell-specific targeting ligands, active drug targeting can be achieved. Active targeting has increased the importance of
nanomedicine and can now be achieved through many specific interactions (such as ligand receptors and antibody antigens).These
specific interactions lead to the main accumulation of intramolecular nanomedicine targets.
Specific Targeting

Due to the non-specific biodistribution of drugs, traditional chemotherapy for cancer has dose-dependent
side effects. In healthy tissues-hydrophobic drug delivery and prolonged release rate. Through active
targeting, nano-drugs can specifically deliver cancer drugs to malignant cells by using various targeting
ligands related to nano-drugs.These ligands bind to specific receptors in malignant cells. Various target
ligands, such as antibodies, small molecules (folate, whose receptor is expressed on the surface of tumor
cells) or peptides (amino acid sequence [Arg-Gly-Asp], tumor αvβ3). Integrin is covalently bound to the
surface of nanoparticles in aminopyridine to actively target anticancer drugs to malignant cells. The
targeted nano-drug will adhere to the malignant cell and the drug will be released. Increasing the drug
release rate of the target nanomedicine will take longer. The duration of action of the drug at the target
site, and reduce side effects and ultimately improve patient compliance.
Detection of Tumors and
Cancer Cells at Their Early
Stage by Using
Nanotechnology

In the fight against cancer, early detection is half the battle. Nanotechnology provides new molecular contrast agents and materials
that can achieve earlier and more accurate initial diagnosis and continuous monitoring of cancer treatment. In order to detect or
diagnose cancer, nanoparticles have been put on the market in many medical tests and researches, among which gold nanoparticles
are the most commonly used in home pregnancy tests. Used in various indications in hospitals. In cancer, nanodevices are being
studied to detect blood-borne biomarkers, including cancer-related proteins circulating in tumor cells, circulating tumor DNA, and
exosomes released from tumors. The sensor can perform multiple measurements with high sensitivity and specificity.
Organic Imaging

Modern imaging technology can only detect cancer after it has caused visible changes in tissues. At this point, thousands of cells have
grown and may have transferred. And even if a tumor is visible, a tissue biopsy must be used to assess the type of tumor, malignant or
benign, and any properties that might make it susceptible to specific treatments. Although certain primary malignant tumors can be
defined as metastatic tumors, modern imaging techniques make it extremely difficult to detect the appearance of tumors from metastatic sites
and micrometastases, even if the tissues where they usually occur are known in advance. Finally, surgical removal of tumor tissue is still the
standard for the treatment of many types of tumors, and surgeons must weigh the consequences of removing healthy, usually vital tissues
and growing cancers. Ultimately,modern surgicalmethods cannot destroy cancer cells at the level of individual cells.
Organic Sensing

In vitro diagnostic equipment using nanotechnology has high sensitivity and selectivity, and can measure multiple targets at the same time.
Established manufacturing techniques (such as photolithography) can be used to create integrated wearable devices or healthcare systems.
The diagnostic device or biosensor contains a biometric element, which can determine the presence, activity or concentration of a specific
biomolecule in a solution through a biochemical reaction. This reaction can be related to, for example, the binding of an antigen and an
antibody, the hybridization of two single-stranded DNA fragments, or the binding of a capture ligand to an epitope on the cell surface.
It is used to convert biochemical events into quantitative signals, and its transduction mechanism may be affected by optical, magnetic or
electronic effects.
Lipid Biopsy and Therapy
Response Measure

Measuring the patient’s individual response to treatment during theillnessisthe basis for accurate and predictive medical care. Accurate and
disease-appropriate monitoring can optimize treatment options (for example,corrective treatment, drug combination, and dose reduction).
Preventive clinical decision-making (for example, treatment responders and non- responders, etc.) and patient stratification in clinical trials.
For the most traditional in vivo imaging, tissue biopsy, and in vitro diagnostics available for this purpose, "fluid biopsy" provides the
ability to use simple and continuous blood draws to measure response to treatment. Traditional biopsy involves the direct removal of a
small amount of tumor tissue, so it is still an invasive procedure.
Discussion

Passive Tumor Accumulation - Effective administration of anticancer drugs should ensure high accumulation in
tumors and protect surrounding healthy tissues. With the rapid growth of tumor masses, the blood vessel
network must expand rapidly to meet the needs of tumor cells for oxygen and nutrients.

Active Tumor Targetting - The EPR effect acts as a "passive tumor targeting" solution for nanoparticles and is
the cause of the accumulation of particles in the tumor area. However, EPR does not promote the uptake of
nanoparticles by cells.

Transportation Across the Tissue Barrier - Before the drug reaches the tumor site, the delivery of nanoparticles
or nano-drugs is hindered by the tissue barrier. Tissue barriers that effectively transport nano-drugs to tumor
sites include tumor matrix (such as biological barriers) and tumor endothelial barriers (such as functional
barriers). Biological barriers are physical structures or cell formations that restrict the movement of
nanoparticles.
 Conclusions
Nanotechnology has revolutionized cancer treatment methods in many ways, and is fundamentally changing treatment options. The selective detection of cancer cells,
targeted drug delivery, and overcoming the limitations of traditional chemotherapy methods have a major impact. These new active or passive targets can largely eliminate
the side effects of traditional chemotherapy drugs, thereby greatly improving survival rates. Since cancer is one of the most serious fatal diseases, the contribution of
nanotechnology to precise treatment to avoid life-threatening side effects may be actively moving towards saving lives in clinical practice. Nanoparticles are rapidly being
developed and tested to overcome certain limitations of traditional drug delivery systems, and are emerging independently as cancer treatments.

This Complex Engineering Problem focuses on the ability of nanoparticles to recognize cells using multiple strategies that have unique recognition characteristics that can
distinguish them from previous cancer treatments.It also discusses methods for delivering certain drugs into cells through nanoparticles, and proposes many successful
analysis, as well as how nanoparticles can counter theside effects of traditional therapies through tailor-made cancer treatments.
THANK YOU