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Table 1. Current nanoplatforms under preclinical development for colorectal cancer [58-62]
Formulation Ligand Target
Nanosized particle Antibody Carcinoembryonic antigen (CEA)
Dextran and PEG-coated superparamagnetic Single-chain Fv antibody fragment (scFv) CEA
iron oxide nanoparticles
Gold and iron oxide hybrid nanoparticle scFv A33 antigen
Polymer capsules Humanized A33 monoclonal Fas receptor
Chitosan nanoparticles loaded with Folic acid HT29 colorectal cancer cell lines overexpressing
5-aminolaevulinic acid folate
HPMA-copolymer-doxorubicin conjugates Peptide GE11 A431, HT29 and SW480 cell lines
Mesoporous silica nanoparticle Coated with poly-(L-lysine) and hyaluronic HCT-116 cancer cells
PEG: polyethylene glycol; HPMA: hydroxypropyl methacrylate

types of nanoparticles. RES effect refers to the quick absorption of nanoparticles by macrophages which
usually results in clearing nanoparticles from the circulation in vivo [51-53] . Specific types of nanoparticle
coating may prevent and minimise the RES effect. Nanoparticles with surfactants or covalent linkage of
[54]
polyoxyethylene have shown to effectively minimise the RES effect . The size and shape of nanoparticles
are the other two main factors that affect the delivery of conventional therapeutics to solid tumours.
Nanoparticles larger than 500 nm are shown to be rapidly removed from the circulation in vivo [44,55] .
In addition, targeted nanoparticles as a drug delivery system based on monoclonal antibodies are
currently one of the main approaches for CRC therapy under preclinical development [56,57] . A list of these
nanoplatforms is presented in Table 1.

LIPOSOMES-BASED NANOPARTICLES
[63]
The first therapeutic nano-platform applied in medicine was introduced by Bangham et al. in 1961. This
nano-platform was based on liposomes which were the first drug-delivery system approved by FDA for
clinical practice. Liposome-based nanoparticles are one of the commonly used nanoparticles for delivering
small peptides, nucleic acids, and proteins in nano-platform drug delivery [64-66] . Nanoliposomes are non-
toxic, spherical nano-carriers containing an aqueous core with phospholipid bilayer [67,68] . Nanoliposomes
are considered as one of the most effective drug delivery systems at a cellular level. This is mainly due
to their size, ability to incorporate various substances and slow-releasing and targeting characteristics
which also results in decreasing side effects [69,70] . There are three main types of nanoliposomes: (1) stealth
liposomes or long-circulating liposomes, which have a modified phospholipid bilayer structure and added
gangliosides or a polyethylene glycol (PEG) to assist avoiding blood plasma opsonins proteins binding
to the liposome surface and minimise the RES effect; (2) active nanoliposomes: this type of nanoparticle
targets receptors, hormones, peptides and antibodies; and (3) sensitive nanoliposomes: they are special
active nanoliposomes with unique properties such as pH-sensitive, thermo-sensitive and magnetic [21,70,71] .
[72]
Doxorubicin (Doxil®)-liposome is an example of FDA approved nanoliposome for chemotherapy for CRC .
Doxil is approximately 100 nm and although it has much less gastrointestinal and cardiac toxicity, it causes
[73]
other side effects such as redness and peeling of the skin . Marqibo® is another recent nanoliposomal
drug approved by FDA [74-76] . Marqibo is approximately 100 nm and it is a cell cycle-dependent anticancer
drug. Thermo-sensitive liposome doxorubicin (Thermodox®) is another promising nanoliposomal drug for
[77]
colorectal liver metastases in combination with radiofrequency ablation . Thermodox® is a nanoliposomal
[77]
with doxorubicin formulation which releases the drug upon a mild hyperthermic trigger . Thermodox
[77]
can deliver 25 fold more doxorubicin into tumours than IV doxorubicin does .

CORE-SHELL NANOPARTICLES
There has been an increasing interest in developing and synthesizing core-shell nanoparticles [78,79] . The
core-shell nanoparticles are composed of two or more materials which can be synthesised with different