Nanosized carriers based on amphiphilic poly-N-vinyl-2-pyrrolidone for intranuclear drug delivery (original) (raw)

Aim: Ability to deliver drugs into the cell nuclei can significantly increase the efficacy of cancer therapies, in particular in the case of multidrug-resistant cancer Results: Polymer nanocarriers based on amphiphilic thiooctadecyl-terminated poly-N-vinyl-2-pyrrolidone were produced and loaded with a model hydropho-bic drug, curcumin. Two commonly used loading approaches-emulsification and ultrasonic dispersion-were found to lead to two different size distributions with distinctively different biological effect. While nanocarriers produced via the emulsion method penetrated cells by dynamin-dependent endocytic mechanisms , sub-100 nm dispersion-produced nanocarriers were capable of crossing the membranes via biologically independent mechanisms. Conclusion: This finding opens an intriguing possibility of intranuclear delivery by merely tailoring the size of polymeric carriers, thus promising a new approach for cancer therapies. Keywords: atomic force microscopy • curcumin • fluorescence microscopy • intranuclear drug delivery • nanocarrier • PVP Nanoformulated drug-delivery systems based on various nanoncarriers-liposomes, micelles, nanoparticles, etc.-are rapidly becoming the mainstream approach in medicine, in particular, cancer therapy. They offer a number of advantages compared with systemical application of drugs, including prolonged circulation time, ability of cell-specific targeting through passive and active mechanisms, and controlled drug release [1]. As a result, nanocarriers protect their cargo from degradation, increase the efficacy of drugs and reduce toxicity to healthy tissue and hence unwanted side effects. Since most of the anticancer drugs attack cell DNA, the ability to penetrate cell nuclei can significantly increase the therapeutic efficacy. This becomes particularly important for treatment of multidrug-resistant cancer, since low molecular drug released in cytoplasm can be still cleared of the multidrug-resistant cells [2]. Cellular uptake of nanoparticle carriers usually occurs through endocytic pathways [3,4]. Briefly, a particle that comes into contact with the cell exterior becomes engulfed by the cell membrane, forming an invagination, which afterward separates from the membrane as a vesicle and transports its cargo to various intracellular destinations. Most of the time, particles are treated by the cell as foreign objects and transported to lysosomes causing degradation Nanomedicine (Lond.) (2018) 13(7), 703-715