Emerging Nanocarrier-Based Drug Delivery in Cancer Therapy

Cancer ranks among the top causes of mortality globally, trailing only cardiovascular diseases. Chemotherapy is essential in targeting concealed cancer micro-foci and circulating cancer cells. It operates by employing chemical agents to eliminate or inhibit the proliferation of cancer cells. Since cancer cells typically proliferate at a much quicker rate than normal cells, chemotherapy mainly focuses on these rapidly dividing cells. Unfortunately, it also impacts healthy cells that grow quickly, resulting in various side effects. Numerous factors heighten the risk of certain cancers, such as lung, breast, and ovarian cancers. These factors include obesity (associated with increased risks for kidney, uterus, and bowel cancers), family history, depression, and exposure to environmental toxins. Some prevalent cancers affecting humans are prostate, lung, stomach, breast, bowel, ovarian, liver, kidney, head and neck, thyroid, and brain cancers. The World Health Organization (WHO) estimates that by 2030, there will be approximately 13.1 million deaths due to cancer. While conventional cancer treatments remain commonly used, they frequently harm healthy tissues and result in significant side effects. This occurs because traditional medications possess low specificity, poor solubility in water, limited bioavailability, and diminished therapeutic effectiveness. When administered at higher doses, they may even lead to toxic reactions. In this scenario, nanotechnology has emerged as a significant approach to enhance cancer therapy.

The choice of a suitable nanocarrier depends on strategies used to distinguish cancer cells from normal cells. Smart Drug Delivery Systems (SDDS) make use of the differences between healthy and cancerous tissues. Two major approaches exist:

1. Passive targeting: Relies on the Enhanced Permeability and Retention (EPR) effect to accumulate drugs in tumor tissues.
2. Active targeting: Uses specific receptors over-expressed on cancer cells to deliver drugs directly, like a guided missile.

After identifying the target site, nanocarriers are capable of releasing drugs in controlled amounts. Depending on their design, the release of drugs can be activated by internal factors (such as pH, enzymes, or temperature) or external triggers (like light, ultrasound, or magnetic fields). Targeted therapies are specifically designed to disrupt abnormal signaling pathways in cancer, including overactive receptors, growth factors, or mutated proteins. These therapies aim to inhibit tumor growth, trigger apoptosis, enhance the immune response, or improve the focused delivery of chemotherapy agents. The primary objective is to minimize side effects on healthy tissues while maximizing treatment efficacy. Conventional chemotherapy drugs impact both healthy and cancerous cells, resulting in a non-specific distribution across the body. This leads to a decrease in the drug dose reaching the tumor and increases systemic toxicity, which often leads to suboptimal outcomes.

1. Selecting the best medication ,
2. Identifying the appropriate treatment target, and
3. Accurately delivering the medication to the diseased spot.

These issues can be resolved with the use of nanocarriers. These are nanoscale colloidal systems that carry genes, enzymes, or tiny chemicals that fight cancer. Nanocarriers can increase local medication concentrations while preventing drug degradation and lowering renal clearance by avoiding healthy tissues and building up in malignancies. Additionally, they increase solubility, regulate release, and prolong medication half-life, all of which improve therapeutic results. Because of their normal size range of 10–400 nm, nanocarriers are appropriate for medication delivery. Because of their small size, they can transport a lot of medication, stay in the bloodstream longer (particularly when PEGylated), and use the EPR effect to target tumor areas specifically. They can also assist in overcoming the drawbacks of traditional chemotherapy, including multidrug resistance (MDR), low absorption, and poor solubility.MDR is often caused by drug-efflux transporters like P-glycoprotein, which are overexpressed in cancer cells. The use of siRNA-loaded nanocarriers has shown promise in blocking drug resistance by preventing renal clearance and degradation, thereby improving blood circulation time. Studies have demonstrated that combining siRNA with chemotherapy can sensitize resistant cancer cells and improve treatment effectiveness. Delivering both siRNA and chemotherapy drugs in the same nanocarrier system is considered a more efficient approach to overcoming multidrug resistance.

Nanocarriers (NCs) used in Cancer Drug Delivery

Several innovative strategies are being used in cancer therapy, and many of these involve nanocarriers (NCs) made from organic or inorganic particles, as well as synthetic lipids, proteins, and polymers. Delivering drugs through NCs offers several benefits compared to directly administering chemotherapeutic drugs. These advantages include:

1. Improved drug delivery efficiency 
2. Protection of drugs from degradation in the bloodstream
3. Targeted delivery to tumor sites
4. Reduced systemic toxicity
5. Better solubility of drugs

Enhanced Pharmacological Properties (Pharmacodynamics and Pharmacokinetics)

Nanoparticles (NPs), typically 1–100 nm in size, have a high surface area-to-volume ratio, which gives them unique biological activities. This permits them to bind, absorb, and transport therapeutic substances such as medicines, DNA, RNA, proteins, and imaging molecules. The efficiency of NCs depends mostly on their size, shape, and surface qualities. Numerous NC kinds with various surface properties and architectures have been created over time.

Conventional NCs do have several drawbacks, though. They frequently exhibit decreased permeability, poor retention, drug resistance, increased toxicity, instability, and lack of biocompatibility. These problems occur as a result of circulation difficulties or aberrant vascular networks within the tumor microenvironment. In contrast, targeted and stimuli-responsive NCs overcome these problems. They are more precise, stable, biocompatible, and show enhanced permeability and retention (EPR) effects at tumor sites. This means they can release drugs in response to biological signals, reduce side effects, and improve overall therapeutic efficacy.

INORGANIC NCs :-

Mesoporous silica nanocarriers (MSNCs) are widely used in cancer therapy because of their porous structure, large surface area, adjustable size, and good biocompatibility. Their pores can be modified to control how much drug they hold and how quickly it is released, ensuring that anticancer drugs are delivered at the right place and time without premature leakage. MSNCs can carry both hydrophilic and hydrophobic drugs, making them versatile carriers for different therapies. For example, they have been used to deliver doxorubicin (a water-soluble drug) together with JM15 (a water-insoluble drug). They can reach tumors through passive targeting (like the enhanced permeability and retention effect) or active targeting by attaching ligands such as hyaluronic acid, transferrin, or coatings with proteins, enzymes, or magnetic nanoparticles. By tuning their size and surface properties, MSNCs can improve drug uptake, distribution, and overall effectiveness.

Gold nanocarriers (AuNCsGold nanocarriers (AuNCs) are advantageous in cancer therapy, especially photothermal therapy, due to their ability to efficiently convert light to heat. Effective use of AuNCs will largely depend on the size, shape, surface plasmonic properties, and surface chemistry of the nanoparticles. Size and shape of AuNCs are important in cellular uptake and targeting and releasing drugs to subsequent sites. Smaller sizes of AuNC travel deeper into tissues, whereas larger particles, those in the range of 100 to 200 nanometers, mainly travel at the surface level which can influence bioavailability and circulation times. The biocompatibility of AuNCs and ease of modification with certain surface coatings for enhanced drug carrier efficiency. By attaching anticancer drugs or antibody to the surface of AuNCs, they can be used to improve action of the drug and their tumor targeting. Examples of AuNCs that utilize pH-sensitive materials for drug release to specifically to tumor cells can take advantage of lower pH levels than human cells. AuNCs such as methotrexate-loaded AuNCs were utilized to target the folate receptor of breast cancer cells taken seriously and promoted death of cancer cells by changing gene expression.

Magnetic nanocarriers (MNCs) are also promising for cancer therapy. They can generate heat to treat tumors (hyperthermia) and deliver drugs directly to cancer cells, reducing side effects. Their performance depends on size, surface chemistry, and magnetic properties. Modifying their surface with hydrophilic molecules like PEG helps them avoid immune clearance and stay longer in the bloodstream, improving treatment effectiveness. Magnetic nanocarriers (MNCs) can be made more stable and biocompatible by attaching organic or inorganic compounds, which improves their effectiveness in cancer chemotherapy and gene therapy. Their special property is that they can be guided by external magnets, allowing targeted delivery to tumor tissues. They are also useful in diagnosis, especially in MRI, because they provide clear and detailed imaging. For example, magnetic iron oxide nanoparticles are commonly used for lung MRI due to their strong magnetization, safety, and ability to carry and release drugs. MNCs are safely usable to invade tumour(cancer) cells.  Similarly, PEI-conjugated iron oxide nanoparticles have been used for MRI-based cancer imaging.

Carbon nanotube nanocarriers (CNTs) are long, tube-like structures with unique physical, chemical, and biological properties, making them valuable for drug delivery. They have been used to carry anticancer drugs such as doxorubicin, paclitaxel, methotrexate, and even small interfering RNAs (siRNAs). Combining siRNA with chemotherapy offers strong potential in cancer treatment, but the main challenges include precise targeting, protecting the cargo, and ensuring release at the right site. CNTs are especially useful because they have a large surface area, strong adsorption ability, high durability, easy functionalization, and excellent uptake by cells. Their surfaces can also be modified through covalent or noncovalent bonding, making them a highly versatile nanomaterial.

LIPOSOMES NCs:-

Liposomes are very tiny spherical carriers made of an outer lipid layer and an inner core that can hold either water-loving (hydrophilic) or fat-loving (hydrophobic) drugs. They were the first nano-sized drug delivery systems approved for clinical use. By changing the structure of their lipid layer, liposomes can be designed for different purposes. For example, they can be modified to mimic the properties of natural cell membranes.

The inner water-based core of liposomes can also be filled with certain drugs using special techniques like the ammonium sulfate gradient method. However, regular liposomes are cleared quickly from the bloodstream because they are recognized by immune proteins and destroyed by macrophages. To solve this problem, surface-modified liposomes have been developed. These can be coated with molecules such as monoclonal antibodies, glycoproteins, carbohydrates, vitamins, or peptides to specifically target cancer cells. Researchers have also created "stealth liposomes" by coating them with PEG, a hydrophilic polymer. This coating helps the drugs stay in the blood longer and reduces their rapid elimination. Still, PEG-coated liposomes can sometimes lose reliability after injection, so newer PEG-dendron phospholipids have been developed to make “super-stealth” liposomes. Laboratory studies show that ligand-targeted liposomes can enter cancer cells more effectively, for example, by attaching to prostate-specific membrane antigens. After many years of research, liposomes are now a proven platform for delivering different anti-cancer drugs, such as docetaxel, as well as genetic materials like nucleic acids. They are already being used to treat cancers such as breast and prostate cancer, and several new liposome-based medicines are currently in clinical trials for cancer therapy.