Theranostic tumor homing nanocarriers for the treatment of lung cancer

Abstract

The drugs/strategies to selectively inhibit tumor blood supply has generated interest in recent years for enhancement of cancer therapeutics. The objective of this study was to formulate tumor homing PEGylated CREKA peptide conjugated theranostic nanoparticles of DIM-C-pPhC6H5 (DIM-P) and investigate in vivo antitumor activity as well as evaluate the targeted efficiency to lung tumors using imaging techniques. DIM-P loaded Nanoparticles (NCs-D) were prepared using lipids, and DOGS-NTA-Ni and the surface of NCs-D was modified with PEGylated CREKA peptide (PCNCs-D). PCNCs-D showed 3 fold higher binding to clotted plasma proteins in tumor vasculature compared to NCs-D. PCNCs-D showed 26±4% and 22±5% increase in tumor reduction compare to NCs-D in metastatic and orthotopic models respectively. In-vivo imaging studies showed ~40 folds higher migration of PCNCs-Di in tumor vasculature than NCs-Di. Our studies demonstrate the role of PCNCs-D as theranostic tumor homing drug delivery and imaging systems for lung cancer diagnosis and treatment.

Evaluation of Spray BIO-Max DIM-P in Dogs for Oral Bioavailability and in Nu/nu Mice Bearing Orthotopic/Metastatic Lung Tumor Models for Anticancer Activity

“…Pharmacokinetic data analysis: Pharmacokinetic analysis (DIM-P extraction, HPLC analysis and parameters) were determined as described earlier using non-compartmental techniques (2,22,23). …”

“…Also, TUNEL assay, IHC for VEGF expression and Western blot analysis of lung tumor tissues were carried out as described earlier (23). …”

Understanding and exploiting nanoparticles' intimacy with the blood vessel and blood

“…For instance, the bulk of nanomedicine strategies for cancer treatment [117][118][119][120] were tested against ECs derived from human umbilical vein endothelium (HUVEC), which possesses no structural and biomarker expression resemblance to the tumor ECs nor any close relevance to adult ECs since umbilical endothelium is only present at a specific stage of an adult life; during pregnancy. For instance, the bulk of nanomedicine strategies for cancer treatment [117][118][119][120] were tested against ECs derived from human umbilical vein endothelium (HUVEC), which possesses no structural and biomarker expression resemblance to the tumor ECs nor any close relevance to adult ECs since umbilical endothelium is only present at a specific stage of an adult life; during pregnancy.…”

Novel therapeutic approaches for pulmonary arterial hypertension: Unique molecular targets to site-specific drug delivery

“…Targeted delivery of the pharmaceuticals has been well established by various researchers via both systemic and respiratory routes for an assortment of malignant lung disorders including small cell lung cancer (SCLC) utilizing active monoclonal antibody targeting approach for both therapeutic efficacy and for diagnostic visualization [93][94][95][96]. At the same time, several groups have studied gene targeting as a treatment approach for cystic fibrosis [97][98][99].…”