| Sumario: | Background: Quercetin as a bioflavonoid with high anticancer potential, it has been proved to have a prospective applicability in chemotherapy for a series of cancers. PANC1, MCF7, CACO2, A375, A549 and PC3 cancer cell lines represent malignant neoplasms originating from respective pancreatic, breast, colorectal, skin, lung and prostate. The poor hydrophilicity of quercetin hinders its clinical usage in cancer therapy. Therefore, a strategy to improve the solubility of quercetin in water and/or enhance the bioavailability is desired. Aims: In attempting to present positive evidences that this drug delivery system of polymeric micelles is effective; Quercetin loaded polymeric nanomicelles vs. free Quercetin were coincubated with selected 3 branched chain aminoacids (BCAAs; Val, Leu and Ile)) to examine synergy in chemosensitizing a panel of 6 cancer cell lines, thus reducing the dose used to submicronanomolar affinities of greater antiproliferation potencies than cisplatin's. Results: Quercetin loaded nanomicelles were proved of significantly less DPPH radical scavenging activity vs. both the antioxidative ascorbic acid and free quercetin. Unlike indomethacin; in lipopolysaccharide induced RAW264.7 macrophages inflammation; quercetin loaded nanomicelles had picomolar affinity for nitric oxide (NO) radical scavenging activity. Free quercetin posed inferior micromolar antiinflammation capacity vs. quercetin loaded nanomicelles, though more potent substantially vs. indomethacin. Remarkably nanocarrier formulation of quercetin was proved of significantly more potent antineoplastic bioactivity with micromolar affinities in the adherent monolayers 6 cancer cell lines vs. both free quercetin's and cisplatin's. Exquisitely in PC3 monolayers; free quercetin was more potent than cisplatin (IC50 values (µM) 46 vs. 102; P<0.01) and chemosensitized cotreated less potent aminoacids (IC50 values (µM) 119-557); quercetin loaded nanomicelles posed substantially greater synergy in growth suppression potencies of cotreating aminoacids vs. both free quercetin and cisplatin's (IC50 values (µM) <50-100 vs. cisplatin's 102 and free quercetin; P<0.05-0.001) thus reducing their doses used against PC3 tumour cells. Val, Leu and Ile exhibited inferior reduction of viability capacities when compared to cisplatin in adherent monolayers of all 6 cancer cells. Equally free quercetin had suboptimal micromolar growth inhibition (200-300µM range except for skin A375 cancer cells) as compared to antineoplastic proapoptogenic cisplatin in all 4 cancer cell lines (>100µM). Quercetin cotreated PANC1 wells of Val exhibited significantly chemosensitizing antiproliferation affinities (P<0.05 vs. cisplatin's 25.6). Remarkably most appreciable synergy trends were obtainable in resistant CACO2 and MCF7 for all quercetin cotreated 3 BCAAs separately. Surprisingly; although quercetin loaded nanomicelles could chemosensitize quercetin cytotoxicity in all 6 cancer adherent monolayers; quercetin loaded nanomicelles failed to perform similarly in aminoacids incubations (except for PC3 cancer cells). Conclusion: Our study indicated that Quercetin loaded polymeric nanomicelles were a novel submicro-nanoagent of Quercetin with an enhanced antitumor activity, which could serve as a promising potential candidate for chemotherapy of a diversity of cancers.
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