**7. Active targeting biomolecules for enhanced PS drug delivery and PDT**

Active PDT PS drug delivery involves the conjugation of the PS drug to specific ligands or biomolecules moieties, which are complementary to overexpressed cancer cell receptors and so via a molecular recognition process PS drug uptake in target tumor cells is enhanced [31]. These moieties include monoclonal antibodies (mAb), proteins (e.g. transferrin), nucleic acids (aptamers), small molecules (folic acid), polymers (hyaluronic acid) and peptides (proteins), which are over-expressed on CRC tumor cells only [31, 96]. These specific ligands or biomolecules moieties, which are conjugated to a PS NP drug delivery system, have a specific affinity for receptors that are over-expressed on CRC tumor cells and their vascular, but not on normal cells [34]. This facilitates enhanced PSs retention in tumor target sites only, improving the efficacy of PDT and localizing its treatments effectiveness to killing CRC tumors only [34]. Common protein receptors in CRC cells which have been noted to be overexpressed and so can be utilized for possible PS active drug targeting include: epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), epithelial cell-adhesion molecule (EpCAM), carbonic anhydrase IX (CA IX), peroxisome proliferator-activated receptor γ (PPARγ), cyclooxygenase-2 (COX-2), cholesterol and low-density lipoprotein, estrogen receptors, cholecystokinin A receptors, lectin saccharide receptors, anti-DR5 antibody, as well as cluster of differentiation 44, 133, 166 and 24 (CD44+, CD 133+, CD166+ and CD24+) [13, 97–99]. Recent research approaches to enhance PS NP drug delivery by actively targeting CRC tumors using various moieties and so increase the efficacy of PDT have been listed in **Table 3**.

**53**

*Targeted Photodynamic Therapy as Potential Treatment Modality for the Eradication of Colon…*

**Remarks Ref.**

[100]

[46]

[101]

[102]

[103]

[104]

[105]

[106]

[107]

[108]

[109]

[110]

Eudragit S100 is a pH responsive enteric polymer and citrus pectin is a ligand receptor for galectin-3. Targeted drug delivery was found both *in vitro* and *in* 

Cationic electric charge of photoimmune-conjugate enhanced PS delivery and showed a 90% phototoxic

Drug conjugate reported >500-fold increase in toxicity upon light activation in HT-29CRC cells and was not cytotoxic towards cell types without

Colon carcinoma *in vitro* CT26 cell lines showed targeted uptake with enhanced apoptotic cell death.

Effective tumor targeting noted with tumor growth being significantly suppressed and inhibited by 9.61 ± 1.09-fold in human colon HT29 cell line and

Enhanced uptake in human colon cancer xenograft model was observed with significant tumor

PDT induced significant targeted immunogenic apoptotic cell death in a syngeneic CT26 mouse tumor

Reported significant increase in tumor suppressor CDKN1A gene in CRC model with enhanced uptake

Within Murine CT26 colon carcinoma cells and CT26 tumor-bearing mice notable targeting and tumor

Drug carrier was successfully transported into *in vitro* WiDr CRC cells via photochemical internalization (PCI) and resulted in 90% cytotoxic response.

PDT PS with Avastin™ and monoclonal antibody in murine model, reported even lowered expression of VEGF in tumors with improved tumor killing efficacy than when compared to anti-angiogenic chemotherapeutic Avastin™ and monoclonal antibody treatment alone (which indirectly kills cells by via vascular damage), suggesting that PDT PS contributed to overall combined treatment approach by directly killing cells via ROS generation as well, and

Photothermal therapy of colon cancer cells exhibited

*vivo* with enhanced PDT cytotoxic effects.

effect within *in vitro* HT-29CRC cells.

O-glycan-peptide markers.

murine tumor model.

model (allograft model)

suppression was observed.

so improved CRC cell death.

notable cell death.

and PDT effects.

destruction.

*DOI: http://dx.doi.org/10.5772/intechopen.84760*

coated citrus pectin nanoparticles

conjugates (murine monoclonal antibody

aptamers were bound to unique short O-glycanpeptide signatures

Biotinylated to target biotin receptors

nanoparticle to target CD 44 receptors

inhibitor sodium phenylbutyrate (NaPB)

transferrin-IR780 for direct Transferrinreceptor (TfR) targeting

IM7-saporin immunotoxin CD44 targeting receptor

Bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody

gold coated

superparamagnetic iron oxide nanoparticles conjugated with thiol modified MUC-1 aptamers

conjugated to 5β-cholanic acid (5β-CA) to target CD44

ligands

Chlorin e6 (Ce6) Glycoconjugated chlorin (G-chlorin)

Hypericin Histone deacetylase

IR780 iodide Self-assembled

None Photothermal

Meso-tetraphenyl chlorin disulfonate (TPCS2a)

tetra(hydroxyphenyl) chlorin (mTHPC)

Meta-

*In vitro* **and** *in vivo* **PDT CRC research Photosensitizer Active drug delivery system**

Chlorin e6 (Ce6) Site specific immune-

Chlorin e6 (Ce6) Phototoxic DNA

Chlorin e6 (Ce6) Hyaluronic acid

Chlorin e6 (Ce6) Hyaluronic acid

Chlorin e6 (Ce6) and

indium

17.1A)

5-Fluorouracil Eudragit S100

*Targeted Photodynamic Therapy as Potential Treatment Modality for the Eradication of Colon… DOI: http://dx.doi.org/10.5772/intechopen.84760*


*Multidisciplinary Approach for Colorectal Cancer*

*In vitro* **and** *in vivo* **PDT CRC research**

Protoporphyrin IX (PpIX) Non-biodegradable

Zinc protoporphyrin (ZnPP) N-(2-hydroxypropyl)

Zinc(II) phthalocyanine Tetronic® 1107

SN-38-Cyclodextrin Complexation

silica

Chlorin-core star-shaped block copolymer (CSBC)

methacrylamide copolymer with PEG

micelles

**7. Active targeting biomolecules for enhanced PS drug** 

*Passive Targeting PDT PS drug delivery mechanisms within in vitro and in vivo CRC.*

polymeric poloxamine micelles (T1107)

Active PDT PS drug delivery involves the conjugation of the PS drug to specific ligands or biomolecules moieties, which are complementary to overexpressed cancer cell receptors and so via a molecular recognition process PS drug uptake in target tumor cells is enhanced [31]. These moieties include monoclonal antibodies (mAb), proteins (e.g. transferrin), nucleic acids (aptamers), small molecules (folic acid), polymers (hyaluronic acid) and peptides (proteins), which are over-expressed on CRC tumor cells only [31, 96]. These specific ligands or biomolecules moieties, which are conjugated to a PS NP drug delivery system, have a specific affinity for receptors that are over-expressed on CRC tumor cells and their vascular, but not on normal cells [34]. This facilitates enhanced PSs retention in tumor target sites only, improving the efficacy of PDT and localizing its treatments effectiveness to killing CRC tumors only [34]. Common protein receptors in CRC cells which have been noted to be overexpressed and so can be utilized for possible PS active drug targeting include: epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), epithelial cell-adhesion molecule (EpCAM), carbonic anhydrase IX (CA IX), peroxisome proliferator-activated receptor γ (PPARγ), cyclooxygenase-2 (COX-2), cholesterol and low-density lipoprotein, estrogen receptors, cholecystokinin A receptors, lectin saccharide receptors, anti-DR5 antibody, as well as cluster of differentiation 44, 133, 166 and 24 (CD44+, CD 133+, CD166+ and CD24+) [13, 97–99]. Recent research approaches to enhance PS NP drug delivery by actively targeting CRC tumors using various moieties and so increase the efficacy of PDT have been

**Photosensitizer Nanoparticle Remarks Ref.**

Zinc phthalocyanine Liposomal CRC CT26 tumor models which received PDT and

Zinc phthalocyanine Titanium dioxide Improved uptake and enhanced theranostics of

generation.

applications.

120 days.

(HT29) cells.

Improved PS accumulation in both HCT-116 cell lines and tumor bearing mice, with enhanced ROS

sonodynamic therapy tumors shrank by 20% after

PDT within *in vitro* colorectal adenocarcinoma

Nanodrug caused necrosis and disappearance of >70% of tumors in colon cancer mouse models.

Improved uptake and enhanced PDT apoptotic cell death within *in vitro* 2D and 3D murine colon

adenocarcinoma CT26 cells.

Combination of PS and chemotherapy nanocarrier showed 60% tumor regression in HT-29 human CRC xenograft model, after three [90]

[91]

[92]

[93]

[94]

[95]

**delivery and PDT**

**Table 2.**

**52**

listed in **Table 3**.


### **Table 3.**

*Active Targeting PDT PS drug delivery mechanisms within in vitro and in vivo CRC.*
