Page 26 - ITPS-8-2

INNOSC Theranostics and
Pharmacological Sciences The biochemical and biophysical guide for photodynamic therapy

In patients with small tumors, a reduction in tumor mass concluded that EUS-PDT for LAPC is safe and results in
and even remission were observed for several months. measurable tumor necrosis. A phase 2 trial is planned to
However, patients with widespread duodenal involvement further investigate these findings.
showed only a modest response.
5.1. The use of PDT in the treatment of pancreatic
Another study focused on patients with colorectal cancer
cancer metastases to the liver, a group with a poor
prognosis due to the scarcity of patients eligible for Pancreatic cancer is a condition associated with a high
8
curative liver resection. In this phase 1 trial, PDT was mortality rate. The primary treatment options are surgery
used to treat 31 liver metastases in 24 patients with or chemotherapy; however, an increasing number of
cases are diagnosed at advanced stages, making surgery
unresectable colorectal cancer metastases. PS 5, 10, 15,
20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC) infeasible. In addition, chemotherapy does not bring the
was administered intravenously at doses of 0.6 mg/kg or desired results due to the resistance exhibited by PCa
0.3 mg/kg. Tumors were illuminated for 300 – 600 s using cells. Given its high efficacy against cells resistant to
radiotherapy and chemotherapy, PDT has emerged as a
optical fibers inserted subcutaneously after 120 h, or after viable alternative for patients who are not candidates for
48 h in some subjects. The scattered light dose was 740 nm. surgery. Clinical practice has confirmed the effectiveness of
Results indicated tumor necrosis in all patients 1 month this minimally invasive treatment method. However, PDT
after PDT. A small proportion of patients reported mild faces several limitations when used in clinical settings,
pain, and the majority experienced transient subclinical including challenges related to insufficient delivery of
hepatotoxicity. No serious clinical complications were PSs, dependence on tumor oxygenation, and the ability
noted, except for pancreatic damage in one patient and of malignant tumors to evade treatment. To address
skin damage in another. Harmless side effects included these challenges, researchers are increasingly focusing on
transient phlebitis and mild skin phototoxicity from the development of PS nanoparticles (NPs) and various
excessive light during treatment. The study concluded that nanocarrier systems to enhance the cellular uptake and
PDT with mTHPBC is a safe and effective treatment for distribution of PSs within the body. Encapsulation of PSs
unresectable colorectal cancer liver metastases. in NPs significantly increases their accumulation in PCa
Meanwhile, one study showed that treatment with PDT tumors, owing to improved solubility and stability in
for locally advanced pancreatic cancer (LAPC) may be the bloodstream. Various strategies have been explored
limited due to the unfavorable prognosis associated with to develop multidrug codelivery NPs, which facilitate
the disease. The investigators hypothesized that PDT for synergistic PDT-based therapies, thereby enhancing the
9
LAPC is safe, technically feasible, and can lead to increased effectiveness and prolonging the therapeutic response. 10
tumor necrosis. In this phase 1 study, patients with While pancreatic surgery is technically challenging, PDT
untreated LAPC were administered intravenous porfimer offers a minimally invasive alternative. Despite its lower
sodium, followed by endoscopic ultrasound-guided invasiveness and promising potential for treating PCa, PDT
PDT (EUS-PDT) 2 days later. EUS-PDT was performed is not without its adverse effects, such as gastrointestinal
by puncturing the tumor with a 19-gauge needle, and a hemorrhage and duodenal obstruction. These side effects
1.0 cm diameter light diffuser emitting 630 nm light was are partly due to the limited selectivity of current PSs,
introduced. CT scans were conducted 18 days after PDT which results from their non-selective distribution. This
to assess pancreatic necrotic changes. Seven days following non-specific distribution creates a risk of photodamage
the CT scan, intravenous Nab-paclitaxel and gemcitabine to adjacent organs and prevents adequate accumulation
were administered weekly in a 3-week cycle until disease of PS at tumor sites. Furthermore, during follow-up after
progression or unacceptable cytotoxicity occurred. In PDT, some cases have shown liver metastasis and tumor
terms of primary outcomes, 12 patients with tumors regrowth at the edges of the treated area. It is believed
10
located in the head, neck, trunk, or tail of the pancreas that these phenomena may be attributed to insufficient
underwent EUS-PDT. In half of these patients, an increase oxygenation within the tumor. In addition, PDT alone is
in tumor volume and a higher percentage of tumor necrosis insufficient to fully combat cancer. As a result, specially
was observed in comparison to the initial imaging tests. modified NPs loaded with PSs are being used to enhance
After a follow-up period of 10.5 months, the median time PS solubility, improve oxygen consumption, and facilitate
to progression was 2.6 months, and the median overall more effective delivery. These NPs are often functionalized
survival was 11.5 months. During the treatment course, with special ligands that enable targeted delivery of PSs to
eight serious adverse events were reported, although none cancerous pancreatic cells, thereby significantly improving
of them were directly attributed to the therapy. The study the efficacy of PDT for PCa. As mentioned earlier, PDT

Volume 8 Issue 2 (2025) 20 doi: 10.36922/itps.4559