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Abstract
BackgroundCancer has been conquered by recent advances in chemotherapy, targeted therapy, and their combinations. However, 90 % of cancer patients die due to cancer recurrence or metastasis. Cancer cell change their metabolic properties to metastasize, changing from conventional glycometabolism to fat metabolism. This is because cancer cells are mainly spread through lymphatic system, which responsible for the absorption and transport of fatty acids and fats. Therefore, cancer cells ahead of metastasis specifically absorb fat to produce energy. Using this property, a photodynamic therapeutic agent conjugated with fatty acids (oleic acid, OA) capable of targeting metastatic cancer cells was developed.Main bodyPolymeric photosensitizer conjugated with OA were composed biocompatible polymers (pullulan) and photosensitizers (chlorin e6, Ce6) (OA-Pullulan-Ce6, OPuC). Pullulan consists of various repeated units, and it is possible to maximize the effects of OA and Ce6 by binding several them to one repeated unit. In this study, the interaction and detection potency of OPuC with cancer cells was confirmed using colon, breast, and lung cancer cell lines. In metastatic cancer cell, OPuC exhibited 3.27-fold higher cellular internalization than non-OA conjugated polymer (Pullulan-Ce6, PuC), however, in negative cell, the variation between OPuC and PuC was negligible despite the existence of OA (1.86-fold). OPuC accumulated in cancer cells could generate singlet oxygen under laser irradiation, resulting in cellular apoptosis and necrosis. Hereby, we proved that OA conjugated polymeric photosensitizer will be a potential metastatic cancer targeting photodynamic therapeutic agent.ConclusionCancer cells actively receive OA conjugated polymeric photosensitizers for fat metabolic pathway, compared with normal cells. Therefore, a new type of polymeric photosensitizer using cancer metabolic properties has potency in metastatic cancer therapy.
Highlights
Cancer has been conquered by recent advances in chemotherapy, targeted therapy, and their combinations
Synthesis and characterization of Oleic acid-Pullulan-Chlorin e6 (Ce6) (OPuC) The synthesized OPuC was analyzed by 1H-NMR and quantified the concentration of Ce6 via UV-vis spectrometer
Peak of 1H-NMR showed conjugated Ce6 on PuC and OPuC, and the OPuC spectra contained the peak of Oleic acid (OA) (Fig. 1b)
Summary
Cancer has been conquered by recent advances in chemotherapy, targeted therapy, and their combinations. 90 % of cancer patients die due to cancer recurrence or metastasis Cancer cell change their metabolic properties to metastasize, changing from conventional glycometabolism to fat metabolism. This is because cancer cells are mainly spread through lymphatic system, which responsible for the absorption and transport of fatty acids and fats. Cancer cells ahead of metastasis absorb fat to produce energy Using this property, a photodynamic therapeutic agent conjugated with fatty acids (oleic acid, OA) capable of targeting metastatic cancer cells was developed. Cancer metastasis refers to the dissemination of cancer cells from the primary tumor to other organs via the systemic circulation, a sentinel lymph node [6,7,8]. Taking (2020) 24:1 notice of these cancer cell properties, photosensitizers conjugated fatty acids have been developed, which can be expected to selectively kill metastatic cancer by photodynamic therapy (PDT)
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