Nanoparticles (NPs) are emerging as effective tools for targeted cancer therapy, addressing the shortcomings of conventional chemotherapy. Their ability to achieve enhanced permeability and retention, alongside modifications for active targeting of cancer cell markers, improves drug delivery efficacy and minimizes damage to healthy cells. NPs also offer strategies to overcome drug resistance by bypassing efflux pumps and delivering gene-silencing materials.

1. NANOPARTICLES IN CANCER TREATMENT
Manisha lohan
Msc biotechnology 2nd year
Roll no . 201636
Department of Biotechnology
Central university of Haryana

2. CANCER THERAPIES
• treatments for cancer is a major problem across the world.
• Chemotherapy is a conventional and widely used cancer treatment method. It indiscriminately killing vigorously growing cells, including tumor and
normal cells, some serious side effects including bone marrow suppression, hair loss, and gastrointestinal reactions.
• most of the cytotoxic drugs are insoluble in water, which necessitates the inclusion of the cosolvents ,the co-solvents such as Cremophor EL and
polysorbate 80 also can cause sideeffects .
• Therefore, developing drugs that more accurately target tumor cells, instead of normal cells, has been the purpose of a large proportion of cancer-
related research in the past few decades.
• still many unavoidable adverse effects, and the development of drug resistance has always been a problem.
https://www.dreamstime.com/stock-illustration-cancer-chemotheraphy-diagram-showing-accurately-progression-how-halted-using-
chemotherapy-image43334620

3. NPs IN CANCER THERAPY
• NPs with a diameter range of 10 to 100 nm are generally considered suitable for
cancer therapy, as they can effectively deliver drugs and achieve enhanced
permeability and retention (EPR) effect.
• Smaller particles can easily leak from the normal vasculature (less than 1–2 nm)
• particles that are larger than 100 nm will be cleared from circulation by phagocytes.
• the surface characteristics of NPs can influence their bioavailability and half-life.
• NPs that are coated with hydrophilic materials such as polyethylene glycol (PEG)
lessen the opsonization and therefore avoid clearance by the immune system.
• which increases the time period of drugs in circulation.
o Specific drug delivery
o prevent degradation of drugs
o slow release of drug
o overcome drug resistance
o Increase solubility of drug
o don’t target other cells etc
Frontiers | Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance |
Molecular Biosciences (frontiersin.org)

4. Liposomes
https://www.researchgate.net/figure/Comparison-of-PEGylated-liposome-with-conventional-liposome-PEGylated-liposome-
high_fig3_336002500
o Liposomes are good vehicles for drug delivery
o biocompatibility,
o Stability
o biodegradability
o protect the encapsulated drug from degradation,
o decrease nonspecific toxicity of the drug
o Faciliate target specific delivery.
o hydrophilic drug ,hydrophobic drug can be delivered .
PEGylated liposomes
imparting longer circulation times
in weak activation of complement system.
PEGylation of liposomes escape the phagocytosis.
Liposomes are phospholipid bilayer self-assemblies with a vesicle size range of 50–1000 nm
Polyethylene glycol (PEG) is a neutral, biocompatible polymer with low toxicity
and solubility in organic and aqueous solutions, which makes it a popular choice
to shield hydrophilic molecule and solubilize hydrophobic molecule.

5. MECHANISMS OF TARGETING
• Targeting of cancer cells specifically is a vital characteristic of nano-carriers for drug delivery, as it enhances the
therapeutic efficacy while protecting normal cells from cytotoxicity.
• The targeting mechanisms can be broadly divided into two categories, passive targeting and active targeting.
Frontiers | Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming
Drug Resistance | Molecular Biosciences (frontiersin.org)

6. Active targeting
• direct interactions between ligands and receptors.
• The ligands on the surface of NPs are selected to target the molecules that
are overexpressed on the surface of cancer cells, which allows them to
distinguish targeted cells from healthy cells.
• After binding receptor-mediated endocytosis, which internalized NPs to
release drugs.
• suitable for macromolecular drug delivery, such as proteins and siRNAs.
• The types of targeting moieties include monoclonal antibodies, peptides,
amino acids, vitamins, and carbohydrates .
• Cancer cell markers , include transferrin receptor, folate receptor,
glycoproteins, and the epidermal growth factor receptor (EGFR) etc.

7. Targeting Cancer Cells
Targeting cancer cell-surface Transferrin receptors
Transferrin
serum glycoprotein,
functions to transport
iron into cells.
Transferrin receptors are overexpressed in most
solid tumor cells due to the increased requirement
of iron and are expressed at low levels in normal
cells.
transferrin-conjugated NPs [liposomes] are used as
an active targeting method to deliver drugs for
cancer treatment .
higher cellular uptake efficiency and enhanced
intracellular delivery of drugs.
Transferrin
https://www.researchgate.net/publication/326077312

8. Targeting cancer cell-surface folate receptor
Folate
vitamin, is essential in nucleotide synthesis.
Folate targeting offers several advantages because
folic acid is small, inexpensive, stable over a broad
range of temperatures and pH values, and non-
immunogenic could bypass multidrug efflux pumps.
It is internalized by a folate receptor
alpha isoform of folate receptor (FR-α) is
overexpressed in approximately 40% of human
cancers,
folate-conjugated nanomaterials has been widely
used for cancer treatments,like liposomes,
Folate

9. Targeting cancer cell-surface carbohydrates
direct lectin targeting pathway,
Targeting cancer cell-surface carbohydrates by
lectins conjugated to NPs.
Example Carbohydrate antigen 50 (CA50) is
cancer-specific antigen expressed on the surface
of human colorectal Colo-205 cancer cells.
reverse lectin targeting pathway
targeting lectins on cancer cells using
carbohydrates moieties onto NPs.
level of cell surface lectins is high in tumor cells .
https://pubmed.ncbi.nlm.nih.gov/3072905/
https://healthjade.com/what-is-lectin/

10. Epidermal growth factor receptor is a member of the ErbB family of tyrosine
kinase receptors.
Targeting Epidermal growth factor receptor on cancer cells .
EGFR and HER-2, are known to mediate a cell signaling pathway for growth and
proliferation in response to the binding of the growth factor ligand.
Mutations of EGFR leading to over-expression or over-activity of EGFR cause
cancers like lung cancer ,colorectal cancer , and glioblastomas .
Some monoclonal antibodies targeting EGFR including Cetuximab, ABX-EGF and
EMD-7200.
The antibody can be modified in the surface or entrapped inside the
nanoparticles for active targeting of EGFR.
Targeting EGFR, which is overexpressed in varieties of cancers
EGFR
https://ars.els-cdn.com/content/image/1-s2.0-S177322472031217X-fx1_lrg.jpg
cetuximab (Cmab) was conjugated to temozolomide (TMZ)
loaded poly(lactic-co-glycolic acid) NPs (PLGA-NPs), termed
as (Cmab-TMZ-PLGA-NPs)

11. Targeting Endothelium
NPs do not directly target cancer cells but instead have an effect on
angiogenesis, which is another method of cancer treatment.
The interaction between
VEGF and VEGFRs plays an
essential role in
vascularization.
This signalling is important
for cancer cell invasion.
The VEGFR2 expression is up-regulated in the tumor endothelium cells .
various approaches to interfere with the VEGF-VEGFR interaction and its
signaling, for example by use of tyrosine kinase inhibitors, antibodies
against VEGFR, small interfering RNA (siRNA).

12. drugs (Paclitaxel and Doxorubicin) with liposomes can be used.
In one study, Demirovic et al. generated a antibody recognizing VEGFR-2. This antibody was attached to liposomes that were used for targeting VEGFR2 expressing
human cancer cells in culture.
https://www.researchgate.net/figure/Nanomedicine-
used-in-cancer-immunotherapy-Nanoparticles-could-be-
functionized-to_fig8_326077312

13. MECHANISMS OF NPS IN OVERCOMING DRUG RESISTANCE
Efflux transporters pump the drug out of the cell, leading
to a failure of treatment.
P-glycoprotein (P-gp), one of the most widely
investigated efflux transporters, is overexpressed in
several drug resistant tumors.
NPs largely enter the cell through endocytosis instead of
diffusion and release the drug at a perinuclear site
within the cell, away from cell membranes and efflux
pumps.
Can design NPs that encapsulate both efflux pump
inhibitors and drugs .
nanoparticles deliver siRNAs or short hairpin RNA
(shRNA)- to silence drug resistant genes.
deliver P-gp efflux pump inhibitor with anticancer drugs
to achieve the highest resistance reversal effect.
at: https://www.researchgate.net/publication/326077312

14. TARGETING APOPTOTIC PATHWAY
https://ars.els-cdn.com/content/image/1-s2.0-
S1388198114001723-fx1_lrg.jpg
ceramide is able to restore the expression of wild-type p53 protein,
by modulating alternative pre-mRNA splicing.
NPs offers a more effective platform to deliver ceramide into cancer cells that carry p53 missense
mutations,
As p53 plays a significant role in apoptosis, reinstating p53 function considered a potential way to kill
cancer cells.
Transfecting the p53 gene by lipid NPs has been reported in lung cancer cells
https://www.researchgate.net/figure/Preparation-of-FL-ceramide-and-TR-ceramide-co-loaded-A-PLGA-liposome-hybrids-and-
B_fig1_257072151

15. REFRENCES
• file:///C:/Users/HP/Downloads/JDT-2019-RA-0367_Proof_hi.pdf
• Frontiers | Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in
Overcoming Drug Resistance | Molecular Biosciences (frontiersin.org)
• https://www.sciencedirect.com/science/article/pii/S2090123217300644
• https://www.sciencedirect.com/science/article/abs/pii/S177322472031217X
• https://www.researchgate.net/figure/Preparation-of-FL-ceramide-and-TR-ceramide-co-
loaded-A-PLGA-liposome-hybrids-and-B_fig1_257072151
• https://www.researchgate.net/figure/Nanomedicine-used-in-cancer-immunotherapy-
Nanoparticles-could-be-functionized-to_fig8_326077312
• https://healthjade.com/what-is-lectin/
• https://www.researchgate.net/figure/Comparison-of-PEGylated-liposome-with-
conventional-liposome-PEGylated-liposome-high_fig3_336002500
• https://www.nagwa.com/en/explainers/640142370207/