Assessment of Intracellular Delivery Potential of Novel Sustainable Poly(δ-decalactone)-Based Micelles

Abstract

Biodegradable polymers from renewable resources have attracted much attention in recent years within the biomedical field. Lately, poly(δ-decalactone) based copolymer micelles have emerged as a potential drug delivery carrier material as a sustainable alternative to fossil-based polymers. However, their intracellular drug delivery potential is not yet investigated and therefore, in this work, we report on the synthesis and cellular uptake efficiency of poly(δ-decalactone) based micelles with or without a targeting ligand. Folic acid was chosen as a model targeting ligand and Rhodamine B as a fluorescent tracer to demonstrate the straightforward functionalisation aspect of copolymers. The synthesis of block copolymers was accomplished by a combination of facile ring-opening polymerisation and click chemistry to retain the structure uniformity. The presence of folic acid on the surface of micelles with diameter ~150 nm upsurge the uptake efficiency by 1.6 fold on folate receptor overexpressing MDA-MB-231 cells indicating the attainment of targeting using ligand functionality. The drug delivery capability of these carriers was ascertained by using docetaxel as a model drug, whereby the in vitro cytotoxicity of the drug was significantly increased after incorporation in micelles 48 h post incubation. We have also investigated the possible endocytosis route of non-targeted micelles and found that caveolae-mediated endocytosis was the preferred route of uptake. This work strengthens the prospect of using novel bio-based poly(δ-decalactone) micelles as efficient multifunctional drug delivery nanocarriers towards medical applications.

Stimuli-Responsive, Plasmonic Nanogel for Dual Delivery of Curcumin and Photothermal Therapy for Cancer Treatment

“…One day later, the cell media was substituted by fresh media containing AuNP (20 μg/ml), nanogel (100 μg/ml), and AuNP@Ng (120 μg/ml) and incubated at 37°C, 5% CO 2 for 24 h ( n = 3). Afterwards, cells were harvested with trypsinization, washed twice with ice cold PBS and resuspended in 250 μl of PBS, kept on ice until analysis (Bansal et al, 2020 ). Mean fluorescence intensity was recorded by using a 561 nm excitation laser and the emission was collected by using RFP 582/15 band pass filter with LSRFortessa (BD Sciences, San Diego, CA, USA).…”

Synthesis and Evaluation of Novel Functional Polymers Derived from Renewable Jasmine Lactone for Stimuli‐Responsive Drug Delivery

“…Close to neutral surface charge was expected from PJL‐DOX micelles owing to the PEG corona where the micelles are usually sterically stabilized instead of electrostatically. [ 3,5 ] The in vitro drug release was performed via dialysis method at pH 5.0 mimicking intracellular environment in the presence of two different concentrations of commonly used reducing agent dithiothreitol (DTT). [ 21 ] A sustained release pattern was observed for DOX from PJL‐DOX micelles and as expected, a higher percentage of the drug was released in the presence of elevated DTT concentration (Figure 2F).…”

“…PDL‐based drug delivery carriers were evaluated largely for their toxicity, biodegradability, and their potential as drug delivery carriers. [ 3–6 ]…”

Methylene blue associated with maghemite nanoparticles has antitumor activity in breast and ovarian carcinoma cell lines

“…Previous studies have demonstrated the uptake of IONs by endocytic pathway in various cell types (Calero et al 2015;Saadat et al 2019;Zavisova et al 2018;Youhannayee et al 2018). To elucidate the endocytic pathway, we performed a cytometry analysis to evaluate the cells after treatment with the pathway inhibitors and MAGCIT-MB (0.78 µg mL −1 for 6 h) (Rodrigues et al 2020;Bansal et al 2020). The results demonstrated that all cells have a statistically significant result for the inhibitor phenylarsine oxide.…”