Precise engineering of Gemcitabine prodrug cocktails into single polymeric nanoparticles delivery for metastatic thyroid cancer cells

Abstract

GLOBOCAN estimates 36 types of cancers in 185 countries based on the incidence, mortality, and prevalence in the year 2019. Nowadays, chemotherapy is the most widely used cancer treatment among immune, radio, hormone, and gene therapies. Here, we describe a very simple yet cost-effective approach that synergistically combines drug reconstitution, supramolecular nano-assembly, and tumor-specific targeting to address the multiple challenges posed by the delivery of the chemotherapeutic Gemcitabine (GEM) drug. The GEM prodrugs were gifted to impulsively self-assemble into excellent steady nanoparticles size on covalent conjugation of linoleic acid hydrophobic through amide group with $100 nm. Newly synthesized GEM-NPs morphology was confirmed by various electron microscopic techniques. After successful synthesis, we have evaluated the anticancer property of GEM and GEM-NPs against B-CPAP (papillary thyroid carcinoma) and FTC-133 (human follicular thyroid carcinoma) cancer cell lines. Further studies such as AO-EB (acridine orange-ethidium bromide), nuclear staining and flow cytometry analyses on cell death mechanism signified that the cytotoxicity was associated with apoptosis in thyroid cancer cells. GEM-NPs show excellent biocompatibility compared to GEM. The present study explained that GEM-NPs as a safe and hopeful strategy for chemotherapeutics of thyroid cancer therapy and deserve for further clinical evaluations.

Development of Polymer-Assisted Nanoparticles and Nanogels for Cancer Therapy: An Update

“…MET-PLGA-PEG NPs also induced nuclei fragmentation and apoptosis in the treated cancer cells [122]. Other NPs which were reported to induce apoptosis in cancer cells are Nos-mPEG-PLGA NPs [117], NVA polymeric NPs [136], ANZ-PLNP NPs [118], 3A.1-loaded pH-sensitive NPs [132], CS-CPT-NPs [133], 5FU-Chrysin-PLGA-PEG-PLGA NPs [120], and Gemcitabine-loaded NPs conjugated with linoleic acid [143]. Nos-mPEG-PLGA NPs [117] has antiangiogenic properties while NVA polymeric NPs [136] inhibited cellular proliferation.…”

“…Naringenin-loaded hyaluronic acid decorated PCL NPs also facilitated drug delivery in NSCLC cells [142]. Gemcitabine (GEM) NPs conjugated with linoleic acid (GEM NPs) have a high drug load, able to control the release of drug, and improve the intracellular uptake in thyroid cancer [143]. DTX-loaded NPs assisted the drug delivery to ovarian cancer [144].…”

Nanomaterials: a promising multimodal theranostics platform for thyroid cancer

“…These nanoparticles could be localized via lysosomes after incubation with differentiated thyroid cancer (DTC) cells and exhibited stronger cytotoxicity to DTC cells than free GEM, promoting apoptosis. 121 Furthermore, nanotechnology can facilitate the delivery of multiple chemotherapeutic drugs and targeted agents in the same nanoparticle, synergistically enhancing the anti-tumor effect. Studies have shown that folate receptor is highly expressed on tumor cell membranes.…”

“…These nanoparticles could be localized via lysosomes after incubation with differentiated thyroid cancer (DTC) cells and exhibited stronger cytotoxicity to DTC cells than free GEM, promoting apoptosis. 121…”

Nanoparticles: Promising Auxiliary Agents for Diagnosis and Therapy of Thyroid Cancers

“…These particles induced apoptosis in follicular thyroid carcinoma FTC133 and in papillary thyroid carcinoma B-CPAP cells. Because the nanoformulations were predicted to damage red blood cells, hemolysis could be excluded in hemolysis assays [83].…”