Periodic Reporting for period 1 - HypoCyclo (Multifunctional Polymeric Cyclodextrin Nanocarriers As Novel Triple-Negative Breast Cancer Treatment: A Versatile Photo-Chemotherapy Bypassing Hypoxic Conditions)
Período documentado: 2020-09-01 hasta 2023-08-31
The objective of the project is the combination of chemotherapy with photodynamic therapy in optimized conditions for the effective treatment of TNBC also in hypoxic conditions. We plan to prepare new polymeric nanoparticles able to load cancer drugs together with a photosensitizer for PDT as well as an oxygen releasing agent (ORA). The goal of the project is also to keep the synthetic protocols simple, low-cost and green, in order to facilitate industrial application of the nanoparticles that perform best.
The CyD polymer NPs successfully loaded the drug PCX, the photosensitizer Chlorin e6 and the anthracenic endoperoxide and the loaded NPs were completely characterized. First cell studies indicated that the neutral beta-CyD polymer is well tolerated while the positively-charged CyD polymer is more cytotoxic and thus not further explored. Currently the efficacy of the loaded system is investigated in BC cell lines.
Using the cyclodextrin-based polymer, the aromatic molecules were effectively dissolved in the mM range in water. After co-encapsulation of catalytic amounts of MB into the polymer and following the same protocol used in the case of organic solvents, the anthracenes ANBA and PABA were photochemically transformed in their endoperoxide analogues in PBS buffer (pH 7.4) of both D2O and H2O. This latter represents an extraordinary result as singlet oxygen has a much shorter lifetime in this solvent. Naphthalene-substrates, instead, were not suitable for photooxygenation neither in aqueous solvent. Cycloreversion of PABA-O2 was achieved upon heating in both organic and aqueous environments even though in conditions not yet compatible with in vivo applications.
Hence, the polymer acts both as solubilizing agent and reaction vessel enabling the photooxygenation in buffered water of hydrophobic substrates with an economical setup, comparable concentrations and improved reaction times with respect to the organic solvent. These results are of great importance for future exploitations in green synthesis and have the potential to launch CyD polymers as affordable hydrophilic platform for the development of more sustainable homogeneous photocatalytic protocols. Exploiting the versatility of the polymer to simultaneously solubilize different hydrophobic substrates bringing them in close proximity, also other types of reactions can be envisaged on hydrophobic molecules in aqueous environment. Moreover, once optimized the cycloreversion conditions, the use of a unique inexpensive polymeric matrix to solubilize, synthesize and deliver ORAs might definitively push the fast developments of new treatments for diseases displaying hypoxic environments.