Long Circulating Lectin Conjugated Paclitaxel Loaded Magnetic Nanoparticles: A New Theranostic Avenue for Leukemia Therapy

Abstract

Amongst all leukemias, Bcr-Abl positive chronic myelogenous leukemia (CML) confers resistance to native drug due to multi drug resistance and also resistance to p53 and fas ligand pathways. In the present study, we have investigated the efficacy of microtubule stabilizing paclitaxel loaded magnetic nanoparticles (pac-MNPs) to ascertain its cytotoxic effect on Bcr-Abl positive K562 cells. For active targeted therapy, pac-MNPs were functionalized with lectin glycoprotein which resulted in higher cellular uptake and lower IC50 value suggesting the efficacy of targeted delivery of paclitaxel. Both pac-MNPs and lectin conjugated pac-MNPs have a prolonged circulation time in serum suggesting increased bioavailability and therapeutics index of paclitaxel in vivo. Further, the molecular mechanism pertaining to pac-induced cytotoxicity was analyzed by studying the involvement of different apoptotic pathway proteins by immunoblotting and quantitative PCR. Our study revealed simultaneous activation of JNK pathway leading to Bcr-Abl instability and the extrinsic apoptotic pathway after pac-MNPs treatment in two Bcr-Abl positive cell lines. In addition, the MRI data suggested the potential application of MNPs as imaging agent. Thus our in vitro and in vivo results strongly suggested the pac-MNPs as a future prospective theranostic tool for leukemia therapy.

Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery

“…28 These results indicated that XNMs possessed a higher efficiency in drug delivery into A2780 cells than that of LNMs. Comparing the structures of polymers that formed LNMs and XNMs as well as their physicochemical characteristics, this cellular uptake enhancement might be attributed to the smaller particle size of XNMs.…”

“…cellular uptake study Cellular uptake efficiency of coumarin 6-loaded nanomicelles (C6/XNMs and C6/LNMs) were conducted on A2780 cells using flow cytometry. 28 Typically, approximately 8,000 cells were seeded in each well of a 12-well plate and incubated overnight. The DMSO solution of coumarin 6 and coumarin 6-loaded nanomicelles was diluted in medium to get a concentration of 50 ng/ mL of coumarin 6.…”

Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges

“…40 As such, lectins, such as wheat germ agglutinin (WGA), may be employed for targeting of NPs for cancer imaging or therapy. Despite the extensive applications of lectin-NP conjugates in investigating the glycan-NP interactions, 41 there is only a small number of studies using lectin-functionalized NPs for imaging applications.…”

Current perspectives on the therapeutic aspects of chronic myelogenous leukemia

“…In another study, paclitaxel-loaded magnetic nanoparticles (pac-MNPs) and lectin-conjugated pac-MNPs were found to have prolonged the circulation time in rat serum which indicated enhanced bioavailability and thus the therapeutic potential of paclitaxel. The treatment with the drug resulted in the arrest of the cells at G2-M phase and the paclitaxel-loaded nanoparticles mediated the cell death by activating the extrinsic and intrinsic pathways of apoptosis [77].…”