Lx2-32c–loaded polymeric micelles with small size for intravenous drug delivery and their inhibitory effect on tumor growth and metastasis in clinically associated 4T1 murine breast cancer

Abstract

Lx2-32c is a novel taxane derivative with a strong antitumor activity. In this study, we developed Lx2-32c–loaded polymeric micelles (Lx2-32c-PMs) with small size and investigated their antitumor efficacy against tumor growth and metastasis on 4T1 murine breast cancer cell line with Cremophor EL–based Lx2-32c solution as the control. In this study, copolymer monomethoxy polyethylene glycol 2000 –polylactide 1300 was used to prepare Lx2-32c-PMs by film hydration method, and their physicochemical properties were characterized as well, according to morphology, particle size, zeta potential, in vitro drug release, and reconstitution stability. Under confocal laser scanning microscopy, it was observed that Lx2-32c-PMs could be effectively taken up by 4T1 cells in a time-dependent manner. Cell Counting Kit-8 assay showed that the IC 50 of Lx2-32c-PMs was 0.3827 nM. Meanwhile, Lx2-32c-PMs had better ability to promote apoptosis and induce G 2 /M cycle block and polyploidy formation, compared with Lx2-32c solution. More importantly, in vivo animal studies showed that compared to Lx2-32c solution, Lx2-32c-PMs possessed better ability not only to effectively inhibit the tumor growth, but also to significantly suppress spontaneous and postoperative metastasis to distant organs in 4T1 orthotopic tumor-bearing mice. Consequently, Lx2-32c-PMs have significantly prolonged the survival lifetime of tumor-bearing mice. Thus, our study reveals that Lx2-32c-PMs had favorable antitumor activity and exhibited a good prospect for application in the field of antitumor therapy.

<p>Improving the anti-keloid outcomes through liposomes loading paclitaxel&ndash;cholesterol complexes</p>

“…HKFs were inoculated in a plate with 96 wells and adjusted to 5.0×10 3 cells/well. After 24 hours' culture, the primary medium was replaced with the fresh medium containing a series of different test samples for another 24…”

“…Despite its efficacy in various diseases, PTX solvent used clinically contains a high concentration of Kolliphor EL (BSAF Company, Rheinland-Pfalz, German), 24 which can result in severe allergic reactions in patients. New drug delivery systems have been exploited to avoid hypersensitivity, eg, micelles, hydrogel, cyclodextrin nanocarriers, and liposomes.…”

<p>Improved Antitumor Outcomes for Colon Cancer Using Nanomicelles Loaded with the Novel Antitumor Agent LA67</p>

“…27,28,37,38 In our previous study, we prepared docetaxel-loaded and Lx2-32c-loaded polymeric micelles. 39,40 Our results showed that polymeric micelles were stable and effective vectors for antitumor drugs.…”

“…Polymeric micelles containing LA67 were prepared using a film hydration method. 40 Briefly, 3 mg of LA67 and 150 mg of mPEG 2000 -PLA 1300 were dissolved in 3 mL of acetonitrile. Then, acetonitrile was removed by rotary evaporation in a water bath (50°C for 40 min).…”

“…Coumarin-6 is a relatively stable fat-soluble fluorescent dye, which is often encapsulated in nano-drug delivery systems to study mechanisms of intracellular uptake and transport. 40,49 Coumarin-6-stained nuclei showed green fluorescence signals (Figure 4A). After incubation with C6-PMs for 5 min, the green fluorescence signal was detected.…”