PROBLEM:

Lung cancer has been the leading cause of cancer-related deaths worldwide for decades, significantly impacting public health. Despite explosive growth in research over the last two decades, morbidity and mortality rates remain high, with nearly 2.2 million diagnoses and 1.8 million deaths annually. Current treatments like chemotherapy and radiation have limited effectiveness and often cause severe side effects, highlighting the urgent need for alternative therapeutic approaches to improve long-term survival.

Nanomedicine has emerged as a promising solution, offering targeted drug delivery, enhanced immune response, and improved early detection. By leveraging nanotechnology, researchers aim to develop more precise treatments that selectively target cancer cells while minimizing damage to healthy tissues. This raises key questions:

• How can nanotechnology be used to target lung cancer more precisely?
• What impact could it have on treatment efficacy and patient outcomes?
• What are the advantages and disadvantages of utilizing nanomedicine, both in a general sense and specifically for lung cancer?

 

HYPOTHESIS:

I hypothesize that if nanotechnology is applied to the treatment and early detection of lung cancer, it will significantly improve the precision and effectiveness of treatment while diminishing side effects. This approach will enable more targeted drug delivery directly to cancer cells, reducing harm to healthy tissues and improving treatment outcomes.

Additionally, nanotechnology can be utilized for more accurate and earlier detection of lung cancer, allowing treatment to begin at earlier, more treatable stages. The use of nanoparticles in diagnostic imaging could enhance the detection of small, hard-to-identify tumors, increasing the chances of success. As a result, patients may experience higher survival rates, fewer recurrences, and an overall improved quality of life.

Moreover, nanomedicine could also enhance combination therapies by improving the delivery of chemotherapy, radiation, or immunotherapy, making them more effective with fewer adverse effects. Nanoparticles can be engineered to respond to specific tumor environments, releasing drugs only when they reach cancerous tissues, which minimizes toxicity. 

Overall, I believe that through further research and development, nanotechnology could revolutionize the way lung cancer is treated, making it a more personalized and effective approach for such a fatal disease.

 

For this project, no experiment is required, as my research focuses on exploring various aspects and factors of nanomedicine for lung cancer. I am gathering information by reviewing scientific articles, reputable websites, and clinical trials to understand the foundations behind nanomedicine and how it works in cancer treatment. By analyzing different sources, I aim to develop a comprehensive understanding of its mechanisms, effectiveness, and potential future applications. 

 

NANOMEDICINE

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WHAT IS IT:

Nanomedicine is the medical application of nanotechnology, focusing on the use of nanoscale materials (1 to 100 nanometers) to diagnose, treat, and prevent diseases. By working at the molecular and cellular levels, nanomedicine enables highly precise interventions, such as delivering drugs directly to diseased cells while sparing healthy tissues. This approach minimizes side effects and enhances treatment efficacy.  

Applications of nanomedicine include targeted cancer therapies, advanced diagnostic tools, and regenerative medicine. For example, nanoparticles can be engineered to deliver chemotherapy drugs directly to tumors, improving outcomes and reducing toxicity. Nanomedicine’s promise lies in its ability to transform healthcare through more effective, personalized, and minimally invasive solutions for complex diseases.

• An average human hair is about 60,000–100,000 nanometers wide

DIFFERENT APPLICATIONS:

DIAGNOSTICS AND IMAGING

Nanomedicine has significantly enhanced medical diagnostics and imaging techniques:

• Nanoparticle-based diagnostic imaging improves the sensitivity and accuracy of MRI, CT scans, and PET scans
• Highly sensitive biosensors can detect low levels of biomolecules in bodily fluids, enabling early disease detection
• Nanopore sequencing allows for rapid and accurate diagnosis of genetic disorders
• Lab-on-Nanoparticles devices perform multiple functions, including diagnostics and real-time health monitoring

TARGETED DRUG DELIVERY

Nanomedicine has transformed drug delivery systems:

• Nanocarriers can deliver therapeutic drugs directly to focal areas, increasing drug concentration at target sites while minimizing side effects
• Cancer treatment has benefited significantly from nanoparticle-based drug delivery, reducing the toxic effects of chemotherapy

THERANOSTICS

Nanotheranostics combines therapeutics and diagnostics in a single formulation:

• It allows for monitoring drug distribution, visualizing triggered drug release, and assessing treatment efficacy over time
• This approach helps in patient preselection, predicting therapeutic responses, and longitudinal monitoring

REGENERATIVE MEDICINE

Nanomedicine plays a crucial role in tissue engineering and regenerative medicine:

• Novel nanomaterials can mimic the crystal mineral structure of human bone or be used as restorative resin for dental applications
• Researchers are exploring ways to grow complex tissues, with the ultimate goal of growing human organs for transplant
• Graphene nanoribbons show promise in helping repair spinal cord injuries

DISEASE TREATMENT/PREVENTION

Nanomedicine offers innovative approaches to treating and preventing various diseases:

• Nanoparticles that mimic HDL (good cholesterol) are being studied to shrink plaque in arteries, potentially treating atherosclerosis
• Nanomaterials are being developed for use in minimally invasive surgical procedures

HOW DOES IT WORK?

Consider nanomedicine as follows: Researchers work to create and engineer atoms and molecules to act as minuscule, incredibly accurate instruments inside your body. For instance, nanomedicine can deliver medications to your body in a highly focused manner since it works on such a small scale.

• Essentially it's utilizing nanoscale materials and technologies to engage in molecular and cellular interactions with biological systems.

GENERAL SENSE

Nanoparticles are utilized for nanomedicine treatments by accurately delivering drugs to tumors/unhealthy cells. Tumors often have disordered and leaky blood vessels growing within and around them, which allow chemotherapy drugs to enter easily. However, because chemotherapy molecules are so small, they tend to diffuse through these vessels and leak out of the tumor, attacking surrounding healthy tissues. On the contrary, nanoparticles get trapped within the tumors as they are larger, allowing them to effectively concentrate on solely their job and minimize damage to healthy cells.

Targeting particular markers present only on tumor cells, nanoparticles are injected into the circulation. To guarantee that the medication is precisely administered to the damaged site without endangering nearby tissues, they stay in circulation until they bind to the tumor. This focused approach decreases side effects frequently linked to conventional chemotherapy and improves drug delivery. The safety and effectiveness of the nanoparticles in treating cancer can be further improved by engineering them to decompose into neutral byproducts after releasing their drug payload.

TARGETED DRUG DELIVERY

Nanoparticles are engineered to carry drugs directly to specific cells, such as cancerous cells in lung tumors. These nanoparticles can be coated with molecules that recognize and bind to receptors on the target cells, ensuring the drug is released only at the desired site. 

• This approach minimizes harm to healthy tissues and enhances treatment efficacy.

EARLY DETECTION 

BIOMARKERS WITH NANOPARTICLES:

• Biomarkers are molecules (proteins, DNA, RNA, or metabolites) that signal the presence of a disease. For example, in lung cancer, elevated levels of specific proteins like carcinoembryonic antigen (CEA) or fragments of circulating tumor DNA (ctDNA) in blood can indicate early stages of the disease.
• Gold nanoparticles, quantum dots, or magnetic nanoparticles are functionalized with ligands or antibodies that bind to these biomarkers with high specificity. Their small size ensures that even trace amounts of biomarkers can interact with the nanoparticles, leading to amplified signals detectable by techniques like surface-enhanced Raman scattering (SERS) or fluorescence.

ENHANCED IMAGING THROUGH NANOPARTICLES:

• Traditional imaging techniques like MRI or CT scans often struggle to detect small lesions or tumors. Nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs) or gold nanorods, are used to improve imaging resolution.
• These nanoparticles accumulate preferentially in diseased tissues due to enhanced permeability and retention (EPR) effects. 
• Cancerous tissues often have leaky vasculature, allowing nanoparticles to penetrate and remain in the tumor microenvironment. Once there, they either absorb radiation (CT imaging) or alter local magnetic fields (MRI), generating clearer, more detailed images.

QUANTUM DOTS FOR DETECTION

• Quantum dots (QDs) are semiconductor nanocrystals 
• They emit specific wavelengths of light when excited, and their emissions can be fine-tuned by adjusting their size. By functionalizing QDs with cancer-specific ligands, antibodies, or peptides, they can target and image cancer cells from various types.
  • For instance, near-infrared QDs modified with cancer-selective peptides have demonstrated selective accumulation in colon cancer cells, enhancing imaging accuracy and sensitivity.
• QDs are conjugated with antibodies targeting cancer-specific proteins. When these QD-antibody complexes bind to a biomarker, they emit a detectable fluorescent signal. This allows for visualization of cancerous cells even when present in low numbers.

NANOPARTICLES

• The interfacial layer is an integral part of nanoscale matter, fundamentally affecting all of its properties (consists of ions, inorganic and organic molecules). 
• Nanoparticles can be engineered and designed to package and transport drugs directly where they’re needed. This results in the drugs causing the most harm to the particular or intended area of the tumour. 
  • This minimizes collateral damage to surrounding healthy tissues. 

• Along with carrying drugs, nanoparticles can carry specific compounds that will let them bind to molecules on tumour cells, allowing them to safely deliver the drug to the tumour site. Nanoparticles have a vast range of compositions, depending on the use or the product.

There are three major physical properties of nanoparticles

• Highly mobile in the free state.
• Enormous specific surface areas.
• Exhibit what is known as quantum effects.  

DIFFERENT TYPES OF NANOPARTICLES:

Nanoparticles can be classified into different types according to the size, morphology, physical and chemical properties. 

• Polymeric nanoparticles are organic-based nanoparticles. The active compounds are confined and surrounded by a polymer shell.
• Lipid nanoparticles consist of a solid core made of lipid and a matrix containing soluble lipophilic molecules. The external core of these nanoparticles is stabilized by surfactants and emulsifiers. 
• Carbon-based nanoparticles made of two main materials: carbon nanotubes and fullerenes.
• Ceramic nanoparticles are inorganic solids made up of oxides, carbides, carbonates and phosphates.
• Metal nanoparticles are prepared from metal precursors. 
• Semiconductor nanoparticles have properties like those of metals and non-metals 
• Gold nanoparticles are nanoparticles capped with citrate, tannic acid, or PVP capping agents with a gold composite core.
• Quantum dots are made with classical emerged carbon, silicon, gold and other types of nanomaterials

DIFFERENT WAYS NANOPARTICLES CAN WORK

Nanoparticles can kill cancer cells in many different ways, depending on which compounds are used. There are four major types.

• Heat particles - Some nanoparticles have a chemical reaction when exposed to heat, damaging the cancer cell it binds itself to.
• Magnetic Particles - An external magnetic field is applied, making the nanoparticles spin. When bound to cancer cells, the spinning mechanically destroys the cell membranes.
• Light Particles can be excited by ultra low power laser light at near-infrared wavelengths considered safe for the human body. These nanoparticles attach to specific components of cells to serve in an advanced imaging system to light up even single cancer cells.
• Chemical Particles have a chemical reaction when they meet the disease cell, due to its chemical compound. The chemical reaction is severe enough to destroy the cancer cell, but not strong enough to destroy healthy cells.

 

LUNG CANCER

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Lung cancer is a type of cancer that originates in the lungs, the organs responsible for taking in oxygen and expelling carbon dioxide during breathing. It occurs when cells in the lung grow uncontrollably, forming a mass or tumor that can interfere with normal lung function. These abnormal cells can invade nearby tissues and may spread (metastasize) to other parts of the body, such as the brain, liver, or bones.

This disease is primarily caused by long-term exposure to harmful substances, with smoking being the leading risk factor. Tobacco smoke contains carcinogenic chemicals that damage the lung's cells over time. However, lung cancer can also occur in non-smokers due to genetic predisposition, exposure to radon gas, air pollution, or secondhand smoke. 

There are two main types of lung cancer: non-small cell lung cancer (NSCLC), which is more common, and small cell lung cancer (SCLC), which is less common but more aggressive.

SYMPTOMS:

• A cough that persists or worsens over time, or coughing up blood or phlegm
• Pain in the chest that worsens when coughing, laughing, or breathing deeply
• Difficulty breathing
• Wheezing: A high-pitched sound caused by narrowed airways
• Fatigue
• Unexplained weight loss
• Hoarseness
• Swollen lymph nodes in the neck or above the collarbone
• Headaches (may be a symptom of paraneoplastic syndrome)
• Bone pain (may be a symptom of paraneoplastic syndrome)
• Swelling in the neck or face
• Loss of appetite
• Frequent lung infections like bronchitis or pneumonia

HOW DOES IT RELATE TO THE RESPIRATORY SYSTEM?

Lung cancer severely impacts the respiratory system by disrupting the normal function of key structures such as the bronchi, bronchioles, and alveoli. The disease often begins in the bronchi, the large airways that carry oxygen into the lungs, where tumors can grow and obstruct airflow, leading to persistent coughing, wheezing, and shortness of breath. As cancer progresses, it spreads to the bronchioles and alveoli, the tiny air sacs responsible for gas exchange. When these alveoli are damaged or filled with cancerous cells, the lungs struggle to supply oxygen to the bloodstream, causing fatigue and difficulty breathing.

Additionally, lung cancer can trigger excessive mucus production, inflammation, and pleural effusion (fluid buildup around the lungs), further restricting lung expansion and reducing oxygen intake. These complications make it harder for patients to breathe comfortably and contribute to the overall decline in respiratory function. Over time, the body becomes deprived of oxygen, leading to systemic effects such as dizziness, weakness, and organ strain. Without effective treatment, lung cancer can significantly compromise a person's ability to perform even basic activities, ultimately impacting their quality of life.

THE COST

Nanomedicine applications in lung cancer are still under research and development, with limited treatments currently available in clinical practice. As a result, specific cost data for nanomedicine-based lung cancer therapies are scarce.

General Costs of Nanomedicine Treatments:

• Doxil (PEGylated Liposomal Doxorubicin): This nanomedicine formulation of doxorubicin is priced at approximately $873 for a 20 mg vial, compared to about $50 for a 200 mg vial of conventional doxorubicin.
• Abraxane (Albumin-Bound Paclitaxel): The average cost per dose of Abraxane is around $5,054, whereas traditional paclitaxel ranges from $90 to $454 per dose.

Some argue that the higher cost of Nanomedicines is justified because patients who received Nanomedicines experienced less toxic side effects versus those who received the “free” anticancer drugs. For example, Cardiotoxicity is a well-documented side effect of Doxorubicin, which was seen much less in patients who took Doxil. Although Doxorubicin is less expensive by a great deal, more patients treated with Doxorubicin experience damage to the heart compared to Doxil-treated patients

This makes it unaffordable for most people (since about 75% of the world lives in developing and underdeveloped countries).

CANCER & TUMORS

WHAT IS IT?

Cancer is a disease in which some of the body’s cells grow uncontrollably and continue to spread to other regions in the body; it may start almost anywhere in the body. 

HOW DOES IT WORK/HOW IT SPREADS?

Normally, human cells grow and multiply through a process called cell division, forming new cells as needed. When cells grow old or become damaged, they die, and new cells take their place. However, this orderly process can sometimes break down, causing abnormal or damaged cells to grow and multiply uncontrollably. These cells may form tumors, which can be benign (non-cancerous) or malignant (cancerous).

Cancerous tumors have the ability to invade nearby tissues and spread to other parts of the body in a process called metastasis. This is when cancer cells break away from the original tumor and travel through the bloodstream or lymphatic system to form new tumors in distant organs. Metastatic cancer is the leading cause of cancer-related deaths, as it severely disrupts the body's functions. While treatment may help extend a person's lifespan or relieve symptoms, the primary goal is often to control the growth of the cancer and manage its effects on the body.

COMBATING METASTASIS:

Angiogenesis is a crucial and intricate process involving the creation of new blood vessels from existing ones. This process is essential for tumor growth, invasion, and metastasis. As tumors grow, they require additional blood supply for oxygen and nutrients, which is provided by angiogenesis. This process is tightly regulated by a balance of factors that promote and inhibit blood vessel formation.

The angiogenesis process and treatment of tumors via nanoparticle delivery. (a) Angiogenesis; (b) Drug delivery through NPs; (c) Tumor reduction.

 

NANOPARTICLES FOR LUNG CANCER

Several types of nanoparticles are being used or investigated for lung cancer therapy, including the following:

1. Organic Nanoparticles:

   • Liposomes: Cholesterol and phospholipid-based NPs, such as Lipoplatin, a liposomal formulation of cisplatin
   • Solid lipid nanoparticles and nanostructured lipid carriers.
   • Polymeric nanoparticles: Composed of materials like sodium alginate, chitosan, gelatin, polycaprolactone, polylactide, and polylactic acid.
   • Polymeric micelles: Colloidal NPs made of amphiphilic block copolymers
   • Dendrimers: Highly branched, symmetrical, radiating NPs

2. Inorganic Nanoparticles:

   • Mesoporous silica nanoparticles (MSNs): Used for drug and siRNA delivery
   • Magnetic nanoparticles (MNPs)
   • Metal nanoparticles (MeNPs): Including gold nanoparticles
   • Quantum dots (QDs)

3. Other Nanoparticle Types:

   • Virus nanoparticles

   • Carbon nanotubes
   • Metal-organic frameworks (MOFs)

1. Lipid-Based Nanoparticles: 

These include liposomes and solid lipid nanoparticles, which are biocompatible carriers capable of encapsulating both hydrophilic and hydrophobic drugs. Their lipid composition allows for efficient drug delivery and controlled release. An example is Lipoplatin, a liposomal formulation of cisplatin designed to reduce toxicity and improve targeting of cancer cells

2. Polymer-Based Nanoparticles: 

Constructed from biodegradable polymers, these nanoparticles offer controlled drug release and protection of therapeutic agents from degradation. They can be engineered to respond to specific stimuli within the tumor microenvironment, enhancing targeted delivery. 

3. Magnetic Nanoparticles: 

Composed of magnetic materials like iron oxide, these nanoparticles can be guided to tumor sites using external magnetic fields. They also serve as contrast agents in magnetic resonance imaging (MRI), aiding in both diagnosis and therapy. 

4. Gold Nanoparticles: 

Known for their unique optical and electronic properties, gold nanoparticles can be used for photothermal therapy, where they convert light into heat to destroy cancer cells. They can also enhance the effects of radiation therapy.

 

INHALABLE NANOMEDICINE FOR LUNG CANCER

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Inhalable nanomedicine is an innovative approach to treating lung cancer by delivering therapeutic agents directly to the lungs using nanoparticles. This method enhances drug delivery efficiency and minimizes systemic side effects.

HOW DOES IT WORK?

1. Formulation of Nanoparticles:

   • Therapeutic agents, such as chemotherapy drugs, are encapsulated within or attached to nanoparticles.
   • These nanoparticles are engineered to have specific properties, such as size, surface charge, and hydrophobicity, to optimize their delivery and effectiveness.

2. Inhalation Delivery:

   • The nanoparticle formulation is converted into an aerosol, which patients inhale using devices like nebulizers or inhalers.
   • Upon inhalation, the aerosolized nanoparticles travel through the respiratory tract.

3. Deposition in the Lungs:

   • The design of the nanoparticles allows them to deposit efficiently in the lung tissues, particularly targeting cancerous cells.
   • Factors such as particle size and breathing patterns influence the deposition efficiency.

4. Drug Release and Action:

   • Once deposited, the nanoparticles release the encapsulated drug in a controlled manner.
   • This targeted release increases the drug concentration at the tumor site while reducing exposure to healthy tissues.

Since nanomedicine is still an emerging field for lung cancer, there are limited datasets such as clinical trials available at the moment. However, below are two clinical trials that highlight the effects of integrating nanomedicine into lung cancer treatments.

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STUDY 1: 

Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial

A Phase III clinical trial was conducted to compare the effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined with carboplatin versus the conventional solvent-based paclitaxel with carboplatin in patients with advanced non-small cell lung cancer (NSCLC). The trial aimed to determine whether the nanoparticle-based treatment could improve patient outcomes. The results showed that the overall response rate (ORR) was higher in the nab-paclitaxel group (33%) compared to the solvent-based paclitaxel group (25%), indicating that patients who received nanomedicine had a better chance of their tumors shrinking.

Despite the improved response rate, the trial also found that patients receiving nab-paclitaxel experienced more cases of peripheral neuropathy (nerve damage that causes pain or weakness). However, this side effect was generally manageable and reversible, meaning that doctors could help patients control it, and it often improved over time. This suggests that while nab-paclitaxel has strong potential as a treatment option, managing side effects is still an important factor in its use.

Overall, this study supports the use of nanomedicine in lung cancer treatment by showing that nab-paclitaxel can improve effectiveness compared to traditional chemotherapy. Since this treatment resulted in higher response rates with manageable side effects, it provides a promising alternative to standard chemotherapy for patients with advanced NSCLC. This research highlights how nanomedicine can help refine existing treatments and improve patient outcomes in lung cancer care.

 

STUDY 2:

Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC

Another Phase III clinical trial evaluated whether nab-paclitaxel was as effective as docetaxel in patients with advanced NSCLC who had already undergone previous treatments. The study was designed to test whether nab-paclitaxel was "non-inferior" (meaning it was at least as good as docetaxel in treating lung cancer). The trial found that nab-paclitaxel was just as effective as docetaxel in terms of overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). This means that both treatments allowed patients to live for similar lengths of time and had comparable success in controlling cancer growth.

One key finding of the study was that nab-paclitaxel had a better safety profile than docetaxel. Patients who received docetaxel often experienced severe side effects, such as neutropenia (a dangerous drop in white blood cells) and febrile neutropenia (a condition where low white blood cells cause fever and infections). In contrast, nab-paclitaxel caused fewer of these serious side effects, making it a safer and potentially more tolerable treatment option for patients who had already been through chemotherapy.

This study is significant because it suggests that nanomedicine-based treatments may be a better option for lung cancer patients who need a second-line therapy (treatment given after the first one stops working). Since nab-paclitaxel was as effective as docetaxel but had fewer severe side effects, it could provide a better quality of life for patients while still offering strong cancer-fighting benefits.

 

Nanomedicine presents a revolutionary approach to lung cancer treatment, offering improved precision, targeted drug delivery, and reduced side effects compared to conventional therapies. Through the use of nanoparticles, treatment efficacy is significantly enhanced by allowing for direct drug transport to cancerous tissues while sparing healthy cells. This minimizes toxicity and improves patient outcomes. Furthermore, nanotechnology has the potential to advance early detection methods, ensuring that lung cancer can be identified at more treatable stages, ultimately increasing survival rates and reducing recurrence.

Despite its promising benefits, the implementation of nanomedicine comes with challenges that must be addressed. Concerns surrounding long-term toxicity, immune responses, and potential environmental impacts require extensive research and regulation. The high cost of nanomedicine also raises ethical concerns regarding accessibility, as cutting-edge treatments must be made available to a broader population rather than remaining exclusive to wealthier nations or individuals. Overcoming these barriers is crucial for the widespread adoption of nanomedicine in the medical realm. 

In conclusion, as research continues, nanomedicine is likely to transform the future of lung cancer treatment. Moreover, the potential of nanomedicine extends beyond lung cancer, holding promise for treating other diseases with high precision and effectiveness. While challenges remain, the continued development of nanotechnology in medicine may pave the way for a new era in cancer treatment, improving patient survival rates and overall quality of life.

 

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I am incredibly grateful to the Calgary Youth Science Fair for providing me with the opportunity to participate in such an exciting and enriching experience. The support and guidance I have received from my friends, family, and teachers have been invaluable throughout this journey, and I truly appreciate their encouragement. A special thank you to my science fair director for their constant feedback, dedication, and for keeping us on track every step of the way. This experience has been both inspiring and educational, and I am so thankful to have been a part of it!