Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice.
The power of tumorigenesis, chemo-resistance and metastasis in malignant ovarian tumors resides in a tiny population of cancer cells known as ovarian cancer stem cells (OCSCs). Developing nano-therapeutic targeting of OCSCs is considered a great challenge. The potential use of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) was investigated as a drug delivery system for paclitaxel (PTX) against OCSCs in vitro and in vivo. PTX-loaded PLGA NPs were prepared by an emulsion solvent evaporation method, supported by incorporation of folic acid (FA) as the ligand. NPs were characterized for size, surface morphology, drug loading, and encapsulation efficiency. In vitro cytotoxicity of PTX-loaded FA/PLGA NPs was tested against OCSCs with MTT assay. In vivo anti-tumoral efficiency and active targeting potential of prepared NPs against tumors in nude mice were investigated. In vitro results revealed that IC50 of PTX was significantly reduced after loading on PLGA NPs. On the other hand, in vivo results showed that PLGA NPs enhanced the tumor suppression efficiency of PTX. Investigation with real time quantitative PCR analysis revealed the limiting expression of chemo-resistant genes (ABCG2 and MDR1) after applying PLGA NPs as a drug delivery system for PTX. Histopathological examination of tumors showed the effective biological influence of PTX-loaded FA/PLGA NPs through the appearance of reactive lymphoid follicles. Targeting potential of PTX was activated by FA/PLGA NPs through significant preservation of body weight (p < 0.0001) and minimizing the systemic toxicity in healthy tissues. Immunohistochemical investigation revealed a high expression of apoptotic markers in tumor tissue, supporting the targeting effect of FA/PLGA NPs. A drug delivery system based on FA/PLGA NPs can enhance PTX's in vitro cytotoxicity and in vivo targeting potential against OCSCs.
['Abou-ElNaga|Amoura|A|', 'Mutawa|Ghada|G|', 'El-Sherbiny|Ibrahim M|IM|', 'Abd-ElGhaffar|Hassan|H|', 'Allam|Ahmed A|AA|', 'Ajarem|Jamaan|J|', 'Mousa|Shaker A|SA|']
D000818:Animals D000970:Antineoplastic Agents D045744:Cell Line, Tumor D004195:Disease Models, Animal D005260:Female D006801:Humans D019344:Lactic Acid D051379:Mice D008819:Mice, Nude D050997:Nanomedicine D053758:Nanoparticles D014411:Neoplastic Stem Cells D010051:Ovarian Neoplasms D017239:Paclitaxel D011100:Polyglycolic Acid D000077182:Polylactic Acid-Polyglycolic Acid Copolymer D047368:Tumor Burden D023041:Xenograft Model Antitumor Assays
ovarian cancer stem cells nude mice PLGA drug delivery system paclitaxel