Welcome to DU! The truly grassroots left-of-center political community where regular people, not algorithms, drive the discussions and set the standards. Join the community: Create a free account Support DU (and get rid of ads!): Become a Star Member All Forums Issue Forums Culture Forums Alliance Forums Region Forums Support Forums Help & Search

NNadir

(33,368 posts)
Sun Oct 8, 2017, 05:17 PM Oct 2017

Conjugated Polymeric Photosensitizers for Photodynamic Cancer Therapy.

I stumbled upon a very cool paper this afternoon on cancer therapy.

It's here: Two-Dimensional Fully Conjugated Polymeric Photosensitizers for Advanced Photodynamic Therapy (Dai et alChem. Mater., 2016, 28 (23), pp 8651–8658)

Many people are aware that radiation can both cause and cure cancer - sometimes do both - and the mechanism by which this takes place often involves highly energetic species, often free radicals. Of course, "radiation" is a broad term; it applies not just high energy radiation, but also to light, radio waves, microwaves and radiant heat (infrared). The most efficient forms of energy for providing free radicals are high energy, UV radiation (as in the generation of sunburns and melanoma), x-rays, and gamma rays. However, under certain circumstances lower energy radiation can generate reactive species. That's what this paper refers to doing.

Photodynamic therapy is a therapy that generates reactive oxygen species (high energy species) that can react locally with cancer cells and kill them. However since human tissue is opaque, the idea is to use light waves that can penetrate tissue without depositing energy. As people who have used microwaves and understand something about how they work, know, radio and infrared radiation can do this.

From the introductory text:

Photodynamic therapy (PDT) has attracted tremendous attention as an emerging clinical modality for treatment of neoplastic and nonmalignant lesions, including cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate, and skin, to name a few.(1-3) PDT generally involves photoexcitation of a photosensitizer, which transfers energy to surrounding O2 to generate reactive oxygen species (ROS), especially singlet oxygen (1O2),(4) to impart a selective irreversible cytotoxic process to malignant cells with respect to noncancerous tissues. PDT with an optical precision could show a minimal toxicity to normal tissues, negligible systemic (organ) or long-term effect, and excellent cosmetic appeal. However, the near-infrared (NIR) light is often required to effectively penetrate biological tissues, such as skin and blood, with minimal normal tissue damage.(2, 4) This is because visible light below 700 nm cannot penetrate deep into tissues with a high level of endogenous scatters and/or absorbers, such as oxy-/deoxy-hemoglobin, lipids, and water, in skin and blood.(5) Therefore, it is important to develop efficient photosensitizers with strong absorption in the desired therapeutic window (particularly, 700–1000 nm) for advanced PDT.

Porphyrin, a conjugated macrocycle with intense optical absorption, plays important roles in our life (e.g., in heme to act as a cofactor of the protein hemoglobin) and has been widely used as a photosensitizing reagent for PDT.(2) Due to the short conjugation length intrinsically associated with individual porphyrin macrocycles of a limited size, however, most of the clinically approved porphyrin-based photosensitizers show optical absorption well below 700 nm with insignificant absorption within the tissue transparency window (e.g., 700–900 nm)2. As a typical example, porfimer sodium (Photofrins), one of the widely used clinical PDT agents, with oligomeric porphyrin units being linked by nonconjugated ester and ether linkages to gain solubility, shows diminished absorption above 630 nm.(6) Therefore, it is highly desirable to develop new photosensitizers of a long conjugation length with alternating C–C single and C═C double bonds, and hence efficient absorption within the tissue transparency window (e.g., 700–900 nm).


Here's a picture of the molecules they make:



The reactive molecule they generate with these species is "singlet oxygen"

Mechanism study on singlet oxygen generation

To study the mechanism of singlet oxygen generation from photoirradiation of COP-P-SO3H, we performed the first-principles calculations with B3LYP hybrid density functional theory with the Gaussian program(15) based on the cluster model derived from the above experimental characterization data. Our calculations revealed that O2 molecules prefer to adsorb via the Yeager model(12, 27) (Figures S8–17 and Table S2) in COP-P-SO3H and that the optimized O2 adsorption site is on the top of the H-free pyrrolic N in the porphyrin ring (Figure S13). Furthermore, our molecular orbital calculations indicated that the HOMO is almost entirely localized in the porphyrin ring, being dominantly associated with the σ-bonding orbital from the pyrrolic N (No. 22 and No. 24 in Figure S18) and the π-bonding orbital from the pyrrolic and methine bridge carbons in the porphyrin ring, while the LUMO is mainly associated with the σ-antibonding orbital from oxygen molecules and the π-antibonding orbital from the pyrrolic ring and the methine bridge carbon in the porphyrin (Figure 7A). Clearly, therefore, the charge density distribution calculations indicate that the electron was dominantly transferred from pyrrolic N (No. 24 in Figure S18) to an oxygen molecule when it approached the porphyrin ring (Figure S19).


The conclusion:

In summary, we have, for the first time, developed a well water-dispersive, fully conjugated two-dimensional covalent organic polymer (i.e., COP-P-SO3H) via a facile and scalable, but very efficient and cost-effective, Yamamoto Ullmann cross-coupling of multiple porphyrin macrocycles through conjugated linkages followed by sulfonation. The resultant COP-P-SO3H of a good dispersiveness and low band gap exhibited strong optical absorption up to 1100 nm and acted as an efficient photosensitizer for advanced photodynamic therapy with a 20% higher singlet oxygen quantum yield than that of the clinically used protoporphyrin IX (PPIX), but a negligible cyto-/genotoxicity without light exposure. Compared to those isolated porphyrin macrocycles (e.g., PPIX, TBBPP), COP-P-SO3H, with fully conjugated multiple porphyrin macrocycles, could effectively generate singlet oxygen species during the PDT process to efficiently kill the breast tumor cells (MDA-MD-231 cells) through successive DNA damage, as revealed by the combined experimental and theoretical approach used in this study. This is the first time for 2D covalent organic polymers (COPs) to be used as efficient photosensitizers of practical significance for advanced PDT. This work clearly opens up exciting new applications for COPs as well as new avenues for the development of other novel 2D COPs for advanced cancer therapy and beyond.


The nice graphic overview:



Cool I think.

Enjoy your Sunday evening.

8 replies = new reply since forum marked as read
Highlight: NoneDon't highlight anything 5 newestHighlight 5 most recent replies

NNadir

(33,368 posts)
3. This is very early discovery work, if I understand it well, and it comes out of China.
Sun Oct 8, 2017, 06:18 PM
Oct 2017

It's promising research, I'm sure, but it may not even have advanced to clinical trials.

Many things which are interesting and exciting in the lab don't pan out.

hedda_foil

(16,368 posts)
2. A dear friend of mine had a quick killing cancer and they used photon radiation on him.
Sun Oct 8, 2017, 05:55 PM
Oct 2017

For the medical types, it was small cell carcinoma of the thymus with a single metastasis to the lung. He was told that if the first and only therapy failed, he had 3-6 months. . He had massive chemo along with the photon therapy.

It worked. This week, it's been 3 years since diagnosis. Oh be it could recur, but the treatment performed pretty close to a miracle.

NNadir

(33,368 posts)
7. It may be a misprint of chlorosulfonic acid.
Mon Oct 9, 2017, 12:27 PM
Oct 2017

From the text:

Synthesis of COP-P-SO3H. COP-P was degassed at 200 °C for 24 h prior to use. Chlorosulfonic acid (4 mL) was added into 40 mL of dichloromethane solution containing 400 mg of degassed COP-P in an
ice-bath.
Latest Discussions»Culture Forums»Science»Conjugated Polymeric Phot...