Photodynamic Therapy: Illuminating a Cure for Cancer?

Nearly 40% of the world’s population will be diagnosed with some form of cancer in their lifetime.¹  The current treatment for such diseases usually includes a combination of invasive surgery, radiation, and chemotherapy. The focus is on chemotherapy as it is the first line treatment in most cases. This therapy often leads to side effects ranging from mild to severe, and it often is ineffective in a large percentage of cases as a mode of treatment. A relatively new technique, photodynamic therapy (PDT), uses a targeted laser to excite a photoactive complex which leads to cell apoptosis by the generation of reactive oxygen species.² This technique preserves healthy cells and has very few long term side effects. While this treatment could lead to a new era of cancer treatment, it does have its limitations including the need for increased accumulation of the photoactive complex in the tumor tissue at a non-toxic delivery level to healthy cells.

Recent research on PDT has employed the use of nanoplatform vehicles to increase the accumulation of the photoactive complex while shielding healthy cells by relying on the enhanced permeability and retention (EPR) effect.³ The EPR effect is employed due to an increase in the endothelial cell gap in angiogenic blood vessels created by the tumor to allow nanoparticles to accumulate and be retained in tumor cells more efficiently than in healthy cells. A number of these nanoplatform vehicles rely on pH responsive degradation to release multiple components for increased efficacy including alleviating the hypoxic environment of the tumor. This seminar will discuss several nanoplatforms^4-6 with the expectation of better understanding the characteristics necessary to improve upon the current PDT regimen. This research illustrates a method to encapsulate photoactive compounds in a hydrophilic nanoplatform for greater site specific concentration and retention while also alleviating the low oxygen concentration in the tumor microenvironment to maximize PDT ability and limit tumor growth.

References

1.  Institute, N. C. Cancer Statistics. https://www.cancer.gov/about-cancer/understanding/statistics

2.  DeRosa, M. C.; Crutchley, R. J., Photosensitized singlet oxygen and its applications. Coord. Chem. Rev. 2002, 233, 351-371.

3.  Albanese, A.;  Tang, P. S.; Chan, W. C. W., The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems. Annu. Rev. Biomed. Eng. 2012, 14, 1-16.

4.  Yang, G.;  Xu, L.;  Chao, Y.;  Xu, J.;  Sun, X.;  Wu, Y.;  Peng, R.; Lui, Z., Hollow MnO₂ as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses. Nat. Commun. 2017, 8, 902-915.

5.  Wang, D.;  Wu, H.;  Phua, S. Z. F.;  Yang, G.;  Lim, W. Q.;  Gu, L.;  Qian, C.;  Wang, H.;  Guo, Z.;  Chen, H.; Zhao, Y., Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment pf tumor. Nat. Commun. 2020, 11, 357-370.

6.  Dong, Z.;  Feng, L.;  Hao, Y.;  Chen, M.;  Gao, M.;  Chao, Y.;  Zhao, H.;  Zhu, W.;  Liu, J.;  Liang, C.;  Zhang, Q.; Liu, Z., Synthesis of Hollow Biomineralized CaCO₃-Polydopamin Nanoparticles for Mulitmodal Imaging-Guided Cancer Photodynamic Therapy with Reduced Skin Photosensitivity. J. Am. Chem. Soc. 2018, 140, 2165-2178.