Biotin anchored nanostructured lipid carriers for targeted delivery of doxorubicin in management of mammary gland carcinoma through regulation of apoptotic modulator
Authors: Poonam Parashar
Shubhini A Saraf
Jovita Kanoujia
Chandra B Tripathi
Malti Arya
Mahendra Singh
Gaurav Kaithwas
Journal: Journal of liposome research (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Apoptosis; MCF-7 Cell lines; flow cytometry; immunoblotting; nanostructured lipid carriers.
Affiliations: Department of Pharmaceutical Sciences, School of Biosciences & Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Lucknow, India.

Abstract:  Mammary gland tumour has the highest incidence rate and mortality in women, worldwide. The present study envisaged a molecularly targeted nanostructured lipid carrier (NLCs) for doxorubicin (Dox) delivery capable of inducing cellular apoptosis in mammary gland tumour. NLCs were prepared utilizing Perilla frutescens oil (54-69% ω3-fatty acid) as liquid lipid to enhance entrapment of Dox through molecular ion pairing. Biotin decorated NLCs (b-Dox-NLCs) were evaluated in vitro and in vivo. The b-Dox-NLCs showed particle size of 105.2 ± 3.5 nm, zeta potential -35 ± 2 mV, entrapment 99.15 ± 1.71%, drug content 19.67 ± 2.6 mg.g-1, biotin content 5.85 ± 0.64 µg.g-1 and drug release 98.67 ± 2.43% (facilitated by acidic microenvironment) respectively. MTT assay and Flow cytometric analysis revealed higher anti-proliferative capability of b-Dox-NLCs to force apoptosis in MCF-7 cell line vis-à-vis marketed Dox, evidenced by reactive oxygen species level and mitochondrial membrane potential mediated apoptosis. Enhanced antitumor targeting, therapeutic safety and efficacy was exhibited by b-Dox-NLCs, as investigated through tumour volume, animal survival, weight variation, cardiotoxicity and biodistribution studies in 7,12-Dimethylbenz[a]anthracene induced mammary gland tumour. Immunoblotting assay demonstrated b-Dox-NLCs downregulated anti-apoptotic proteins, i.e. bcl-2, MMP-9 while upregulated pro-apoptotic proteins, i.e. caspase-9, p16 and BAX. The experimental results suggest that biotinylated ω3-fatty acid augmented NLCs loaded with Dox are capable of inducing programmed cell death in mammary tumour and can be utilized as safe and effective delivery system with enhanced potential for mammary gland carcinoma therapy. 

Retracted: No

PubPeer comments:
 Image below apparently refers to 7 different treatment groups, but in one case, three of the images appear to overlap (green) and in another two of the images appear to overlap (orange). I believe these are from Figure 8 described in this paragraph: There was significant increase in the number of AB TEB, demonstrating the cellular proliferation in the mammary gland as observed in carmine stain of toxic group. The treated groups presented significant defence against cellular proliferation on DMBA treatment. The effect of Dox-NLCs and b-Dox-NLCs was more pronounced in lowering the AB TEBs count (Fig. 8). Similar inference can be withdrawn from the H E staining of mammary gland tissues of the groups represented through ducts, adipocytes, LCT, DCT and tissue architecture. Treatment with NLC formulations showed different degree of restoration of cellular architecture closer to control group. **** ![file] , 
 ImageTwin found an additional overlap between group I and group VI (orange box below). *** ![file] , 
 ImageTwin also identified a previous paper which included one of these images from Figure 8, where it seems to have been described differently. There seems to be at least one common author on the two papers. Figure 1, BMC Complementary and Alternative Medicine (2016), doi: 10.1186 s12906-016-1243-5 *** ![file] , 
 ImageTwin also identified a previous paper which included another an image which overlaps with one the images from Figure 8 (cropped differently and aspect ratio changed). There seems to be at least one common author on the two papers. Figure 6, Oncotarget (2017), doi: 10.18632 oncotarget.19551 *** ![file] ,