Syntheses of polyrotaxane conjugated with 5-fluorouracil and vitamins with improved antitumor activities

Abstract

New antitumor active polyrotaxanes, presynthesized from β-cyclodextrin and polypropylene glycol, were first end capped with antitumor active drug, 5-fluorouracil, and further conjugated with 5-fluorouracil and various bioactive vitamin derivatives such as succinyl vitamin B 2 (PRTVB 2) and ascorbic acid 6-palmitate (PRTASP). FT-IR, 1 H, and 13 C-NMR spectroscopies and elemental analysis were used to characterize the synthesized polyrotaxane and degree of 5-fluorouracil/ vitamins substitution to β-cyclodextrin. The in vitro cytotoxicities of polyrotaxane conjugates were evaluated with mouse mammary carcinoma (FM3A), mouse leukemia (P388), human histiocytic lymphoma (U937) as cancer cell lines, and mouse liver cells (AC2F) as a normal cell line. The cytotoxicities of the polyrotaxane-ascorbic acid conjugates against AC2F normal cell line decreased more than 18,000% as compared with those of 5-fluorouracil. The in vivo antitumor activities of synthesized 5-fluorouracil-1-acetic acid-polyrotaxane (5-FUA-PRT) against mice bearing sarcoma 180 tumor cell line were greater than of 5-fluorouracil at concentration of 800 mg/kg.

Supermolecule—Drug Conjugates Based on Acid-Degradable Polyrotaxanes for pH-Dependent Intracellular Release of Doxorubicin

“…In another example, Wu and Jiang et al developed paclitaxel-conjugated PRXs featuring hydrolyzable ester linkages and validated that the conjugates preferentially accumulated in tumor tissue and exhibited superior antitumor effects compared to free paclitaxel [ 20 ]. Additionally, the terminal ends of axle polymers have been utilized to conjugate anticancer drugs and other functional molecules, such as imaging agents [ 21 , 22 , 23 ]. These studies suggest that PRXs have significant potential as an emerging platform for drug delivery systems (DDSs).…”

Fabrication and Biological Activities of Plasmid DNA Gene Carrier Nanoparticles Based on Biodegradable l-Tyrosine Polyurethane

“…These properties of LTU make it promising for gene delivery applications that require the sustained release of DNA throughout the entire lifetime of the cell. In contemporary years, a number of our previous research studies have been applied to develop biodegradable nanoparticles based on aliphatic polyester, poly(amino acid), polyanhydride, and biopolymer and used to evaluate their biological activities and cytotoxicities as antitumoral and antibacterial agents, and as gene carriers [14][15][16].…”

“…Ideally, the carriers used in non-viral gene therapy should be able to deliver the encapsulated genetic material to the targeted location in cells and into the nucleus of the cell without causing toxicity or eliciting an immune response. For efficient uptake into cells, non-viral delivery carriers must be of an appropriate size for endocytosis, following which they are degraded in the body to prevent toxicity due to carrier accumulation, and thus, they should be able to release the genetic material before the cell death in order to achieve a high delivery efficiency [15,19]. To improve the relatively low transfer efficiency compared to the commonly used viral vectors, plasmid DNA (pDNA)-linear polyethylenimine (LPEI) was used as a complex with DNA, and its surface was modified with PEG using the double emulsion method.…”

Synthesis and Characterization of Polyfumarateurethane Nanoparticles for Sustained Release of Bupivacaine

“…Biodegradable polymer was designed to have an ester group on its backbone to allow its degradation into biocompatible diacids and diols [15][16][17][18][19][20]. We also previously reported a number of studies on the synthesis of biodegradable polymers based on aliphatic polyester, polyanhydride, poly(amino acid), biopolymer and their in vitro and in vivo cytotoxicities-after antitumor, antibacterial, gene-delivered nanoparticles were fabricated [21][22][23][24][25][26][27].…”