MRI-Visible Micellar Nanomedicine for Targeted Drug Delivery to Lung Cancer Cells

Abstract

Polymeric micelles are emerging as a highly integrated nanoplatform for cancer targeting, drug delivery and tumor imaging applications. In this study, we describe a multifunctional micelle (MFM) system that is encoded with a lung cancer-targeting peptide (LCP), and encapsulated with superparamagnetic iron oxide (SPIO) and doxorubicin (Doxo) for MR imaging and therapeutic delivery, respectively. The LCP-encoded MFM showed significantly increased αvβ6-dependent cell targeting in H2009 lung cancer cells over a scrambled peptide (SP)-encoded MFM control as well as in an αvβ6-negative H460 cell control. 3H-Labeled MFM nanoparticles were used to quantify the time- and dose-dependent cell uptake of MFM nanoparticles with different peptide encoding (LCP vs SP) and surface densities (20% and 40%) in H2009 cells. LCP functionalization of the micelle surface increased uptake of the MFM by more than 3-fold compared to the SP control. These results were confirmed by confocal laser scanning microscopy, which further demonstrated the successful Doxo release from MFM and accumulation in the nucleus. SPIO clustering inside the micelle core resulted in high T2 relaxivity (>400 Fe mM−1 s−1) of the resulting MFM nanoparticles. T2-weighted MRI images showed clear contrast differences between H2009 cells incubated with LCP-encoded MFM over the SP-encoded MFM control. An ATP activity assay showed increased cytotoxicity of LCP-encoded MFM over SP-encoded MFM in H2009 cells (IC50 values were 28.3 ± 6.4 nM and 73.6 ± 6.3 nM, respectively; p < 0.005). The integrated diagnostic and therapeutic design of MFM nanomedicine potentially allows for image-guided, target-specific treatment of lung cancer.

Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers

“…94 The development of multifunctional magnetic nanoparticle formulations further boosts the potential use of SPIONs in medicine. These formulations not only serve the purpose of being drug delivery vectors but also have applications in MRI imaging, 95 targeted thermosensitive chemotherapy, 96 magnetically targeted photodynamic therapy, 97 and fluorescent/luminescence imaging. 98 Yallapu et al developed water-dispersible SPIONs for hyperthermia, MRI, and drug delivery applications.…”

Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

“…If achieved, magnetic particle biodistribution could be quantitated by conventional MRI and reflect the targeting ability of the ligand-coated particle to bring ARVs to reservoirs of viral infection. 12,13 As a secondary step toward realizing this goal, folic acid (FA)-coated SMART (FSMART) particles were developed. FA has emerged as an important targeting moiety capable of specific interaction with cells, notably mononuclear phagocytes (MPs) (monocytes, macrophages, and dendritic cells), expressing the folate receptor (FR).…”

Nanotheranostics &ndash; a review of recent publications

“…For instance, Guthi and coworkers 32 reported a successful development of prototype on a multifunctional polymeric micelle system in which superparamagnetic IONPs and DOX were encapsulated in the micelle core for MRI and therapeutic delivery, respectively, wherein the micelle surface was functionalized with a lung cancer-targeting peptide (LCP). Amphiphilic block copolymers, maleimide-terminated PEG-co-poly(d-, l-lactic acid) (Mal-PEG-PLA) and methoxy-terminated PEG-co-poly(d-, l-lactic acid) (MeO-PEG-PLA) were synthesized as the micelle core, taken with an incorporation of superparamagnetic IONPs, to exhibit superb T2 relaxivity (.400 Fe mM -1 s -1 ) for ultrasensitive MR detection.…”