Ph-Responsive Photinia Glabra–Zinc Oxide–Protoporphyrin IX Nanoconjugates With Enhanced Cellular Uptake for Photodynamic Therapy Towards Cancer Cells

Abstract

Background: Photodynamic therapy (PDT) of cancer has been limited by the poor solubility of most photosensitizers, use of high drug dosages, and the pH difference between the tumor tissue microenvironment (slightly acidic) and the bloodstream. These affect cellular uptake, selectivity and singlet oxygen generation. Materials & methods: We formulated Photinia glabra–green synthesized zinc oxide–protoporphyrin IX (PG–ZnO–PP) nanoconjugates by conjugating the ZnO nanoparticles enriched with amino groups and PP. Results: PG–ZnO–PP nanoconjugates showed higher rate of reactive oxygen species generation, improved cellular uptake in the acidic pH and lower IC₅₀ toward Eca-109 cells for PDT. Conclusion: PG–ZnO–PP nanoconjugates are a potential solution to reducing drug dosage of PP through improved drug uptake, for enhanced targetability and reduced skin photosensitivity with improved PDT efficacy.

Plain language summary

The progress of treating cancer using light-sensitive drugs and laser light of known wavelength has been limited by the poor solubility of most light-sensitive drugs, the use of high drug dosages and the slightly acidic environment within the cancerous tissues compared with normal blood in the body. These affect the ability of drugs to accumulate in cancerous cells, and not the normal cells, and the ability to produce the oxygen species that are toxic to the cancerous cells. In this paper, we prepared nanoparticles from zinc acetate using Photinia glabra (PG) fruit extract which were then used to chemically react with a light-sensitive drug called protoporphyrin IX (PP) to formulate small particles known as PG–zinc oxide (ZnO)–PP nanoconjugates. Our results showed that PG–ZnO–PP nanoconjugates had the ability to produce the toxic oxygen particles at a high rate and in good quantity. They also had a higher capability to accumulate in the cancerous cells at a pH below 7 with lower values of the drug needed to cause 50% of cell death toward the cancerous cells which affect the tube that connects from the throat to the stomach when projected with laser light. We could consider PG–ZnO–PP nanoconjugates to serve as a potential solution for reducing the dosage of PP needed to treat cancer in the presence of laser light, and at the same time they can help to reduce the skin-related side effects for patients after treatment when exposed to light.

Tweetable abstract

pH-responsive PG–ZnO–PP nanoconjugates with enhanced cellular uptake in tumor tissue microenvironment which is slightly acidic, and reactive oxygen species and singlet quantum yield with a lower dosage of protoporphyrin IX, for improved photodynamic therapy of cancer, thereby reducing skin photosensitivity.

Keywords::

• cancer
• green synthesis
• nanoconjugate
• nanoparticle
• photodynamic therapy
• protoporphyrin IX

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2023-0242

Author contributions

The manuscript was written and revised through contributions of all authors. All authors have read and agreed to the final version of this manuscript.

Financial disclosure

This work was supported by the Foundation of Science and Technology Commission of Pudong New Area (nos. PKJ2019-Y31, PKJ2020-Y42), National Natural Science Foundation of China (no. 21977016), Foundation of Shanghai Science and Technology Committee (nos. 20430730900, 20490740400, 21430730100, 23S11901600 and 21MC1930200), the Grant of the Ministry of Science and Technology of China (no. 9-11) and grant of Dudan University (IDF163011). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the Foundation of Science and Technology Commission of Pudong New Area (nos. PKJ2019-Y31, PKJ2020-Y42), National Natural Science Foundation of China (no. 21977016), Foundation of Shanghai Science and Technology Committee (nos. 20430730900, 20490740400, 21430730100, 23S11901600 and 21MC1930200), the Grant of the Ministry of Science and Technology of China (no. 9-11) and grant of Dudan University (IDF163011). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.