Nanoparticles Mediated Cancer Therapy


Treatment Approach Towards Cancer :

  1. Surgery
  2. Chemotherapy
  3. Radiation Therapy
  4. Immuno Therapy
  5. Targeted Therapy
  6. Hormone Therapy
  7. Stem Cell Transplantation
  8. Precision Medicine

Side Effects of Above Treatment Approaches:

  1. Nausea and vomiting
  2. Fatigue
  3. Hair Loss
  4. Mouth Sores
  5. Changes in Appetite
  6. Auto Immune Reactions
  7. Digestive System Issues
  8. Pneumonitis (Inflammation of the Lungs)

New Treatment Approach :-

What is Nanoparticles ?

Nanoparticles can be designed to carry therapeutic drugs, genes, or other molecules to specific targets within the body.
Nanoparticles can be loaded with imaging agents to enhance contrast in various imaging modalities, such as MRI, CT, and fluorescence imaging.
These imaging nanoparticles can help visualize specific cells, tissues, or biological processes within the body.
Nanoparticles can interact with biological molecules, including proteins, nucleic acids, and lipids.
In cancer treatment, nanoparticles can be used for targeted drug delivery, allowing for the selective delivery of therapeutic agents to cancer cells while sparing healthy tissues.
Nanoparticles may also be employed in photothermal therapy or photodynamic therapy for cancer treatment.

Types of Nanoparticles :

  1. Liposomes
  2. Polymeric Nanoparticles
  3. Gold Nanoparticles
  4. Iron Oxide Nanoparticles
  5. Silica Nanoparticles
  6. Quantum Dots
  7. Carbon Nanotubes
  8. Dendrimers
  9. Polymeric Micells
  10. Nanogels
  11. Magnetic Nanopaarticles
  12. Protein-Based Nanoparticles
  13. Nanocapsule
  14. Upconversion Nanoparticles
  15. Hybrid Nanoparticles
  16. Lanthanide Nanoparticles
  17. RNA Nanoparticles

Synthesis of Nanoparticles:

  1. Bottom-Up Approach: This process is also referred to as the constructive method because it builds materials from simpler substances, such as atoms, clusters, and NPs. Some of the processes that are frequently employed in this process include spinning, solgel synthesis, chemical vapor deposition (CVD), plasma or flame spraying synthesis, laser pyrolysis, and biosynthesis.
  2. Top-Down Approach: A larger molecule is broken down or decomposed into smaller units that are converted into NPs. It includes techniques like mechanical milling, nanolithography, chemical etching, laser ablation, sputtering, electro-explosion, and thermal decomposition. It is also known as the destructive method, which reduces bulk material or substance to synthesis NPs.

Mechanisms of Nanoparticle-Mediated Cancer Therapy:

  1. The capacity to stay stable in the vascular system (blood) until they reach their target, TME (Tumor Microenvironment)
  2. The ability to evade the clearance of the reticuloendothelial system (RES)
  3. The ability to escape the mononuclear phagocyte system (MPS).
  4. Accumulate in the tumor microenvironment (TME) through the tumor vasculature
  5. Penetrate the tumor fluid at high pressure
  6. Only interact with tumor cells once they reach the target
  1. Active Targeting
  2. Passive Targeting

Active Targeting:

  1. Surface Modifications: Nanoparticles are functionalized with ligands, antibodies, or peptides that have a high affinity for specific receptors or antigens on the surface of cancer cells. The specific characteristics of the tumor microenvironment are that the receptors on cancer cells are overexpressed and that overexpressed receptors are targeted by the nanoparticles.
  2. Receptor-Mediated Endocytosis: Active targeting facilitates the binding of nanoparticles to specific receptors on the cancer cell surface, triggering receptor-mediated endocytosis. Once NPs get into the cell microenvironment, the therapeutic payload can be released within the cancer cell, enhancing the drug’s intracellular concentration
  3. Specificity to Tumor Heterogeneity: Active targeting helps address the heterogeneity of tumors by aiming at specific receptors that may vary among different cancer subtypes or individual patients. This approach supports personalized medicine by giving treatments to the unique molecular characteristics of each patient’s cancer.
  4. Examples of Active Targeting Strategies:
    • Antibody-Conjugated Nanoparticles: Monoclonal antibodies targeting specific cancer cell receptors are conjugated to the nanoparticle surface.
    • Peptide-Targeted Nanoparticles: Short peptides with affinity for cancer-specific receptors are used for active targeting.
    • Aptamer-Functionalized Nanoparticle: Aptamers, which are short, single-stranded DNA or RNA molecules, can be selected to bind specificially to cancer cell targets.

Passive Targeting:

  1. Enhanced Permeability and Retention (EPR) Effect:
    • Tumors often have abnormal blood vessels with increased permeability, allowing nanoparticles to leak into the tumor interstitium. The impaired lymphatic drainage in tumors contributes to the retention of nanoparticles in the tumor tissue.
  2. Nanoparticle Characteristics for Passive Targeting:
    • Nanoparticles with sizes ranging from 10 to 200 nanometers are optimal for passive targeting, as they can pass through leaky vasculature while avoiding rapid clearance. When compared to irregularly shaped particles, spherical or rod-shaped nanoparticles may show better circulation times and greater accumulation.
  3. Prolonged Blood Circulation:
    • Surface modifications with polymers like polyethylene glycol (PEG) create a stealth effect, reducing recognition by the immune system and extending circulation time. By this way NPs get extra time in circulation, which in turn increases the probability of passive accumulation.
  4. Size-Dependent Permeation:
    • The EPR effect is size-dependent; the smaller the nanoparticles, the greater the diffusing power through the tumor vasculature and accumulation in the tumor. Once NPs enter the tumor microenvironment, they can penetrate the interstitial space.
  5. Tumor Microenvironment Factors:
    • The hypoxic (lower oxygen) nature of tumors can contribute to the EPR effect, influencing vascular permeability and the retention of nanoparticles. The composition of the tumor extracellular matrix influences nanoparticle penetration and distribution within the tumor.
  6. Selective Accumulation in Tumors:
    • Passive targeting minimizes uptake by healthy tissues, as the EPR effect is more pronounced in tumors.
    • Nanoparticles tend to accumulate selectively in tumor tissues due to the combination of leaky vasculature and impaired lymphatic drainage.
  7. Applications of Passive Targeting:
    • Chemotherapy: Passive targeting is commonly employed in the delivery of chemotherapeutic agents to tumors.
    • Imaging Agents: Contrast agents for imaging modalities, such as magnetic resonance imaging (MRI) and computed tomography (CT), can also utilize passive targeting.

Mechanisms of NPs in Overcoming Drug Resistance:

  1. Increased Drug Delivery:
    • Nanoparticles, especially those designed for passive or active targeting, can accumulate more efficiently in tumor tissues, including drug-resistant cancer cells.
  2. Intracellular Drug Release:
    • Controlled-release formulations can be engineered to release drugs gradually, optimizing drug exposure to cancer cells over an extended period.
    • Some nanoparticles facilitates the escape of drugs from endosomes, enhancing their delivery to the cytoplasm and improving efficacy against resistant cells.
  3. Active Targeting of Drug-Resistant Cells
  4. Combination Therapy:
    • Nanoparticles can carry multiple therapeutic agents, combining drugs with different mechanism of action.
  5. Avoiding Efflux Pump Recognition:
    • The surface of nanoparticles can be modified to evade recognition by efflux pumps, reducing the likelihood of drug expulsion.
    • Nanoparticles can improve drug retention within cells, counteracting the rapid expulsion mediated by efflux pumps.
  6. Penetrating Tumor Microenvironment:
    • Nanoparticles with appropriate sizes and surface properties can penetrate deep into the tumor, reaching drug-resistant regions.
  7. Cancer Stem Cell Targeting:
    • Nanoparticles can be engineered to specifically target cancer stem cells, which are often associated with drug resistance and tumor recurrence.

Advantage of NPs in Cancer Therapy:

  1. Targeted Drug Delivery
  2. Enhanced Drug Accumulations in Tumors
  3. Reduced Systemic Toxicity:
    • Targeted drug delivery minimizes the exposure of healthy tissues to cytotoxic agents, reducing the side effects and systemic toxicity associated with traditional chemotherapy.
  4. Combination Therapies
  5. Imaging and Diagnostic
  6. Overcoming Drug Resistance
  7. Minimized Off-Target Effects:
    • The targeted nature of nanoparticles minimizes off-target effects on healthy tissues, leading to a more favorable therapeutic index.

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