Introduction

Physically remove cancerous parts

 Invalid for highly-metastatic tumors
 Loss of an organ
 Risk of cancer recurrence

Surgery

Chemotherapy Tumor Surgery

Destroy tumor cells with radiation
Chemically poisoning tumor cells  Low efficacy
 High toxicity
 The surrounding healthy cells get burnt
 Easily acquire multi-drug resistance
 May develop a secondary cancer
 Nanotechnological drug delivery system
Inorganic nanomaterials Organic nanomaterials Hybrid nanomaterials

Advantages Advantages Advantages

- Unique electrical, magnetic, optical - Precise control of particle characteristics - Optical properties
properties - Payload flexibility - High biocompatibility
- Variability in size, structure, geometry - Easy surface modification - High catalytic activity
- Suited for theragnostic application

Disadvantages Disadvantages Disadvantages

Toxicity and solubility limitation Possibility of aggregation and toxicity Possibility of toxicity and degradation

Wu P, Han J, Gong Y, Liu C, Yu H, Xie N. Nanoparticle-based drug delivery systems targeting tumor microenvironment for cancer immunotherapy resistance: Current advances and applications. Pharmaceutics. 2022;14(10):1990
 Targeted drug Carrier/Delivery system

The concept of drug targeting system includes the coordinating behavior of

three components:

- Target moieties
- Carriers
- Therapeutic drug

Targeting moieties:
- Antibodies - Charged molecules
- Proteins - Polysaccharides
- Lipoproteins - Low molecular weight ligands
- Hormones
 Mechanisms of targeted nanocarriers

Normal tissues Cancerous tissues

There are two major mechanisms:

 Passive targeting

 Active targeting

Sun T, Zhang Y, Pang B, Hyun DC, Yang M, Xia Y. Engineered nanoparticles for drug delivery in cancer therapy. Angewandte Chemie. 2014;53
46:12320-64

Differential uptake of NPs and small molecules based on their size

across normal and cancerous tissues.
 Mechanisms of targeted nanocarriers

Passive targeting

Enhanced permeability
and retention (EPR)
effect
- Leaky blood vessels
(endothelial pores:
100 – 600 nm)

- Poor lymphatic
drainage
 Mechanisms of targeted nanocarriers
Nanoparticle size, shape and surface charge dictate biodistribution among the different
organs including the lungs, liver, spleen and kidneys

Blanco, E.; Shen, H.; Ferrari, M. Principles of Nanoparticle Design for Overcoming Biological Barriers to Drug Delivery. Nat. Biotechnol. (2015), 33, 941–951.

- Particles with 2000 nm accumulate readily within the spleen and liver.
- NPs in the range 100 -200 nm have been shown to extravasate through vascular fenestration of tumor (EPR effect)
- NPs shapes exhibit unique flow characteristics which affect biodistribution among the different organ.
- Neutural and negatively charged NPs have long circulation lifetimes and less accumulations.
 Mechanisms of targeted nanocarriers

Active targeting
- Delivery drugs, gene and
theragnostic to the local
of interest
- Avoiding the normal
tissue
- Enhance the therapeutic
efficiency
- Limit side effects
 Targeted drug Carrier/Delivery system

Large DE, Soucy JR, Hebert J, Auguste DT. Advances in receptor-mediated, tumor-targeted drug delivery.
Advanced Therapeutics. 2019;2(1):1800091