Nanoparticles offer potential benefits for cancer treatment by improving drug solubility and targeting tumors. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are promising drug delivery vectors that can incorporate chemotherapy drugs and tune their release rates over days to months. Nanoparticles accumulate in tumors through enhanced permeability and retention, exploiting abnormal tumor blood vessels. Combining multiple anticancer agents in nanoparticles may allow more effective combination therapies by controlling drug ratios and pharmacokinetics with a single delivery system.

1. Nanotherapy for Cancer
LONE FAWAD MAJEED
DEPARTMENT OF NANOTECHNOLOGY,
UNIVERSITY OF KASHMIR.

3. History of Cancer Therapy

4. Cancer Biology and Rational Treatment Design.
• Cancer pathogenesis is a complex multistep process where cells attain
certain hallmark properties as a result of both genetic and epigenetic
alterations.
• Carcinogenesis is primarily a consequence of changes in the genetic
code or gene expression.

5. Hallmarks of Cancer

6. • Understanding cancer pathogenesis has allowed for development of
more effective therapies. For instance, cancer cells can receive
increased proliferative signaling by up-regulating surface growth
factor receptors such as EGFR.
• These discoveries have been translated into promising clinical
therapies in the form of EGFR specific inhibitors.
• Obstacles in Cancer Chemotherapy.
• Although our understanding of cancer pathogenesis is increasing, the
disease process remains extremely complex and much is still
unknown.

7. IMPROVING CANCER THERAPIES WITH NANOTHERAPIES
• Introduction to Nanotherapies.
• Nanotechnology offers the potential to improve drug solubility and
stability, prolong drug half-lives in plasma, minimize off target effects,
and concentrate drugs at a target site.
• Substantial past research effort has resulted in methods to
incorporate therapeutic agents into biocompatible nanodevices
including polymer nanoparticles, liposomes, micellar systems,
inorganic nanoparticles, nanotubes, and dendrimers.

8. Lists a few examples of nanoparticle therapeutics that are currently
approved by the FDA or in clinical trials.

9. Relative sizes of nanoparticles compared to common
biological structures.

10. Small Molecule Delivery.
• Folkman first described a method for incorporating proteins and
macromolecules into polymers in 1964.
• Many polymers are safe to use clinically, and the most extensively
studied are poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid)
(PLGA), which was first approved by the FDA.
• There are multiple PLA and PLGA delivery systems on the market
including Zoladex and Nutropin Depot.
• PLGA nanoparticles are being formulated to target specific tumors
and deliver a host of agents including chemotherapy drugs or RNAi.
• Upon exposure to physiologic solutions, PLGA undergoes hydrolysis
into biocompatible metabolites, glycolic acid (GA) and lactic acid (LA),
which are eventually metabolized through the citric acid cycle.

11. • Biodegradable, polymer nanoparticles provide several distinct
advantages as a drug delivery vectors ;
tunable payload release characteristics and;
superior pharmacokinetics.
The ratio of LA to GA subunits can be adjusted to tune the rate of
drug release, allowing for release profiles ranging from days to months.
• PLGA particles are particularly useful for agents that have low
solubility in water, and therefore are difficult to formulate as drugs.
• The majority of clinically available chemotherapeutic agents are
lipophilic, and have low solubility in water.
• PLGA has industrial production.

12. Introduction to Gene Delivery.
Gene therapy is the cellular delivery of nucleic
acids in order to modulate gene expression
toward treating disease.
The U.S. FDA approved its first clinical trial in
gene therapy in 1990.
Michael Blease conducted an ex vivo gene
therapy trial on two children with adenosine
deaminase deficiency, a form of severe
combined immunodeficiency (SCID).

13. Methods of Gene Delivery.
• There has been significant progress in the field, despite earlier setbacks,
including the death of 18 year-old Jesse Gelsinger in 1999,and the
development of T cell leukemia in multiple patients receiving gene
therapies for SCID.
• Nonviral vectors; liposomes; standard; toxicity issue; no industrial pro due
to unstability ; low transfection.
• Polycationicpolymers ; > transfection but >cytotoxicity.

16. Targeting Tumors with Nanoparticles.
• Nanoparticle systems also have unique properties that allow for both
passive and active targeting of tumors.
• Because of up regulation of proangiogenic signaling, most solid
tumors are hypervascular. However, the new vessels have abnormal
architecture and are highly permeable.
• Tumor has; poor lymphatic drainage thus allow accumulation of
40Kda molecules within.
• Nanoparticles exploit this feature, which is called the enhanced
permeability and retention (EPR) effect, to target solid tumors. The
ideal size range to benefit from the EPR effect is between 10 to 200
nm.

17. Schematic illustration of enhanced permeability and retention (EPR) effect of nanoparticles in tumors. The newborn tumor vessels usually have abnormal
architecture, and are lack of effective lymphatic drainage, thereby allowing macromolecules to be retained in the tumor. The tight vascular endothelial cells in the
normal vasculatures could form a barrier to prevent macromolecules from extravasation. Nanoparticles designed with a suitable size will selectively leak into
tumor tissue but spare normal tissue (called passive tumor targeting).

18. Combination Therapies
• Delivering multiple agents in vivo is complicated
because of their independent pharmacokinetics,
biodistribution, and clearance.
• Nanoparticle delivery systems can consolidate
these properties into one vehicle and increase
the likelihood that targeted tumor cells receive
both agents at a ratiometric dose.
• There have been several reports of codelivering
multiple anticancer agents using nanocarriers, and
some are reaching clinical trials.

19. THANKYOU